Paroxysmal nocturnal hemoglobinuria: Treatment landscape and payer management Nonalcoholic steatohepatitis: First approval and payer strategies
Anti-obesity update: Increased utilization of GLP-1 agonists and management
Artificial intelligence: Opportunities for health care application
Pulmonary arterial hypertension: Exciting new approval and payer impact
September 16–18, 2024
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Magellan Rx Management | Prime Therapeutics 2900 Ames Crossing Road Eagan, MN 55121 magellanrx.com
Editor
Lindsay Speicher, J.D. Project Manager, Specialty lindsay.speicher@primetherapeutics.com
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Lindsay Speicher, J.D. lindsay.speicher@primetherapeutics.com
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The content of Magellan Rx™ Report — including text, graphics, images and information obtained from third parties, licensors and other material (“content”) — is for informational purposes only. The content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Magellan Rx™ Report does not verify any claims or other information appearing in any of the advertisements contained in the publication and cannot take responsibility for any losses or other damages incurred by readers in reliance on such content. Developed by D Custom.
Contributors
Steve Cutts, Pharm.D. SVP, Market General Manager, MRx Specialty
Haita Makanji, Pharm.D. VP, Clinical Strategy and Innovation, Specialty
Amy E. Edquist Senior Manager, Marketing
Joe Tavares SVP, Sales and Business Development, Specialty
Simone Ndujiuba, Pharm.D., BCOP Director, Clinical Strategy and Innovation, Oncology
Carole Kallas Project Manager
Brian MacDonald, Pharm.D. Director, Specialty Clinical Strategy
Alina Young Associate Legal Counsel
Editorial Advisory Board
Mona M. Chitre, Pharm.D., CGP
Chief Pharmacy Officer & VP Clinical Analytics, Strategy & Innovation, Excellus BlueCross BlueShield
Dennis Bourdette, M.D., FAAN, FANA
Chair and Roy and Eulalia Swank Family Research Professor, Department of Neurology, Oregon Health & Science University
Yousaf Ali, M.D., FACR Chief, Division of Rheumatology, Mount Sinai West; Professor of Medicine, Icahn School of Medicine at Mount Sinai
Steven L. D’Amato, B.S.Pharm. Executive Director, New England Cancer Specialists
Joseph Mikhael, M.D., M.Ed., FRCPC, FACP Chief Medical Officer, International Myeloma Foundation
Steve Marciniak, R.Ph.
Director II, Medical Benefit Drug Management, Blue Cross Blue Shield of Michigan
Saira A. Jan, M.S., Pharm.D. Director of Pharmacy Strategy and Clinical Integration, Horizon Blue Cross Blue Shield of New Jersey
Dear managed care colleagues,
Prime Therapeutics and Magellan Rx (Prime and Magellan Rx) are excited to bring you our summer 2024 issue of the Magellan Rx Report! 2024 has been an exciting year full of promising new treatment opportunities, with 16 novel drug approvals so far and an expansive pipeline for the remainder of the year. As always, Prime and Magellan Rx are dedicated to bringing our readers valuable updates in managed care trends.
This issue’s cover story (Page 11) explores exciting treatment advances in pulmonary arterial hypertension (PAH), including the first approval of a therapy indicated for PAH. We address how payers may focus and strategize in this category.
In our anti-obesity update article (Page 24), we highlight the recent increased utilization of GLP-1 agonists and proper management of this class. As more GLP-1 treatments become indicated for weight management, it will becoming increasingly important for payers to control costs and ensure appropriate access in order to properly manage these therapies.
Another article (Page 16) focuses on new updates in nonalcoholic steatohepatitis (NASH). Prior to 2024, there were no U.S. Food and Drug Administration-approved therapies for NASH. Here, we outline the first approval in this space and explore how it may disrupt or impact payer management of this population.
Other topics in this issue include a discussion of paroxysmal nocturnal hemoglobinuria (Page 6), an exploration of the changing multiple sclerosis landscape (Page 20), a brief on artificial intelligence in health care (Page 28), a feature on CMS Star Ratings (Page 30) and an update on the impact of the Inflation Reduction Act (Page 42). As always, we’ve rounded out the issue with our pipeline update (Page 48) and managed care newsstand (Page 4).
To learn more about our support for payer initiatives of the future, please feel free to contact us at lindsay.speicher@ primetherapeutics.com. As always, we value any feedback you may have. I hope you enjoy the report!
Sincerely,
Steve Cutts, Pharm.D., R.Ph. Senior Vice President, Specialty & Clinical Solutions Prime Therapeutics
Stay on top of managed care trends and become a Magellan Rx Report subscriber. Email us at PTReport@primetherapeutics.com to subscribe today. Magellan Rx Report provides pharmacy and medical management solutions for managed care executives and clinicians. We hope you enjoy the issue; thank you for reading.
Long-standing bicameral, bipartisan federal legislation The Treat and Reduce Obesity Act (TROA) (H.R. 4818/S. 2407) would allow Medicare Part D to cover drugs used for treatment of obesity or weight loss management. Kaiser Family Foundation analysis found that about 7% of Medicare beneficiaries, or 3.6 million people, may qualify for Wegovy® coverage for its cardiovascular indication and that this coverage could cost the Medicare Part D program $2.8 billion in a single year.
The key determinant is the Congressional Budget Office (CBO) score. The CBO head said the net costs of the drug would have to drop by 90% to even “get in the ballpark” of not increasing the national deficit. CBO is still studying the impact of medications that treat obesity, but there are congressional efforts to get CBO to rethink how it scores prevention, including obesity drugs. CBO predicted that semaglutide would be selected for Medicare price negotiation within the next few years.
In April, HELP Committee Chairman Bernie Sanders (I-VT) launched an investigation into the price of Wegovy and Ozempic®, including information on the net price and the five largest PBMs Novo Nordisk contracts with. The Federal Trade Commission (FTC) challenges the validity of some Ozempic patents, which could speed the introduction of generic alternatives.
This legislation would limit patient costsharing for patients receiving non-opioid pain relief to no greater than generic tier under Medicare Part D plans. Additionally, the use of step therapy and prior authorization (PA) would be prohibited for these drugs. This legislation has not been subject to any hearings and is not likely to move this Congress, but it is likely to return in 2025.
The Final Rate makes updates to the Inflation Reduction Act (IRA) for 2025 including Part D redesign coverage phases (i.e., elimination of coverage gap) and $2,000 out-of-pocket cap. The Centers for Medicare and Medicaid Services (CMS) will update the Part D Risk Adjustment Model in CY2025, which will result in an increase in plan liability due to the $2k out-ofpocket cost cap. There are also changes to the true out-of-pocket costs (TrOOP). Additionally, there are separate risk score normalization factors for MAPDs and PDPs. CMS is considering revising the creditable coverage definition. The methodology for specialty tier threshold is updated.
In April, CMS issued the CY2025 MA and Part D final rule, which allows flexibility to more quickly substitute biosimilar products for their reference products as well as updated criteria for the Part D Medication Therapy Management (MTM) program. The rule requires plans to update composition and responsibility of the
When there is potentially noncompliant activity or discriminatory benefit design, OCR will apply a factspecific assessment on a case-by-case basis to determine liability.
utilization management (UM) committee (e.g., include health equity experts and annual report on health equity analysis of PA policies).
In April, the Nondiscrimination in Health Programs and Activities final rule was published. It included newly codified protections in 1557 that apply to any health care program, service or activity that receives federal funding (e.g., provider under a Medicare agreement or supplier that receives Medicare payments). The rule applies to third-party administrators (TPAs) and PBMs that receive federal financial assistance or are part of another covered entity’s operations. When there is potentially noncompliant activity or discriminatory benefit design, OCR will
apply a fact-specific assessment on a caseby-case basis to determine liability.
In May, the Medicare Drug Price Negotiation Program Draft Guidance for 2027 was made public and outlines new requirements for a second cycle of negotiation, which begins in 2025 and will result in Maximum Fair Prices (MFPs) effective for 2027. The guidance sets forth additional policies regarding manufacturer effectuation of the MFP in 2026 and 2027, including the use of a Medicare Transaction Facilitator (MTF) to facilitate the exchange of data and payment between pharmaceutical supply chain entities (e.g., proposing two options for MTF operations).
Congress passed two spending packages in March to fund the government for the rest of the fiscal year 2024 and avert a government shutdown. Neither the March 8 nor March 22 packages included PBM-related policies. Despite widespread bicameral, bipartisan support for PBM reform, the scope and whether PBM policies should apply to the commercial market or only federal program was a major sticking point for lawmakers. A narrowly divided makeup in both chambers put pressure on congressional leadership to keep the packages free of controversial items and avoid opening them up to a wide range of issues unrelated to expiring provisions or funding.
The next big push to pass PBM legislation is expected during the lame duck session after the November elections. However, lawmakers could attempt to pass PBM reform any time before the lame duck.
On March 14, Senate Finance Chair Ron Wyden (D-OR) and Ranking Member Mike Crapo (R-ID) held a press conference with pharmacists urging Congress to pass two PBM reform bills that advanced in their committee last year. One bill, the Modernizing and Ensuring PBM Accountability (MEPA) Act, would prohibit spread pricing in Medicaid and impose additional PBM drug pricing transparency. The other, the Better Mental Health Care, Lower-Cost Drugs and Extenders Act, includes the No PBMs Act and requires CMS to define reasonable and relevant contract terms in Medicare.
Senate and House members call for leadership to act immediately to pass PBM legislation
On March 15, 21 Senators and 51 House members sent a letter to Senate Majority Leader Chuck Schumer (D-NY) and Minority Leader Mitch McConnell (R-KY) to call for immediate action on enacting PBM reforms.
On March 4, the White House convened a roundtable on “Lowering Healthcare Costs and Bringing Transparency to Prescription Middlemen.” The panelists included senior officials from across the administration as well as leaders from state government, the private sector and community pharmacies. Panelists scrutinized PBM practices focusing on spread pricing, takeit-or-leave-it contracts and alleged lack of transparency.
On March 11, President Biden released his proposed budget for the fiscal year 2025. While the proposal is unlikely to pass a divided Congress, it reflects the administration’s policy priorities. The budget proposes limiting Medicare Part D cost-sharing for high-value generic drugs to no more than $2 for Medicare beneficiaries. The president also wants Congress to expand certain IRA provisions, including extending both the $2,000 annual cap on Medicare prescription drugs and Part D drug inflation rebates to the commercial market. During his State of the Union address, President Biden proposed expanding drug price negotiations to at least 50 drugs per year. The current law allows up to 20 drugs per year.
President Biden launches strike force on unfair and illegal pricing
On March 5, President Biden announced a joint task force to crack down on unfair and illegal pricing in specific industries, including prescription drugs and health care. The task force will be co-chaired by the Department of Justice and FTC and is another indication of the administration’s commitment to easing patients’ drug costs and curbing anti-competitive business practices.
Brian MacDonald, Pharm.D. Senior Manager, Clinical Strategy and Innovation Magellan Rx Management
An acquired hematopoietic stem cell disorder, paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder in which red blood cells break apart prematurely.1 PNH is caused by a genetic mutation in the PIG-A gene of a single stem cell in the bone marrow.2 In individuals with PNH, some hematopoietic stem cells (HSCs) are defective and produce defective blood cells, which are extremely susceptible to premature destruction, or hemolysis, by the complement system.1 This can lead to episodes of hemoglobin in the urine, or hemoglobinuria.1 Hemolysis is a constant process in those with PNH, although hemoglobin in the urine may not always be visible.1 People with PNH are also susceptible to developing repeated, potentially life-threatening blood clots, or thromboses, as well as underlying bone marrow dysfunction.1 In severe bone marrow dysfunction cases, pancytopenia, or low levels of red and white blood cells, can occur.1
The only known risk for developing PNH is having aplastic anemia.2 More than 10% of people with aplastic anemia will develop PNH, and some people with PNH will subsequently develop aplastic anemia.2 Furthermore, 2% of patients with PNH go on to develop myelodysplastic syndrome (MDS).2
Eculizumab (Soliris®), which binds to proteins in the blood that can destroy red blood cells, thus reducing the risk of blood clotting and improving quality of life, is the most widely used drug therapy for PNH.3 Ravulizumab (Ultomiris®), another commonly used PNH therapy, works similarly to eculizumab.3 Eculizumab and ravulizumab are both intravenously infused C5 inhibitors, dosed at every two weeks and every eight weeks, respectively.3 The U.S. Food and Drug Administration (FDA) approved a third drug treatment for PNH, pegcetacoplan (Empaveli®), in 2021. Pegcetacoplan is a C3 inhibitor, selfadministered subcutaneously twice weekly.4
For some patients — including those who do not respond to eculizumab or who have severely reduced red blood cells, white blood cells and platelets — it may be appropriate to undergo a bone marrow transplant to deliver healthy HSCs.3 Providers typically recommend young patients with severe disease and significant marrow failure for this procedure.3
Pegcetacoplan on-body injector (Empaveli Injector)
In September 2023, the FDA approved the pegcetacoplan onbody injector (Empaveli Injector, Apellis Pharmaceuticals) for selfadministration of pegcetacoplan for adult patients with PNH.5 The compact, single-use, on-body injector is the first high-volume, subcutaneous on-body delivery system for pegcetacoplan approved by the FDA. It features a push button to start the injection with a hidden needle that automatically retracts after the dose is given.5
Iptacopan (Fabhalta®)
In December 2023, the FDA approved iptacopan (Fabhalta®, Novartis) for the treatment of adults with PNH.6 This approval marks the first and only FDA-approved Factor B inhibitor of the immune system’s complement pathway.6
Data from the phase 3 APPLY-PNH trial in patients with residual anemia despite prior anti-C5 treatment and the phase 3 APPOINTPNH study in complement inhibitor-naïve patients supported FDA approval.6 APPLY-PNH assessed the efficacy and safety of twice-daily oral iptacopan monotherapy 200 mg with the aim of demonstrating its superiority compared to anti-C5 antibody
treatments eculizumab and ravulizumab in patients with residual anemia despite a prior stable regimen of anti-C5 treatment.7 A total of 97 adult patients were enrolled and randomized in an 8:5 ratio to treatment with twice-daily oral iptacopan or intravenous anti-C5 therapies.7 APPOINT-PNH assessed the efficacy and safety of twice-daily oral iptacopan monotherapy 200 mg in adult patients who were naïve to complement inhibitor therapy. A total of 40 patients were enrolled and received treatment with iptacopan.8
Results from the 24-week core treatment periods in both trials showed that in patients with sustained increase of hemoglobin levels >2 g/dL from baseline in the absence of transfusions, 82.3% of anti-C5-experienced iptacopan patients responded compared to 0% of anti-C5.7, 8 Of the complement inhibitor-naïve patients treated with iptacopan, 77.5% achieved this outcome.7, 8 Additionally, 67.7% of anti-C5-experienced iptacopan patients among those with sustained hemoglobin level >12 g/dL in the absence of transfusions responded compared to 0% of anti-C5 patients.7, 8 The transfusion avoidance rate was 95.2% and 45.7% for anti-C5-experienced iptacopan patients and anti-C5 patients, respectively.7, 8
Post-approval data was released from the APPLY-PNH trial and showed, from baseline to week 48, an adjusted mean increase in hemoglobin of 3.35 g/dL in patients treated with iptacopan
and 3.36 g/dL in those who switched from anti-C5 to iptacopan.9 Meanwhile, the adjusted mean difference in hemoglobin levels from week 24 to week 48 in each respective arm was a decrease of 0.41 g/dL and an increase by 3.02 g/dL.9 Transfusion independence in patients receiving iptacopan was observed in 95.2% from week two to week 24 and in 91.9% from week two to week 48.9 Transfusion independence at week 24 was observed in 40% of those who initially received anti-C5 therapy, and after switching to treatment with iptacopan, it was observed at 94.1% from week 26 to 48.9
Adverse reactions in the APPLY-PNH trial associated with iptacopan were headache, nasopharyngitis, diarrhea, abdominal pain, bacterial infection, nausea and viral infection, while more serious reactions reported in two patients were pyelonephritis, urinary tract infection and COVID-19.6 The most commonly reported adverse reactions associated with iptacopan in the APPOINT-PNH trial were headache, viral infection, nasopharyngitis and rash, while serious reactions reported in two individuals who received iptacopan included COVID-19 and bacterial pneumonia.6
In April 2024, the FDA approved danicopan (Voydeya, AstraZeneca) as an add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with PNH.10 Top-line results from the ALPHA phase 3 trial informed the FDA approval.10 The trial evaluated efficacy and safety of danicopan as an add-on to C5 inhibitor therapy, eculizumab or ravulizumab, in patients with PNH who experience clinically significant EVH.12 A total of 86 patients were randomized to receive danicopan or placebo.12 Trial results showed that danicopan met the primary endpoint of change in hemoglobin from baseline to week 12 and all secondary endpoints, including transfusion avoidance and change in Functional Assessment of Chronic Illness Therapy –Fatigue (FACIT-Fatigue) score.10, 11
After the 12-week randomized control period, significant improvements in hemoglobin levels were observed [LSM (SEM) change 2.94 (0.21) g/dL] and continued at 24 weeks [LSM (SEM) change 3.17 (0.30) g/dL] among those treated with danicopan plus C5 inhibitor and were sustained through 48 weeks.11 All secondary endpoints measured at 24 weeks met superiority in favor of danicopan plus C5 inhibitor compared to placebo plus C5 inhibitor at 12 weeks, and data showed those who initiated on danicopan maintained these benefits in 24 weeks.11 All key secondary endpoints showed meaningful improvement at 24 weeks in patients who switched from placebo to danicopan at 12 weeks.11
In May 2024, the FDA approved eculizumab-aeeb (Bkemv®, Amgen) as the first interchangeable biosimilar to reference eculizumab (Soliris®). The biosimilar is approved to treat two rare diseases, both of which are currently approved for Soliris: the treatment of PNH to reduce hemolysis and the treatment of patients with atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy.12
As it is interchangeable, this biosimilar eculizumab is highly similar with no meaningful differences to reference eculizumab.12 A phase 3, randomized, double-blind, multi-national clinical trial comparing biosimilar eculizumab to reference eculizumab in patients with PNH established efficacy and safety.13 Frequently reported adverse reactions in the trial were headache, nasopharyngitis, back pain and nausea. Adverse events were reported in 72% of participants treated with biosimilar eculizumab and 68% of participants treated with reference eculizumab.12, 13
The FDA approved crovalimab-akkz (Piasky, Roche) for the treatment of adult and pediatric patients age 13 years or older with PNH and a body weight of at least 40 kg in June 2024.14 Crovalimab is a novel anti-C5 recycling monoclonal antibody. Approval was based on data from the phase 3 COMMODORE 3 trial.14
In the trial, patients were randomized to receive either crovalimab or eculizumabm and treatment in each arm lasted for 24 weeks. Patients could then continue treatment or switch to crovalimab for an extension period.15 Results from COMMODORE 2 showed that the rate of hemolysis control from week five to week 25 achieved was 79.3% among those treated with crovalimab compared to 79% for those given eculizumab.15 Of those in the crovalimab arm, 65.7% avoided red blood cell transfusions from baseline to week 25 compared to 68.1% for those in the eculizumab arm.15
Breakthrough hemolysis rates were 10.4% and 14.5% in the crovalimab and eculizumab arms, respectively. The proportions of patients with stabilized hemoglobin were 63.4% and 60.9% for crovalimab and eculizumab, respectively.15
A December 2023 Institute for Clinical and Economic Review (ICER) Report rated evidence for iptacopan versus continuing a C5 inhibitor as promising for moderate to substantial net benefit,
but inconclusive due to uncertainty about long-term benefit and safety, particularly related to breakthrough hemolysis and thrombosis.16 The panel recognized the more convenient oral formulation; however, due to a lack of evidence comparing efficacy between iptacopan and pegcetacoplan, the evidence was deemed insufficient.16
Notably, ICER issued this report prior to the release of additional data from the APPLY-PNH trial.16 For add-on danicopan to a C5 inhibitor for treatment-experienced PNH patients with clinically significant EVH, ICER rated danicopan as comparable or better than continuing a C5 inhibitor alone.16 There was a lack of comparative efficacy data; thus, the evidence of add-on danicopan versus pegcetacoplan was insufficient.16
The report noted that at a placeholder price of $485,000, iptacopan would be cost-saving compared to ravulizumab.16 Iptacopan currently has a wholesale acquisition cost of $542,560 annually. At a placeholder price of $150,000, treatment with addon danicopan was found to result in substantially higher costs.16
When it was first approved, eculizumab was known as the most expensive drug in the world for nearly 10 years; it is still one of the most expensive drugs for PNH, despite other available treatments.17 Because treatments for PNH are typically lifelong with costs that accumulate year after year, management in this category is increasingly critical.17 PNH’s total cost of care exceeds $1 million USD per patient per year.17 The entrance of biosimilars in the PNH category has the potential to impact the economic burden.
An expanding treatment landscape, including biosimilars, will require strategic payer management to achieve positive outcomes and mitigate costs.
An expanding treatment landscape, including biosimilars, will require strategic payer management to achieve positive outcomes and mitigate costs. A 2021 study conducted by Prime outlined opportunities for payers in PNH management that may result in better health care outcomes.18 Claims data assessed in the study showed four of 10 members treated with eculizumab had received higher than label dosing, four in 10 members had discontinued therapy and one in five had four or more transfusions during the study period.18 The study findings emphasized the need for management in this area as well as real-world cost assessments as more treatment options become available.18
Optimizing PNH drug therapy is critical. This may begin with prior authorization review to ensure the prescribed therapy is appropriate for the individual patient. Pharmacy benefit managers, including Prime, can provide ongoing PNH drug therapy via pharmacists who are PNH specialists.19 A particular integration of medical and pharmacy data and knowledge is key to establishing productive communication with providers about optimizing PNH drug therapy.19
References
1. Paroxysmal Nocturnal Hemoglobinuria. (2023, Jan. 5). National Organization for Rare Disorders. https://rarediseases.org/rarediseases/paroxysmal-nocturnal-hemoglobinuria/
2. PNH - Paroxysmal Nocturnal Hemoglobinuria. (2023). The Aplastic Anemia and MDS International Foundation. https://www.aamds.org/ diseases/pnh
3. Paroxysmal Nocturnal Hemoglobinuria (PNH). Johns Hopkins Medicine. Retrieved April 2, 2024, from https://www. hopkinsmedicine.org/kimmel-cancer-center/cancers-wetreat/blood-bone-marrow-cancers/paroxysmal-nocturnalhemoglobinuria-pnh
4. FDA approves new treatment for adults with serious rare blood disease. (2021, May 18). U.S. Food and Drug Administration. https:// www.fda.gov/drugs/news-events-human-drugs/fda-approves-newtreatment-adults-serious-rare-blood-disease
5. Ryan, C. (2023, Oct. 2). FDA Approves On-Body Injector for Self Administration of Pegcetacoplan for PNH. OncLive. https:// www.onclive.com/view/fda-approves-on-body-injector-for-selfadministration-of-pegcetacoplan-for-pnh
6. Brooks, A. (2023, Dec. 6). FDA Approves Iptacopan (Fabhalta) for Paroxysmal Nocturnal Hemoglobinuria. HCPLive. https:// www.hcplive.com/view/fda-approves-iptacopan-fabhalta-forparoxysmal-nocturnal-hemoglobinuria
7. Clinicaltrials.gov. (2023). Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment (APPLY-PNH). https://clinicaltrials.gov/ study/NCT04558918
8. Clinicaltrials.gov. (2023). Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy (APPOINT-PNH). https://clinicaltrials. gov/study/NCT04820530
9. Conroy, R. (2023, Dec. 11). Final APPLY-PNH Data Support Use of Iptacopan in PNH with Persistent Anemia. OncLive. https://www. onclive.com/view/final-apply-pnh-data-support-use-of-iptacopanin-pnh-with-persistent-anemia
10. Voydeya approved in the US as an add-on therapy to ravulizumab or eculizumab for treatment of extravascular haemolysis in adults with the rare disease PNH. (2024, April 1). AstraZeneca. https://www. astrazeneca.com/media-centre/press-releases/2024/voydeyaapproved-in-us.html
11. Long-Term ALPHA Phase III trial data showed danicopan as add-on to Ultomiris or Soliris sustained clinical improvements in subset of patients with PNH experiencing clinically significant extravascular haemolysis. (2023, Dec. 11). AstraZeneca. https://www.astrazeneca. com/media-centre/press-releases/2023/long-term-alpha-phase-iiitrial-data-danicopan-ultomiris-soliris-improvement-patients-pnhexperiencing-clinically-significant-extravascular-haemolysis.html
12. FDA Approves First Interchangeable Biosimilar for Two Rare Diseases. (2024, May 28). U.S. Food and Drug Administration. https://www. fda.gov/news-events/press-announcements/fda-approves-firstinterchangeable-biosimilar-two-rare-diseases
13. Jang, J.H., et al. (2023). A phase III, randomised, double-blind, multi-national clinical trial comparing SB12 (proposed eculizumab biosimilar) and reference eculizumab in patients with paroxysmal nocturnal haemoglobinuria. EJHaem. DOI: 10.1002/jha2.632
14. Ryan, C. (2024). FDA Approves Crovalimab for Paroxysmal Nocturnal Hemoglobinuria. OncLive, https://www.onclive.com/view/fdaapproves-crovalimab-for-paroxysmal-nocturnal-hemoglobinuria
15. Roth, A., et al. (2023). The Phase III, Randomized COMMODORE 2 Trial: Results From a Multicenter Study of Crovalimab vs. Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients Naïve to Complement Inhibitors. https://medically.roche.com/content/dam/pdmahub/ restricted/haematology/eha-2023/EHA-2023-presentation-roththe-phase-III-randomized-commodore-2-trial.pdf
16. Iptacopan and Danicopan for Paroxysmal Nocturnal Hemoglobinuria: Draft Evidence Report. (2023, Dec. 5). Institute for Clinical and Economic Review. https://icer.org/wp-content/uploads/2023/07/ PNH_Draft-Report_For-Publication_12052023.pdf
17. Peterson, J. (2021, Dec. 17). High Cost, Lifelong Treatments, and the Impact on Payers and Patients. RemedyOne. https://remedy-one. com/high-cost-lifelong-treatments-and-the-impact-on-payers-andpatients/
18. Burke, J.P., et al. (2021, Oct. 20). Paroxysmal Nocturnal Hemoglobinuria Real-World Effectiveness of C5 Inhibitors and Cost Assessment. Academy of Managed Care Pharmacy Nexus Meeting. https://www.primetherapeutics.com/wp-content/ uploads/2021/10/4085-B_PNH-C5-Assessment-1.pdf
19. Study: Opportunities to Improve Management of PNH Exist. (2022, Jan. 6). AIS Health. https://www.mmitnetwork.com/aishealth/ spotlight-on-market-access/study-opportunities-to-improvemanagement-of-pnh-exist/
Tiffanie Mrakovick, Pharm.D. Director of Pharmacy SummaCare
Pulmonary arterial hypertension (PAH) is a rare, progressive disorder characterized by high blood pressure, or hypertension, in the arteries of the lungs, or pulmonary arteries.1 Pulmonary arteries carry blood from the right side of the heart through the lungs.1 PAH most commonly affects women between the ages of 30 and 60.1 The cause of the disorder is unknown.1
About 15% to 20% of patients with PAH have inherited forms of PAH; they either have an autosomal dominant genetic condition associated with mutations in the BMPR2 gene or other recently identified genes or are members of a family in which PAH is known to occur as primary disease.1 PAH is also a secondary condition associated with other diseases, such as liver disease, congenital heart disease and connective tissue diseases like scleroderma or systemic sclerosis.1 More than 50% of PAH cases worldwide have no known cause.2
The World Health Organization (WHO) has defined five groups of patients with pulmonary hypertension (Table 2).3 Group 1, which consists of individuals with PAH, has a median survival time of more than five years after diagnosis.3 However, people with idiopathic PAH and connective tissue disease may have a shorter survival time.3 The mortality rates of the other groups vary.3
Symptoms of PAH include shortness of breath, especially during exercise, as well as chest pain and fainting episodes.1 People with PAH may also have a cough, sometimes with blood; an enlarged heart and liver; low blood pressure; and hoarseness due to compression of a nerve in the chest by an enlarged pulmonary artery.1 Puffiness or swelling of the face, ankles, abdomen and feet may occur in some affected individuals due to abnormal accumulation of fluid.1 As PAH advances, individuals may experience a bluish skin discoloration.1 In severe PAH cases, the right ventricle of the heart is abnormally enlarged, resulting in diminished function and potential heart failure.1 The WHO has defined functional assessment classifications for pulmonary hypertension and PAH that speak to disease and system severity, as well as impact of daily activities (Table 3).
Due to mild, nonspecific or infrequent symptoms, individuals with PAH may go years without proper diagnosis.1 Without proper treatment and management, hypertension in the lungs can cause the right heart to become overworked and weaken or fail over time.1 PAH is diagnosed through a combination of medical history, physical exam and diagnostic tests, which often include cardiac catheterization, blood tests, heart and lung imaging tests and electrocardiogram.2
There is typically no cure for PAH – the goal of treatment is to manage symptoms and slow disease progression.2 Drug treatments for PAH may include anticoagulation or blood thinners, digitalis or digoxin, or vasodilator therapy to relax blood vessels and lower blood pressure in the pulmonary artery. This therapy includes calcium channel blockers as well as a newer group of therapies called endothelin receptor antagonists (ERAs) and phosphodiesterase type 5 inhibitors (PDE5i).2 Treatment options also include prostacyclin analogues, prostacyclin receptor agonists and soluble guanylate cyclase stimulators (sGC).4
Sotatercept (Winrevair®)
In March 2024, the FDA approved sotatercept (Winrevair, Merck) for the treatment of PAH (WHO Group 1).5 The FDA granted sotatercept breakthrough therapy and orphan drug designations for the 45 mg and 60 mg doses.5 Sotatercept is a first-in-class activin signaling inhibitor that has been found to increase exercise capacity, improve WHO functional class and reduce the
risk of clinical worsening events in patients with PAH when added to background standard-of-care therapy.5
Approval was based on results from a multicenter, double-blind, phase 3 STELLAR trial of adult patients with PAH who were receiving stable background therapy.6 A total of 323 participants were randomized 1:1 to receive subcutaneous sotatercept or placebo every three weeks.6 The primary endpoint was change from baseline at week 24 in the 6-minute walk distance (6MWD). Secondary endpoints included multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro-B type natriuretic peptide level, improvement in WHO functional class, time to death or clinical worsening, French risk score and changes in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Physical Impacts, Cardiopulmonary Symptoms and Cognitive/Emotional Impacts domain scores.6
In the sotatercept group, the median change from baseline at week 24 in the 6MWD was 34.4 m compared to 1 m in the placebo group.6 The Hodges-Lehmann estimate of the difference in change from baseline at week 24 in 6MWD between the sotatercept and placebo groups was 40.8 m.6 All secondary endpoints were significantly improved with sotatercept as compared with placebo, except PAH-SYMPACT Cognitive/Emotional Impacts.6
Group Description
Class I
Class II
Class III
Class IV
PH = pulmonary hypertension
Patients with PH but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope.
Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope.
Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain or near syncope.
Patients with PH with inability to carry out any physical activity without limitations. These patients manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.
Drug Manufacturer Route of administration Mechanism of action Status
Ralinepag (APD811)
agonist Phase 3
Treprostinil (L606) Pharmosa Biopharm Inhaled Prostaglandin vasodilator Phase 3
Treprostinil palmitil (INS1009) Insmed Inhaled Prostaglandin vasodilator Phase 3
MK-5475 Merck Inhaled sGC stimulator Phase 3
Imatinib (AV-101) Aerovate Therapeutics Inhaled Tyrosine kinase inhibitor Phase 3
Seralutinib (GB002) Gossamer Bio; Pulmokine Inhaled Tyrosine kinase inhibitor; targeting PDGFR, CSF-1 and c-KIT Phase 3
Aurora-GT United Therapeutics; Northern Therapeutics IV Gene therapy Phase 2
Abbreviations: c-KIT = stem cell growth factor receptor kit; CSF1R = colony-stimulating factor 1 receptor; ERA = endothelin receptor antagonist; IV = intravenous; PDGFR = platelet-derived growth factor receptor; SC = subcutaneous; sGC = soluble guanylate cyclase *FDA granted tentative approval 11/4/2021; however, FDA final approval or launch has not occurred due to ongoing patent litigation.
Epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia and increased blood pressure were all adverse events associated with sotatercept.5 Health care providers should monitor hemoglobin and platelets for potential adverse effects before each of the first five doses of sotatercept.5
Researchers continue to investigate the still-uncertain efficacy of this treatment in patients with connective tissue disease and other comorbidities. Evaluation of efficacy of sotatercept in newly diagnosed intermediate- and high-risk PAH is being studied in a follow-up phase 3 trial over 6.5 years.7 Sotatercept is currently being investigated for treatment of combined postcapillary and precapillary PH due to heart failure with preserved ejection fraction in children with PAH and for the management of anemia in hematologic diseases.7
The FDA approved macitentan/tadalafil (OPSYNVI, Johnson & Johnson) single-table combination therapy for PAH (WHO Group 1) in March 2024.8 The combination therapy is specifically indicated for adult patients with PAH WHO Group I and WHO functional class (FC) II-III.8 Macitentan and tadalafil may be used in patients
with PAH who are treatment-naïve or who are already on an ERA, a PDE5i or both.8 It may be employed in patients who are currently treated concomitantly with stable doses of macitentan 10 mg and tadalafil 40 mg as separate tablets.8
Results from the multicenter, double-blind, adaptive phase 3 A DUE study informed approval.9 The trial included PAH patients, including treatment-naïve and prior ERA or PDE5i monotherapytreated patients.9 A total of 187 patients were randomized depending on their PAH treatment at baseline to receive singletablet macitentan/tadalafil, macitentan or tadalafil.9 Overall, the primary endpoint, pulmonary vascular resistance (PVR) reduction, was significantly greater with macitentan/tadalafil compared to macitentan or tadalafil on their own.8 Unrelated to treatment, three patients died in the macitentan/tadalafil arm.9 Patients transitioned to the open-label treatment period for 24 months following the treatment period.
A 2024 Institute for Clinical and Economic Review (ICER) report on treatment for PAH assessed the comparative clinical effectiveness and value of sotatercept.10 All panelists of the independent
appraisal committee found adequate current evidence to demonstrate a net health benefit for sotatercept compared to background therapy alone.10 The report noted a calculated healthbenefit price benchmark (HBPB) of between $17,900 to $35,400 per year for sotatercept.10
A major challenge in the PAH space is identifying at-risk patients and providing timely PAH diagnoses. Further, PAH is complex and requires higher level of care from specialists at care centers.11 Access to effective care may be a barrier for certain populations, so it is critical for payers to consider social determinants of health to ensure proper treatment and management.11 In the past several years, payers have prioritized social determinants of health when optimizing overall health outcomes with solutions such as transportation assistance, in-home support services in the home for older adult members and app-based medication delivery, particularly after hospital discharge.11
With new approvals in this space, payers will need to prioritize identification of patient populations and strategize how to ensure access while mitigating costs. The newly approved sotatercept shows improved clinical outcomes, but may exceed some cost-effectiveness thresholds.12 The Midwest Comparative
With new approvals in this space, payers will need to prioritize identification of patient populations and strategize how to ensure access while mitigating costs.
Effectiveness Public Advisory Council (CEPAC) policy roundtable recently convened to discuss different elements related to sotatercept and PAH, including delivery of the drug.12 Participants discussed the fact that pharmacies will play a key role in patient awareness and education, ensuring patients and clinicians receive the necessary information and support for home drug administration.12 Payers may opt to limit the drug to those in specific WHO PAH classes and those being treated with double or triple therapy, with an additional limit on age, considering the lack of trials investigating the drug in children.12 Ultimately, payer strategy will depend on pricing information.12
References
1. Pulmonary Arterial Hypertension. (2021, March 2). National Organization for Rare Disorders. https://rarediseases.org/rarediseases/pulmonary-arterial-hypertension/
2. What is Pulmonary Hypertension? (2021, May 1). National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health/ pulmonary-hypertension
3. Outlook and Life Expectancy for People with Pulmonary Hypertension (PH). (2023, Feb. 3). Healthline. https://www. healthline.com/health/pulmonary-hypertension-prognosis
4. Lau, E.M.T., et al. (2017). Epidemiology and Treatment of Pulmonary Arterial Hypertension. Nature Reviews Cardiology. https://www. nature.com/articles/nrcardio.2017.84
5. Bonavitacola, J. (2024, March 26). FDA Approves Sotatercept, First-in-Class Treatment for Adults with PAH. American Journal of Managed Care. https://www.ajmc.com/view/fda-approvessotatercept-first-in-class-treatment-for-adults-with-pah
6. Hoeper, M.M., et al. (2023). Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. New England Journal of Medicine, 388(16) 1478–1490. DOI: 10.1056/NEJMoa2213558
7. High-Cost Therapy Profile: Detailed Information about Sotatercept Subcutaneous (SC). (2024, March 14). Prime Therapeutics. https:// www.primetherapeutics.com/news/high-cost-therapy-profile-4/
8. U.S. FDA Approves OPSYNVI® (macitentan and tadalafil) as the First and Only Once-Daily Single-Tablet Combination Therapy for Patients with Pulmonary Arterial Hypertension. (2024, March 22). Johnson & Johnson. https://www.investor.jnj.com/news/
news-details/2024/U.S.-FDA-Approves-OPSYNVI-macitentanand-tadalafil-as-the-First-and-Only-Once-Daily-Single-TabletCombination-Therapy-for-Patients-with-Pulmonary-ArterialHypertension-PAH-2024-FqFYN-hx5S/default.aspx
9. Grunig, E., et al. (2024). Randomized Trial of Macitentan/Tadalafil Single-Tablet Combination Therapy for Pulmonary Arterial Hypertension. Journal of the American College of Cardiology, 83(4), 473–484. DOI: 10.1016/j.jacc.2023.10.045
10. ICER Publishes Final Evidence Report on Treatment for Pulmonary Arterial Hypertension. (2024, Jan. 8). Institute for Clinical and Economic Review. https://icer.org/news-insights/press-releases/ icer-publishes-final-evidence-report-on-treatment-for-pulmonaryarterial-hypertension/
11. Payer Considerations in the Management of Pulmonary Arterial Hypertension. (2023, May 4). American Journal of Managed Care https://www.ajmc.com/view/payer-considerations-managementpulmonary-arterial-hypertension-derek-van-amerongen
12. Hornick, I. (2023, Dec. 5). Report: Sotatercept improves clinical outcomes in PAH, but unlikely to be cost-effective. Healio https://www.healio.com/news/pulmonology/20231205/reportsotatercept-improves-clinical-outcomes-in-pah-but-unlikely-to-becosteffective
Gene Terkoski, Pharm.D., MBA Director, Pharmacy Care and Services
Health First Health Plans
Nonalcoholic steatohepatitis (NASH), or metabolic dysfunction associated steatohepatitis (MASH), is a more serious form of nonalcoholic fatty liver disease (NAFLD), or metabolic dysfunction-associated steatotic liver disease (MASLD), a condition in which fat builds up in the liver.1 Patients with NASH also experience inflammation and liver damage.1 The biggest risk factor for NASH is being overweight or obese. Other risk factors include diabetes, high cholesterol, high triglycerides, poor diet, metabolic syndrome, polycystic ovary syndrome, sleep apnea and hypothyroidism.1
NASH does not often manifest in outward signs or symptoms; however, those with NASH may experience fatigue or typically mild pain in the upper right abdomen.1 NASH can progress and lead to cirrhosis of the liver, which causes symptoms such as bleeding or bruising easily, itchy skin, jaundice, fluid accumulation in the abdomen, loss of appetite, nausea, swelling in the legs, confusion, drowsiness, slurred speech or spider-like blood vessels on the skin.1
Providers diagnose NASH through examination of medical history, a physical exam and tests to diagnose NAFLD, including differentiating between NASH and nonalcoholic fatty liver (NAFL).2 Providers may perform blood tests for elevated levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as routine imaging tests to detect fat in the liver.2 Imaging tests including ultrasound, CT scans or MRIs may assist in diagnosis.2 Elastography, a newer type of imaging test, can help determine advanced liver fibrosis and may be utilized to measure liver stiffness.2 Providers may perform elastography via vibration-controlled transient elastography, sheer wave elastography or magnetic resonance elastography.2 The only test that can prove a NASH diagnosis is a liver biopsy, which can detect fibrosis at earlier stages than elastography and clearly demonstrates the severity of disease.2
The approval of resmetirom is the first in the NASH space.
A predictive model forecasted that NASH cases will increase by about 83% from 11.61 million to 19.53 million in 2020 to 2039, respectively.3 This increase would result in projected cumulative direct health care costs of $1208.47 billion for obese NASH and $453.88 billion for non-obese NASH; projected NASH health care costs per patient would increase from $3636 to $6968.3 NASH is associated with a significant burden in the U.S.4 A recent realworld study showed a NASH population reported significantly lower mental and physical status, higher rates of anxiety and depression and increased health care resource utilization.4 Notably, the NASH population reported more health care provider visits, emergency department visits and hospitalizations.4
Treatment goals for NASH include managing conditions that increase risk for NASH or worsen the condition. Providers recommend lifestyle modifications such as reducing total
cholesterol level, maintaining a healthy weight, controlling diabetes, reducing alcohol intake and exercising regularly.5 Prior to 2024, there were no U.S. Food and Drug Administration (FDA)approved therapies for NAFLD and NASH.
In March 2024, the FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) as the first treatment for NASH, indicated for adults with NASH with moderate to advanced liver scarring, or fibrosis, to be used along with diet and exercise.6 Resmetirom is a thyroid hormone receptor-beta agonist that reduces the accumulation of fat in the liver.6
The approval of resmetirom is the first in the NASH space.6 Approval was based on safety and efficacy evaluated based on analysis of a surrogate endpoint at month 12 in a 54-month, randomized, double-blind, placebo-controlled trial.6 The trial included 888 adult patients who completed a liver biopsy showing inflammation due to NASH with moderate or advanced liver scarring. Participants were randomized to receive placebo, 80 mg resmetirom or 100 mg resmetirom once daily in addition to standard care for NASH.6, 7 A greater proportion of patients treated
Discover the latest insights from our leading oncology expert
Simone Ndujiuba, Pharm.D., BCOP Director, Clinical Strategy and Innovation, Oncology
Drug Manufacturer
Semaglutide (Wegovy®)
Azemiglitazone (MSDC-0602K)
Belapectin (GR-MD-02)
Efruxifermin (AKR-001)
Survodutide (BI 456906)
Pegozafermin (BIO89-100)
Tirzepatide (Zepbound™)
Clesacostat; ervogastat (PF-07055341)
Firsocostat (GS-0976)
Semaglutide + cilofexor; firsocostat Gilead Sciences; Novo Nordisk
Cenicriviroc; tropifexor (LJC242)
Cilofexor (GS-9674) Gilead Sciences
Tropifexor (LJN452)
Ervogastat (PF-06865571)
Naltrexone (JKB-122)
Denifanstat (TVB-2640)
Rencofilstat (CRV431)
Abbreviations: ACC = Acetyl-CoA carboxylase; DGAT2 = diacylglycerol O-acyltransferase 2; FASN = fatty acid synthase; FXR = farnesoid X receptor;
= glucagon-like peptide-1; IV = intravenous; PPAR = peroxisome proliferator-activated receptor; SC = subcutaneous; SCD-1 = stearoyl-CoA desaturase 1; SGLT1 = sodium glucose cotransporters 1; SGLT2 = sodium glucose cotransporters 2; siRNA = small interfering RNA; THR-β = thyroid hormone beta receptor; TLR4 = toll-like receptor 4
with resmetirom achieved NASH resolution or an improvement in liver scarring at 12 months compared with those who received placebo, based on liver biopsy results.7
Of those who received 80 mg and 100 mg resmetirom, 26% to 27% and 24% to 36% of subjects experienced NASH resolution with no worsening of liver scarring, respectively, compared to 9% to 13% of those who received placebo.7 Further, 23% of those who received 80 mg resmetirom and 24% to 28% of those who received 100 mg of resmetirom experienced an improvement in liver scarring and no worsening of NASH, compared to 13% to 15% of those who received placebo.7 Different pathologists’ readings are reflected in the range of responses.7
Side effects associated with resmetirom include diarrhea and nausea.6, 7 Additionally, warnings and precautions include druginduced liver toxicity and gallbladder-related side effects.6 There is a third warning in the label for interaction with certain statins, which is significant, since high cholesterol is a common comorbidity in the patient population. Utilization should be discontinued if patients develop signs and symptoms of worsening liver function while on resmetirom.6 Treatment should be avoided in patients with decompensated cirrhosis.6
Per FDA approval, Madrigal Pharmaceuticals is required to conduct a post-approval study to verify and describe clinical benefit.6 This
will be completed through the ongoing 54-month study.6
An Institute for Clinical and Economic Review (ICER) report from May 2023 noted a majority of panelists found evidence is adequate to demonstrate a net health benefit for resmetirom compared to lifestyle management alone.8 ICER calculated that resmetiron’s health-benefit price benchmark (HBPB) is between $39,600 to $50,100 per year.8 The annual wholesale acquisition cost (WAC) for resmetirom is $47,400, to be made available through a limited network of specialty pharmacies.
Now that the FDA has made its first approval in the NASH space, payers will prioritize strategic management of a brand-new expense category. Since resmetirom approval has been limited to patients with moderate to severe scarring, managing access to those who will benefit may be an important strategy. Structuring access around other lifestyle modifications standard to NASH care may also be critical to achieving optimal outcomes. Potential strategies to consider may include prior authorization requirements to confirm diagnosis, promotion of adherence to labeled drug indications and ensuring specialist consultation. Utilization management may be an important method of ensuring access to the appropriate patient population to optimize outcomes and manage costs.
References
1. Non-alcoholic steatohepatitis (NASH). (2022). Cedars Sinai. https:// www.cedars-sinai.org/health-library/diseases-and-conditions/n/ non-alcoholic-steatohepatitis-nash.html
2. Diagnosis of NAFLD & NASH. (2021, April). National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk. nih.gov/health-information/liver-disease/nafld-nash/diagnosis
3. Younossi, Z.M., et al. (2022). The Growing Economic and Clinical Burden of Nonalcoholic Steatohepatitis (NASH) in the United States. Journal of Clinical and Experimental Hematology, 13(3), 454–467. DOI: 10.1016/j.jceh.2022.12.005
4. Tapper, E.B., et al. (2023). The burden of nonalcoholic steatohepatitis (NASH) in the United States. BMC Gastroenterology, 23(109). DOI: 10.1186/s12876-023-02726-2
5. Treatment for NASH. Stanford Medicine. Retrieved April 12, 2024, from https://stanfordhealthcare.org/medical-conditions/liver-kidneys-andurinary-system/nonalcoholic-steatohepatitis-nash/treatments.html
6. FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease. (2024, March 14). U.S. Food and Drug Administration. https://www.fda.gov/news-events/pressannouncements/fda-approves-first-treatment-patients-liverscarring-due-fatty-liver-disease
7. Harrison, S.A., et al. (2024). A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. The New England Journal of Medicine, 390(6), 497–509. DOI: 10.1056/NEJMoa2309000
8. ICER Publishes Final Evidence Report on Treatments for Non-Alcoholic Steatohepatitis. (2023, May 25). Institute for Clinical and Economic Review. https://icer.org/news-insights/press-releases/icerpublishes-final-evidence-report-on-treatments-for-non-alcoholicsteatohepatitis/
Timothy O’Shea, Pharm.D. Director, Specialty Pharmacy
Kavita Parmar, Pharm.D. Manager, Clinical Pharmacy Operations
Multiple sclerosis (MS) is a central nervous system (CNS) disease that affects nearly 1 million people in the U.S.1 Often considered an autoimmune disease, the condition disrupts the communication between the brain and the rest of the body. Initial onset of MS often occurs between the ages of 20 and 40.2
There are four disease courses in MS: clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS) and secondary progressive MS (SPMS).2 RRMS is the most common disease course and is characterized by clearly defined attacks of new or increasing neurologic symptoms. In RRMS, attacks or relapses are followed by periods of partial or complete recovery, or remissions.2 An estimated 85% of MS patients are initially diagnosed with RRMS. SPMS is secondary to an initial diagnosis of RRMS; some patients with RRMS eventually transition to SPMS, which occurs with progressive worsening of neurologic function over time.2 A minority of MS patients are diagnosed with PPMS, which is characterized by worsening neurologic function from the onset of symptoms, without relapses or remissions.2
The first symptom of MS is commonly blurred or double vision, red-green color distortion or even blindness in one eye. Most MS patients experience muscle weakness and difficulty with coordination, and these symptoms can be severe enough to impair walking or standing.3 Other common symptoms of MS are paresthesia, transitory abnormal sensory feelings such as numbness, prickling or “pins and needles” sensations; pain; speech impediments; tremors; bladder dysfunction; bowel dysfunction; sexual problems; and dizziness. Around 50% of MS patients suffer from cognitive impairments such as difficulty with concentration, attention, memory or poor judgment. In severe cases, patients with MS can develop partial or complete paralysis.3
Proper diagnosis of MS often entails a comprehensive process that may include medical history, neurologic exam, MRI, spinal fluid analysis and blood tests to rule out conditions with overlapping symptoms.3 The criteria for an MS diagnosis include: evidence of damage in at least two separate areas of the CNS, including the brain, spinal cord and optic nerves; evidence that damage occurred at different points in time; and no other possible diagnosis.4 The Revised McDonald Criteria from the International Panel on the Diagnosis of MS has specific guidelines for using MRI and cerebrospinal fluid analysis in the diagnostic process for MRI; according to these guidelines, MRI can be used to look for a second area of damage in a person who has experienced only one attack (or a relapse or exacerbation) of MS-like symptoms and can also be used to confirm that damage has occurred at two different points in time.5
Although there is no cure for MS, there are more than 20 medications approved by the U.S. Food and Drug Administration (FDA) to slow the progression of disability and reduce the risk of relapse. These medications are available in injectable, oral and infusion form. Practice Guidelines from the American Academy of Neurology (AAN) state that when a disease-modifying therapy (DMT) is being considered, clinicians should incorporate and review preferences in terms of safety, route of administration, lifestyle, cost, efficacy, common adverse effects and tolerability in the choice of DMT.6
In August 2023, the FDA approved the first biosimilar to treat MS, natalizumab-sztn (Sandoz).7 This is the first biosimilar to the natalizumab (Tysabri®) injection for the treatment of adults with relapsing forms of MS.7 Natalizumab-sztn is approved to treat the following relapsing forms of MS: CIS, RRMS and active SPMS.
Approval was based on data from the phase 3 Antelope study of 264 adults with RRMS in 48 centers in seven different countries randomized to receive either the reference or biosimilar natalizumab.8 The primary end point was cumulative number of new active lesions on MRI by 24 weeks, with secondary end points including annualized relapse rate (ARR) and change from baseline Expanded Disability Status Scale (EDSS) score after 24 and 28 weeks.8 Results showed
In August 2023, the U.S. Food and Drug Administration (FDA) approved the first biosimilar to treat MS, natalizumab-sztn (Tyruko).
no clinically relevant difference in the mean cumulative number of new active lesions between the two groups.8 The two groups had similar ARR at 24 and 48 weeks. Both groups had similar baseline EDSS score, and changes were minimal and similar for both groups.8
ocrelizumab (Ocrevus® SC) Roche; Halozyme SC
(GDC-0853) Genentech;
Tolebrutinib (SAR442168)
(LOU064)
Ocrelizumab (Ocrevus HD) Roche IV
Ocrelizumab (CT-P53) Celltrion Healthcare IV
Amantadine hydrochloride
Abbreviations:
= chimeric antigen receptor
Natalizumab products come with a boxed warning about the increased risk of progressive multifocal leukoencephalopathy (PML), a viral infection of the brain that usually leads to death or severe disability.7 Due to the risk of PML, natalizumab products are available through a restricted drug distribution program under a risk evaluation and mitigation strategy (REMS).7 Other warnings include risks regarding herpes infection, thrombocytopenia, immunosuppression and serious hypersensitivity reactions such as anaphylaxis and hepatotoxicity.7 Side effects associated with natalizumab are headache, fatigue, arthralgia, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea and rash.7
MS is an expensive category in terms of payer management. According to the Magellan Rx 2023 Medical Pharmacy Trend Report, MS was number three in the top 10 drug therapy categories by per member per month (PMPM) commercial spend and increased 13% from 2021 to 2022; it was also in the top 10 for Medicare and Medicaid.9 The second-highest drug for commercial PMPM spend for 2021-2022 was Ocrevus for MS.
Tysabri, the reference drug for the first MS biosimilar approval, ranked ninth in the top 25 drug PMPM spend for 2021–2022.9 This first biosimilar approval for an MS therapy may result in potential savings for payers.
A recent IQVIA analysis examined the impact of biosimilar savings in the U.S., showing that the use of biosimilars has saved more than $40 billion over the past five years, and that number is expected to rise to more than $180 billion in the next five years.10 The increased competition due to biosimilars often leads to cost savings. PBMs anticipate that biosimilars will impact the global burden of costs for MS management. In the U.S., biosimilars are less expensive than reference drugs by about 10% to 20%.11 Formulary access has a major impact on which product payers prefer.12 In some cases, prior authorization or criteria requiring new patients to initially utilize a biosimilar before potentially switching to a reference is one strategy driving biosimilar utilization and market share, and often savings.12 Collaboration between payers and health systems is another strategy that can drive biosimilar use through aligned formularies. Provider familiarity with biosimilars is critical to increasing access, and educational awareness is important to help key members, including nursing and infusion staff, comfortably address patient concerns and questions.11
References
1. MS Prevalence. National Multiple Sclerosis Society. Retrieved April 8, 2024, from https://www.nationalmssociety.org/About-theSociety/MS-Prevalence
2. Types of MS. National Multiple Sclerosis Society. Retrieved April 8, 2024, from https://www.nationalmssociety.org/What-is-MS/Typesof-MS
3. Multiple Sclerosis Information Page. National Institute of Neurological Disorders and Stroke. Retrieved April 8, 2024, from https://www.ninds.nih.gov/Disorders/All-Disorders/MultipleSclerosis-Information-Page
4. How MS is Diagnosed. National Multiple Sclerosis Society. Retrieved April 8, 2024, from https://www.nationalmssociety.org/SymptomsDiagnosis/Diagnosing-MS
5. Updated McDonald Criteria Expected to Speed the Diagnosis of MS and Reduce Misdiagnosis. (2017, Dec. 21). National Multiple Sclerosis Society. https://www.nationalmssociety.org/About-the-Society/ News/Updated-McDonald-Criteria-Expected-to-Speed-the-Di
6. Practice Guideline Recommendations: Disease-Modifying Therapies for Adults with Multiple Sclerosis. (2021, Sept. 18). American Academy of Neurology. https://www.aan.com/Guidelines/home/ GuidelineDetail/898.
7. FDA Approves First Biosimilar to Treat Multiple Sclerosis. (2023, Aug. 24). U.S. Food and Drug Administration. https://www.fda.gov/newsevents/press-announcements/fda-approves-first-biosimilar-treatmultiple-sclerosis
8. Hemmer, B., et al. (2023). Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients with Relapsing-Remitting Multiple Sclerosis. Journal of the American Medical Association Neurology, 80(3), 298–307. DOI: 10.1001/jamaneurol.2022.5007
9. 2023 Medical Pharmacy Trend Report. Magellan Rx Management. https://issuu.com/magellanrx/docs/medical-pharmacy-trendreport-2023?fr=sYmEzZTY2MjgzNzc
10. Biosimilars in the United States 2023-2027. (2023, Jan. 31). IQVIA Institute. https://www.iqvia.com/insights/the-iqvia-institute/ reports-and-publications/reports/biosimilars-in-the-unitedstates-2023-2027
11. Meglio, M. (2023, Nov. 27). Biosimilars Enter the Multiple Sclerosis Treatment Paradigm. NeurologyLive. https://www.neurologylive. com/view/biosimilars-enter-ms-treatment-paradigm
12. Payer Perspective: Incentives for Biosimilars and Formulary Access (2023, Sept. 20). Managed Healthcare Executive. https://www. managedhealthcareexecutive.com/view/payer-perspectiveincentives-for-biosimilars-and-formulary-access
David Lassen, Pharm.D. Chief Clinical Officer Prime Therapeutics
Around 42% of the U.S. population lives with obesity, increasing the demand for weight loss solutions.1 In recent years, the glucagon-like peptide-1 (GLP-1) receptor agonist class has proven to not only effectively manage type 2 diabetes (T2DM) but also effectively treat obesity.2, 3 These therapies may have the potential to meet a growing weight management need.
GLP-1, a hormone secreted after the ingestion of food, stimulates glucose-dependent insulin secretion, suppresses glucagon, delays gastric emptying and reduces energy intake.4 GLP-1 receptor agonists work to lower blood glucose levels through different mechanisms and have been found to have profound effects on visceral and ectopic fat.4
The U.S. Food and Drug Administration (FDA) first approved exenatide (Byetta®) in 2005 for the treatment of T2DM and since has approved several GLP-1 receptor agonists for the treatment of T2DM. In more recent years, GLP-1 receptor agonists have been approved for the treatment of obesity and weight loss, including liraglutide (Saxenda®) and semaglutide (Wegovy®).5 In 2019, the FDA approved the first oral GLP-1 treatment for T2DM, semaglutide (Rybelsus®).6 Liraglutide (Saxenda) was approved by the FDA in 2014 as the first GLP-1 treatment indicated for weight management.7 Table 7 outlines the current FDA-approved GLP-1 treatments, indications, dosing and wholesale acquisition cost (WAC).
In November 2023, the FDA approved tirzepatide (Zepbound, Lilly) injection indicated for chronic weight management in adults with obesity or who are overweight with at least one weight-related condition for use, in addition to a reduced calorie diet and increased physical activity.8 Specifically, tirzepatide is indicated as an adjunct therapy to a reduced calorie diet and increased physical activity in adults with a body mass index (BMI) of 30 kg/m2 or greater, or 27 kg/m2 or greater with at least one weight-related comorbidity. Some conditions considered weight-related in this indication include high blood pressure, T2DM or high cholesterol.8 Tirzepatide is a GLP-1 receptor agonist and a glucosedependent insulinotropic polypeptide (GIP).8
Results from two randomized, double-blind, placebo-controlled trials of adults with obesity or who were overweight with at least one weight-related condition established the effectiveness of tirzepatide.9, 10 These trials included 2,519 patients who received either 5 mg, 10 mg or 15 mg of tirzepatide once weekly as well as 958 patients who received once-weekly placebo injections.9, 10
Weight reduction was measured after 72 weeks.9, 10 Across both trials, patients who received tirzepatide at all three dose levels experienced statistically significant reduction in body weight (at least 5%) at 72 weeks compared to the placebo group.9, 10 One trial enrolled adults without diabetes. In this trial, participants who received the highest approved dosage of tirzepatide lost on average 18% of their body weight compared to who received placebo.9 The other trial included adults with T2DM, and those who received the highest dosage of tirzepatide lost, on average, 12% of their body weight compared to who received placebo.10
Side effects associated with tirzepatide include nausea, diarrhea, vomiting, constipation, abdominal discomfort and pain, injection site reactions, fatigue, hypersensitivity reactions, burping, hair loss and gastroesophageal reflux disease.8 It is important to note that tirzepatide has not been studied in patients with a history of pancreas inflammation or severe gastrointestinal disease.8 Tirzepatide should not be used in combination with Mounjaro® or any GLP-1 receptor agonist.8
According to a 2023 Kaiser Family Foundation survey, around 60% of adults who are trying to lose weight as well as a quarter of those not currently trying to lose weight would be interested in trying a weight-loss drug.11 The recent trend of increased utilization in the GLP-1 agonist class is expected to continue. Data shows the use of semaglutide (Ozempic®) is increasing 75% on
a rolling 12-month average.12 This represented an estimated $67 billion in spend.12 While Ozempic is indicated by the FDA for the treatment of T2DM, the increased utilization is tied to weight loss and treating obesity.12 The share of users with a T2DM diagnosis decreased by 16% from 2018 to 2021, while the share of users who were overweight without a diagnosis of T2DM increased by 225%.12 Per Morgan Stanley research estimates, the U.S. market for obesity drugs is projected to reach $51 billion by 2030.13
A Prime and Magellan Rx integrated pharmacy and medical claims data analysis assessed 16 million commercially insured members to identify those who started taking a GLP-1 between January 1, 2021 and December 31, 2021. The analysis found adherence to these drugs was poor, with just 27% adherent to GLP-1 therapy during the first year of treatment. There was also a substantial increase in health care costs in the first year, at $7,727 a person. The increase in cost was even higher among GLP-1 adherent individuals, at $13,218 higher total cost of care per person.
Recent industry utilization trends show a substantial increase in use of T2DM GLP-1 therapies for weight loss, so evidence-based approaches to management will be critical to addressing the soaring demand and their impact on total cost of care. Prime and Magellan Rx provides various strategies and services to address these concerns. Many of these strategies are critical to mitigating costs and achieving optimal outcomes.
(Saxenda)
(Wegovy)
Recent industry utilization trends show a substantial increase in use of T2DM GLP-1 therapies for weight loss, so evidence-based approaches to management will be critical to addressing the soaring demand and their impact on total cost of care.
Tracking enhanced utilization and trends for GLP-1s, inclusive of drug-specific forecasting, is one service Prime employs to effectively manage the category. Weight loss products, including select GLP-1s, may be offered as an optional benefit election. Utilization management can be applied to formulary drugs to limit the indications for which coverage is granted, and PBMs can employ enhanced utilization management strategies such as validation processes and use of integrated medical data. Specifically, diabetic GLP-1 prior authorization (PA) criteria may allow for coverage for diagnosis of T2DM and exclude coverage for weight loss; this would require validation of trial and failure of guideline-supported cost-effective prerequisite therapy in appropriate patients as well as validation of T2DM diagnosis with medical record documentation of ICD-10 diagnosis code. Integrated medical claims data may support the ability to capture
patient diagnosis with ICD-10 code at point of sale (POS) and bypass the need to submit a PA for preferred GLP-1 medications. This strategy would reduce member and provider abrasion in addition to administrative costs associated with the PA process while still ensuring clinically appropriate, on-label use. PA criteria for GLP-1s should ensure these agents are used safely and effectively according to clinical guidelines and in conjunction with increased physical therapy and behavioral modifications.
Prime and Magellan Rx’s Core and Advanced Fraud, Waste and Abuse (FWA) product provides active monitoring for GLP-1 medication fraud, waste and abuse through advanced analytics that leverage integrated medical and pharmacy data. Any pharmacy, member or prescriber behavior deemed potentially problematic is flagged and escalated for investigation or audit as appropriate. The service commonly finds misrepresented information on PA documents and lack of adequate diagnosis or tried and failed therapies.
Prime and Magellan Rx additionally offers a HighTouchRx product, which uses end-to-end data, paired with advanced clinical rules and machine learning, to identify non-optimized drug use. Specialized pharmacists perform provider outreach to recommend drug therapy optimization. Following pharmacist intervention, we generate a report to provide data on dollar savings. This program has successfully eliminated duplicative diabetic therapies and optimizes diabetic treatment regimens for members.
Prime is developing an integrated weight loss product and lifestyle program that will support sleep, nutrition, exercise, diabetes prevention, drug strategy, medication off-ramps and food-as-medicine concepts that will align benefit elections and low-net-cost formulary strategy.
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References
1. FastStats: Obesity and Overweight. Centers for Disease Control and Prevention. Retrieved August 17, 2023, from https://www.cdc.gov/ nchs/fastats/obesity-overweight.htm
2. Nauck, M.A., et al. (2020). GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art. Molecular Metabolism, 46, 101102. DOI: 10.1016/j.molmet.2020.101102
3. Jensterle, M., et al. (2022). Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review. Advanced Therapies, 39(6), 2452–2467. DOI: 10.1007/ s12325-022-02153-x
4. Senn, J., et al. (2023). Glucagon-Like Peptide-1 Agonist. Visceral and Ectopic Fat. https://www.sciencedirect.com/topics/medicine-anddentistry/glucagon-like-peptide-1-agonist
5. Amylin and Lilly Announce FDA Approval of BYETTA™ (Exenatide) Injection. (2005, 20 April). Lilly. https://investor.lilly.com/newsreleases/news-release-details/amylin-and-lilly-announce-fdaapproval-byettatm-exenatide
6. FDA approves first oral GLP-1 treatment for type 2 diabetes. (2021, Sept. 20). U.S. Food and Drug Administration. https://www.fda.gov/ news-events/press-announcements/fda-approves-first-oral-glp-1treatment-type-2-diabetes
7. FDA approves weight management drug for patients aged 12 and older. (2021, June 15). U.S. Food and Drug Administration. https:// www.fda.gov/drugs/news-events-human-drugs/fda-approvesweight-management-drug-patients-aged-12-and-older
8. FDA Approves New Medication for Chronic Weight Management (2023, Nov. 8). U.S. Food and Drug Administration. https://www. fda.gov/news-events/press-announcements/fda-approves-newmedication-chronic-weight-management
9. Jastreboff, A.M., et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. The New England Journal of Medicine, 387(3), 205–216. DOI: 10.1056/NEJMoa2206038
10. Frandsen, C.S. (2023). SURMOUNT-2: new advances for treating obese type 2 diabetes with tirzepatide. The Lancet, 402(10402), 586–588. DOI: 10.1016/S0140-6736(23)01292-8
11. Poll: Nearly Half of Adults Would Be Interested in Prescription WeightLoss Drugs, But Enthusiasm Fades Based on Lack of Coverage and Risk Regaining Weight. (2023, Aug. 4). Kaiser Family Foundation. https://www.kff.org/health-costs/press-release/poll-nearly-halfof-adults-would-be-interested-in-prescription-weight-loss-drugsbut-enthusiasm-fades-based-on-lack-of-coverage-and-risk-ofregaining-weight/
12. Beal, A. (2023, Oct 3). How to Maintain Appropriate GLP-1 Utilization Without Breaking the Bank. SelectHealth. https:// selecthealth.org/scripius/industry-insight/glp1-utilization
13. Obesity Drugs Boost Pharma’s Growth Outlook. (2023, Sept. 6). Morgan Stanley. https://www.morganstanley.com/ideas/obesitydrugs-investment-opportunity
Artificial intelligence (AI) can be applied by payers and pharmacy benefit managers (PBMs) in a variety of innovative ways. In the payer and PBM space, AI is currently being used to offset administrative tasks. For example, AI engines can comb through hubs of documents, contracts and amendments with unstructured language and find and summarize key terms, often shortening review time from hours or days to minutes. Models are trained to identify specific elements of contracts and documents to index them into easy-to-read tables and outputs, reducing the risk of human error and omissions. These can also be indexed to data such as contract start dates or types.
AI also brings opportunities to the health care space, including improved efficiency and cost savings, improved quality, data-driven decisions, innovation in care delivery and fraud detection and prevention.
AI can automate the review of vast pools of patient care records and financial transactions to ensure accuracy and compliance with policies and regulations. AI-driven auditing tools can identify inconsistencies or anomalies in billing and operations, reducing manual effort and time.
By applying AI to historical and real-time data, payers can forecast future trends in health care needs, costs and patient outcomes. Predictive analytics can inform strategic planning, resource allocation and risk management efforts. Some payers are exploring the use of AI models to predict patient health outcomes based on medication adherence patterns, genetic information and other health indicators that can come from prior authorization (PA) and claims data.
Fraud detection
Machine learning algorithms are being employed to analyze claims data to identify patterns that indicate fraud, waste and abuse (FWA),
ensuring resources are being used ethically and responsibly. Leveraging AI algorithms, managed care organizations can detect fraudulent activities by analyzing patterns and anomalies in billing and claims data. AI systems can continuously learn and adapt to new fraudulent schemes, offering real-time detection and prevention.
AI can analyze patient data, including health records and lifestyle information, to develop personalized care plans, ready for clinician review, that optimize treatment outcomes. Predictive models can forecast potential health issues and suggest preventive measures tailored to individual patient profiles.
AI tools offer real-time, evidence-based recommendations to health care providers by analyzing current patient data against vast medical knowledge bases. This support can improve diagnosis accuracy, suggest treatment options and highlight drug interactions or contraindications.
AI offers enhanced data security monitoring and analysis of network behavior, identifying potential threats and automating responses to suspicious activities. AI-driven monitoring and auditing of data handling practices can ensure compliance with health care regulations such as HIPAA.
AI-powered chatbots can provide patients 24/7 assistance, answering inquiries, offering health care navigation advice, escalating issues to personnel and guiding patients through insurance or treatment processes. These chatbots can reduce the workload on human staff, allowing them to focus on more complex tasks.
AI can optimize inventory levels and predict supply chain disruptions by analyzing usage patterns, lead times and external factors. Applying AI technology in this way ensures necessary
medical supplies are adequately stocked and can be replenished efficiently, avoiding shortages or excesses.
AI automates routine administrative tasks such as patient scheduling, claims processing and documentation, improving operational efficiency. Machine-learning algorithms can also optimize staffing levels and reduce administrative costs by identifying inefficiencies.
Prime Therapeutics and Magellan Rx‘s Enterprise Data and Information Governance Committee oversees policies and procedures related to all manifestations and applications of AI and generative AI at the organization. The committee evaluates applications of AI for risk, ensuring responsible, secure, private, ethical and compliant AI use. Ultimately, the committee applies the rules across enterprise personnel inclusive of employees, contractors, interns and beyond in order to manage AI’s use and impact.
Sean Wuest, Pharm.D. Clinical Program Account Manager
Magellan Rx Management
Mark Santilli, Pharm.D.
Sr. Director, Clinical Strategy and Programs
Magellan Rx Management
In 2008, the Centers for Medicare & Medicaid Services (CMS) launched the 5-Star Quality Rating System for Medicare Advantage Prescription Drug (MAPD) plans with a bidirectional goal of improving the quality of care delivered to Medicare beneficiaries and reducing overall health care expenditures. The 2024 Star Ratings, applicable to calendar year 2022, have 42 unique measures distributed across nine different domains on both the Part C and Part D benefit.
MAPD plans receive an annual Star Rating, which aggregates the plan’s performance in individual measures from 1 to 5, as well as categorical adjustments and reward factors. A health plan’s overall Star Rating has significant implications — arguably the most notable being that plans with an overall rating of 4 stars or higher are eligible for quality bonus payments (QBPs) from CMS that can be used to enhance benefit offerings for members. Additionally, top performing plans can receive a high performing plan icon, favorable placement on the Medicare Plan Finder and expanded enrollment options. Conversely, CMS reserves the right to terminate a consistently low-performing plan’s Medicare contract.
Since their inception, CMS Star Ratings have evolved with measure additions and removals, plus measure weighting changes that have substantial impacts on overall plan performance. A central challenge for plans is the uncertainty of Star cut points. Plans are also at a disadvantage given the benchmarks applicable for the calendar year are not released until the following October (e.g., calendar year 2024 benchmarks are released in October of 2025). The 2024 Star Ratings, applicable to measurement year (MY) 2022, include 12 unique Part D measures and account for 35% of a MAPD plan’s overall Star Rating.
In assessing national performance trends, Star Ratings pose a variety of challenges for MAPD plans as they strive to reach and maintain 4- and 5-Star performance. The publicly available national data for Star Ratings 2024 and 2023 (measurement year 2022 and 2021, respectively), demonstrate key learnings and focal points for plans to consider each year. In particular, the analysis focuses on Part D clinical measures that MAPD plans can directly impact year-over-year.
The most noteworthy change in the 2024 Star Ratings for diabetes adherence cut points was the 5-Star decline from 92% to 90%, which is historically uncommon. Despite a 2% decrease for the 5-Star Rating, more than one-third (37.5%) of plans that achieved 5 Stars in measurement year 2021 saw their diabetes adherence performance drop in measurement year 2022. A 1% decline in the 3-Star threshold from 85% to 84% allowed more than 75% of 3-Star plans to retain their 3-Star rating year over year. The 4-Star benchmark remained constant at 88% for measurement year 2022, yet 21% of MY2021 4-Star plans experienced a decrease in performance year-over-year. Average year-over-
year performance was most pronounced in plans that achieved 1 or 5 Stars in 2021; 1-Star plans have an average treatment rate improvement of 5.6%, while 5-Star plans lost 3.6% on average.
Average treatment rate changes, coupled with the percentage of plans that had Star Rating changes year to year, highlight the fact that lower-performing plans have the greatest capacity for upward improvement, while the highest-performing plans struggle to maintain their performance from the previous year. Plans with 2-, 3- and 4-Star performance had minimal changes to average treatment rate performance, but the overall distribution of 3-Star plans increased from 38.8% to 43.3% year-over-year. The 4-Star distribution dropped more than 7% to 22.9% of plans, while the percentage of 5-Star plans jumped from 3.6% to 13.7%.
The medication adherence for hypertension (RAS antagonists) cut points experienced minimal changes — only the 2-Star increased 4% from 78% to 82%. With no changes to the 3-, 4- and 5-Star benchmarks, the majority of plans retained the same Star Rating from measurement year 2021 to 2022. From 2021 to 2022, there were minimal (<1%) average treatment rate changes for 3-, 4- and 5-Star plans; plans that achieved only 1 Star in 2021 demonstrated outsize gains, improving 5.7% on average.
With no changes to the 3-, 4- and 5-Star benchmarks, there were no sizeable shifts in overall distribution among contracts.
A central challenge for plans is the uncertainty of Star cut points.
More than 20% of 2021 5-Star plans did not retain their 5-Star performance in calendar year 2022, which was likely due in part to an average performance decline of 0.8% year-over-year. This reinforces the challenges high performing plans face in order to improve and maintain their Star Rating year to year. We saw the highest trends in average year-over-year improvement among 1and 2- Star plans at +5.7% and +1.3%, respectively.
Medication adherence for cholesterol (statins) – MAPDs:
The medication adherence for cholesterol (statins) benchmarks experienced further tightening in calendar year 2024: the 5-Star benchmark dropped 1% to 91%, 4-Star remained unchanged at 88% and 3-Star increased from 85% to 86%. Plans that achieved 5 Stars in 2021 saw an average treatment rate decline of 1.7%, which likely influenced the 1% decrease in the 5-Star cut point. Again, more than 20% of 5-Star plans dropped from their prior Star rating from 2021 to 2022, but the overall distribution of 5-Star plans increased from 6.7% to 12.8%. Nearly one-third of 3-Star plans realized Star Rating improvements year over year. Statin adherence was the only adherence measure to see 3-Star
With benchmarks on the rise and substantial changes coming for the MTM identification criteria, plans should work to bolster their MTM offering and divert appropriate resources to maintain their Star performance.
distribution fall below 30%, dropping nearly 10% year-overyear to 21.7%. Nearly half (48.6%) of plans achieved 4 or 5 Stars nationally due to distribution changes from 2021 to 2022.
The Medication Therapy Management (MTM) Completion Rate for Comprehensive Medication Review (CMR) measure saw aggressive cut point increases across every Star benchmark. The
5-Star cut point rose to a record 92% high from 90%, while the 2- and 3-Star cut points increased 20% and 10%, respectively. As a result, nearly 60% of MAPDs that achieved a 5-Star Rating in 2021 experienced a Star Rating decrease in measurement year 2022; performance distribution dropped from 31.1% of plans achieving 5 Stars for measurement year 2021 to only 15.9% in 2022. Additionally, the average 5-Star performance declined by 2.8% from MY2021 to MY2022. The relative distribution for 1- and 2-Star plans remains relatively low at 6.9% and 7.3% of MAPDs, respectively, but both cohorts saw double-digit average improvements year-over-year. With benchmarks on the rise and substantial changes coming for the MTM identification criteria, plans should work to bolster their MTM offering and divert appropriate resources to maintain their Star performance.
The statin use in persons with diabetes (SUPD) measure also saw record-high benchmarks for MY2022 for every Star Rating (2, 3, 4 and 5) threshold. The cut point increase impacts were profound — more 50% of plans with a 3-, 4- or 5-star performance in 2021 had a lower Star Rating for 2022, despite average performance changes remaining relatively static (+1.0%, 0.0% and -0.2% for 3-, 4- or 5-stars respectively). These changes in SUPD performance
Figure 4: Calendar year 2021 to 2022 Star Ratings changes: Medication therapy management
highlight the unpredictability of CMS benchmarks year to year and the need for plans to make continual improvement efforts to maintain their Star Rating from the previous year. Only 28.9% of plans received a 4- or 5-Star for measurement year 2022. Conversely, 48.2% of plans received 1 or 2 Stars.
The changes outlined at the individual part D measure level translated into significant changes in the Part D summary rating for MAPD plans. More than 75% of plans with a 5-Star summary rating in 2021 did not maintain 5 Stars in 2022. Similar trends were observed for 4- and 4.5-Star plans — 44.8% and 56.7% saw lower summary part D Star ratings. Conversely, 100% of 1.5and 2-Star plans were able to improve from 2021 to 2022. This trend was also observed in 2.5- and 3-Star plans, of which 69.2% and 50%, respectively, saw improvements. Only 26.7% of 4-Star plans and 18.3% of 4.5-Star plans saw improvements year-overyear. This reinforces the notion that lower-performing plans have more opportunity for upward mobility, while higher-performing
plans face challenges in retaining their prior year Star ratings. The distribution of part D summary Star ratings saw relatively insignificant changes.
Likely the most important metric for MAPD plans is their overall Star rating, given CMS assesses this rating for various incentives. The trends reviewed at the measure level and in the part D summary rating also were observed in the overall Star rating. More than 60% of 5-Star plans did not retain a 5-Star rating from measurement year 2021 to 2022. Additionally, nearly 50% of 4and 4.5-Star plans also fell in overall Star rating.
As noted, only plans with an overall Star rating of 4 Stars or higher are eligible for quality bonus payments from CMS. From 2021 to 2022, more than 10% of 4.5-Star plans did not retain their eligibility to receive bonus payments in addition to 47.9% of 4-Star plans. High-performing plans again saw limited upward mobility — only 13.5% of 4-Star and 7.7% of 4.5-Star plans improved year-over-
year. Low-performing plans showed the greatest improvement, as 100% of 2-Star plans and more than 70% of 2.5-Star plans rose in their overall rating. The distribution of 5-Star plans dropped nearly 50% from 12.5% of plans to just 6.3%, while other distributive changes were relatively less drastic.
The uncertainty and volatility of individual part D measure cut points seem to directly impact the overall Star Rating performance for MAPD plans. High-performing plans, at both the measure and overall Star Rating level, tend to face headwinds in maintaining or improving their performance year to year. This highlights the need for ongoing resource investment in clinical measures to maintain or improve overall ratings year to year. In contrast with low-performing plans’ ability to quickly improve, there will be less opportunity for continuous improvement as plans reach the upper thresholds of measure performance.
Prime Therapeutics has a dedicated clinical team focused on improving performance at the individual Star measure level. By taking a focused approach, the Star clinical team aims to boost plans’ overall performance by increasing measure performance.
Note: The Centers for Medicare & Medicaid Services unexpectedly released updated 2024 Star (2022 measurement year) thresholds and national data at the beginning of July 2024. We are currently in the process of analyzing this information and will update this article once the results are available.
Find the complete guidelines at NCCN.org or visit
WARNING: QT PROLONGATION, TORSADES DE POINTES, and CARDIAC ARREST
• VANFLYTA® (quizartinib) prolongs the QT interval in a dose- and concentration-related manner. Prior to VANFLYTA administration and periodically, monitor for hypokalemia or hypomagnesemia, and correct deficiencies. Perform electrocardiograms (ECGs) to monitor the QTc at baseline, weekly during induction and consolidation therapy, weekly for at least the first month of maintenance, and periodically thereafter.
• Torsades de pointes and cardiac arrest have occurred in patients receiving VANFLYTA. Do not administer VANFLYTA to patients with severe hypokalemia, severe hypomagnesemia, or long QT syndrome.
• Do not initiate treatment with VANFLYTA or escalate the VANFLYTA dose if the QT interval corrected by Fridericia’s formula (QTcF) is greater than 450 ms.
• Monitor ECGs more frequently if concomitant use of drugs known to prolong the QT interval is required.
• Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure.
• Because of the risk of QT prolongation, VANFLYTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the VANFLYTA REMS.
VANFLYTA is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)–positive as detected by an FDA-approved test.
Limitations of Use:
Please see Brief PI Summary, including Boxed WARNINGS.
VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated.
FLT3=FMS-like tyrosine kinase 3; ITD=internal tandem duplication; NCCN=National Comprehensive Cancer Network. Reference: Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.2.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed April 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
VANFLYTA® (quizartinib) tablets, for oral use
Initial U.S. Approval: 2023
BRIEF SUMMARY: Please see package insert for full prescribing information.
• VANFLYTA prolongs the QT interval in a dose- and concentration-related manner [see Clinical Pharmacology (12.2) in the full prescribing information]. Prior to VANFLYTA administration and periodically, monitor for hypokalemia or hypomagnesemia, and correct deficiencies. Perform ECGs to monitor the QTc at baseline, weekly during induction and consolidation therapy, weekly for at least the first month of maintenance, and periodically thereafter [see Dosage and Administration (2.3) in the full prescribing information and Warnings and Precautions (5.1)].
• Torsades de pointes and cardiac arrest have occurred in patients receiving VANFLYTA. Do not administer VANFLYTA to patients with severe hypokalemia, severe hypomagnesemia, or long QT syndrome [see Contraindications (4) and Warnings and Precautions (5.1)]
• Do not initiate treatment with VANFLYTA or escalate the VANFLYTA dose if the QT interval corrected by Fridericia’s formula (QTcF) is greater than 450 ms [see Dosage and Administration (2.3) in the full prescribing information and Warnings and Precautions (5.1)]
• Monitor ECGs more frequently if concomitant use of drugs known to prolong the QT interval is required [see Dosage and Administration (2.3) in the full prescribing information and Warnings and Precautions (5.1)]
• Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure [see Dosage and Administration (2.4) in the full prescribing information and Warnings and Precautions (5.1)].
• Because of the risk of QT prolongation, VANFLYTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the VANFLYTA REMS [see Warnings and Precautions (5.2)].
1 INDICATIONS AND USAGE
VANFLYTA is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive as detected by an FDAapproved test [see Dosage and Administration (2.1) and Clinical Studies (14) in the full prescribing information]
Limitations of Use
VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated [see Clinical Studies (14) in the full prescribing information].
4 CONTRAINDICATIONS
VANFLYTA is contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes [see Warnings and Precautions (5.1)]
5 WARNINGS AND PRECAUTIONS
5.1 QT Prolongation, Torsades de Pointes, and Cardiac Arrest
VANFLYTA prolongs the QT interval in a dose- and concentration-dependent manner. The mechanism of QTc interval prolongation is via inhibition of the slow delayed rectifier potassium current, IKs, as compared to all other medications that prolong the QTc interval, which is via the rapid delayed rectifier potassium current, IKr. Therefore, the level of QTc prolongation with VANFLYTA that predicts the risk of cardiac arrhythmias is unclear. Inhibition of IKs and IKr may leave patients with limited reserve leading to a higher risk of QT prolongation and serious cardiac arrhythmias, including fatal outcomes [see Clinical Pharmacology (12.2) in the full prescribing information] Torsades de pointes, ventricular fibrillation, cardiac arrest, and sudden death have occurred in patients treated with VANFLYTA.
Of the 1,081 patients with AML treated with VANFLYTA in clinical trials, torsades de pointes occurred in approximately 0.2% of patients, cardiac arrest occurred in 0.6%, including 0.4% with a fatal outcome, and 0.1% of patients experienced ventricular fibrillation [see Adverse Reactions (6.1)] These severe cardiac arrhythmias occurred predominantly during the induction phase.
Of the 265 patients with newly diagnosed FLT3-ITD-positive AML treated with VANFLYTA in combination with chemotherapy in the clinical trial, 2.3% were found to have a QTcF greater than 500 ms and 10% of patients had an increase from baseline QTcF greater than 60 ms. The clinical trial excluded patients with a QTcF ≥450 ms or other factors that increased the risk of QT prolongation or arrhythmic events (e.g., NYHA Class III or IV
congestive heart failure, hypokalemia, family history of long QT interval syndrome). Therefore, avoid use in patients who are at significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, highdegree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism.
Do not initiate treatment with VANFLYTA if the QTcF interval is greater than 450 ms. Do not use VANFLYTA in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes [see Contraindications (4)]
Perform an ECG and correct electrolyte abnormalities prior to initiation of treatment with VANFLYTA. During induction and consolidation, perform an ECG prior to initiation and then once weekly during VANFLYTA treatment or more frequently as clinically indicated. During maintenance, perform ECGs prior to initiation, once weekly for at least the first month following dose initiation and escalation, and as clinically indicated thereafter. Do not escalate the dose if QTcF is greater than 450 ms [see Dosage and Administration (2.3) in the full prescribing information]
Perform ECG monitoring of the QT interval more frequently in patients who are at significant risk of developing QT interval prolongation and torsades de pointes, or following dose escalation.
Monitor and correct hypokalemia and hypomagnesemia prior to and during treatment with VANFLYTA. Maintain electrolytes in the normal range. Monitor electrolytes and ECGs more frequently in patients who experience diarrhea or vomiting.
Monitor patients more frequently with ECGs if coadministration of VANFLYTA with drugs known to prolong the QT interval is required [see Drug Interactions (7)]
Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure [see Dosage and Administration (2.4) in the full prescribing information]
Reduce VANFLYTA if QTc increases to greater than 480 ms and less than 500 ms. Interrupt and reduce VANFLYTA if QTc increases to greater than 500 ms. Permanently discontinue VANFLYTA in patients who develop recurrent QTc greater than 500 ms or QTc interval prolongation with signs or symptoms of life-threatening arrhythmia [see Dosage and Administration (2.3) in the full prescribing information]
VANFLYTA is available only through a restricted program under a REMS [see Warnings and Precautions (5.2)].
5.2 VANFLYTA REMS
VANFLYTA is available only through a restricted distribution program under a REMS called the VANFLYTA REMS because of the serious risk of QT prolongation, torsades de pointes, and cardiac arrest [see Warnings and Precautions (5.1)]
Notable requirements of the VANFLYTA REMS include the following:
• Prescribers must be certified in the VANFLYTA REMS by enrolling and completing training.
• Prescribers must counsel patients receiving VANFLYTA about the risk of QT prolongation, torsades de pointes, and cardiac arrest, and provide patients with a Patient Wallet Card.
• Pharmacies that dispense VANFLYTA must be certified with the VANFLYTA REMS and must verify prescribers are certified through the VANFLYTA REMS.
Further information about the VANFLYTA REMS is available at www.VANFLYTAREMS.com or by telephone at 1-855-212-6670.
5.3 Embryo-Fetal Toxicity
Based on findings in animals and its mechanism of action, VANFLYTA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of quizartinib to pregnant rats during organogenesis at exposures 3 times the maximum recommended human dose (MRHD) of 53 mg/day caused structural abnormalities and alterations to growth.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with VANFLYTA and for 7 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with VANFLYTA and for 4 months after the last dose [see Use in Specific Populations (8.1, 8.3)]
6 ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
• QT Prolongation, Torsades de Pointes, and Cardiac Arrest [see Warnings and Precautions (5.1)]
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of VANFLYTA (35.4 mg orally once daily with chemotherapy, 26.5 mg to 53 mg orally once daily as maintenance) in adult patients with newly diagnosed FLT3-ITD positive AML is based on QuANTUM-First, a randomized, double-blind clinical trial of VANFLYTA (n=265) or placebo (n=268) with chemotherapy [see Clinical Studies (14) in the full prescribing information]. Among patients who received VANFLYTA, 38% were exposed for 6 months or longer and 30% were exposed for greater than one year. On the VANFLYTA plus chemotherapy arm, 65% and 44% of patients completed induction and consolidation therapy, respectively, compared to 65% and 34% of patients in the placebo plus chemotherapy arm.
Serious adverse reactions in ≥5% of patients who received VANFLYTA plus chemotherapy were: febrile neutropenia (11%). Fatal adverse reactions occurred in 10% of patients who received VANFLYTA plus chemotherapy, including sepsis (5%), fungal infections (0.8%), brain edema (0.8%), and one case each of febrile neutropenia, pneumonia, cerebral infarction, acute respiratory distress syndrome, pulmonary embolism, ventricular dysfunction, and cardiac arrest.
Permanent discontinuation due to an adverse reaction in patients in the VANFLYTA plus chemotherapy arm occurred in 20% of patients. The most frequent (≥2%) adverse reaction which resulted in permanent discontinuation in the VANFLYTA arm was sepsis (5%).
Dosage interruptions of VANFLYTA due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage interruption in ≥2% of patients in the VANFLYTA arm included neutropenia (11%), thrombocytopenia (5%), and myelosuppression (3%).
Dose reductions of VANFLYTA due to an adverse reaction occurred in 19% of patients. Adverse reactions which required dosage reductions in ≥2% of patients in the VANFLYTA arm were neutropenia (9%), thrombocytopenia (5%), and electrocardiogram QT prolonged (4%).
The most common adverse reactions (≥10% with a difference between arms of ≥2% compared to placebo), including laboratory abnormalities, were lymphocytes decreased, potassium decreased, albumin decreased, phosphorus decreased, alkaline phosphatase increased, magnesium decreased, febrile neutropenia, diarrhea, mucositis, nausea, calcium decreased, abdominal pain, sepsis, neutropenia, headache, creatine phosphokinase increased, vomiting, upper respiratory tract infections, hypertransaminasemia, thrombocytopenia, decreased appetite, fungal infections, epistaxis, potassium increased, herpesvirus infections, insomnia, electrocardiogram QT prolonged, magnesium increased, sodium increased, dyspepsia, anemia, and eye irritation.
Tables 5 and 6 summarize adverse reactions and laboratory abnormalities observed in patients receiving VANFLYTA in the clinical trial.
Table 5: Adverse Reactions (≥10%) in Patients with Newly Diagnosed FLT3-ITD positive AML Who Received VANFLYTA (with a Difference Between Arms of ≥2% Compared to Placebo) in the Clinical Trial
Body System
Adverse Reaction VANFLYTA + Chemotherapy (N=265)
Grade 3 or 4
Blood and Lymphatic System Disorders
Febrile
Neutropenia†
Gastrointestinal Disorders
Table 5: Adverse Reactions (≥10%) in Patients with
Body System
* Including fatalities.
† Includes other related terms.
a Diarrhea includes colitis, diarrhea, enteritis, enterocolitis, gastroenteritis, and neutropenic colitis.
b Mucositis includes anal inflammation, anal ulcer, anorectal discomfort, aphthous ulcer, laryngeal inflammation, laryngeal pain, mucosal inflammation, edema mucosal, esophageal pain, esophageal ulcer, esophagitis, oral blood blister, oral disorder, oral mucosa erosion, oral mucosal blistering, oral mucosal erythema, oral pain, oropharyngeal pain, pharyngeal inflammation, proctalgia, proctitis, stomatitis, tongue ulceration, and vaginal ulceration.
c Sepsis includes acinetobacter infection, bacteremia, bacterial sepsis, corynebacterium bacteremia, device related bacteremia, device related sepsis, enterobacter sepsis, enterococcal bacteremia, enterococcal sepsis, escherichia bacteremia, escherichia sepsis, klebsiella bacteremia, klebsiella sepsis, neutropenic sepsis, pseudomonal bacteremia, pulmonary sepsis, sepsis, septic shock, staphylococcal bacteremia, staphylococcal infection, staphylococcal sepsis, stenotrophomonas sepsis, streptococcal sepsis, and streptococcal bacteremia.
d Fungal infection includes aspergillosis oral, aspergillus infection, bronchopulmonary aspergillosis, candida infection, candida sepsis, fungal infection, fungal sepsis, fungal skin infection, fusarium infection, gastrointestinal candidiasis, hepatic infection fungal, hepatosplenic candidiasis, lower respiratory tract infection fungal, mucormycosis, oral candidiasis, oral fungal infection, oropharyngeal candidiasis, systemic candida, systemic mycosis, tinea cruris, and vulvovaginal candidiasis.
e Herpesvirus infection includes disseminated varicella zoster virus infection, genital herpes, herpes simplex, herpesvirus infection, herpes zoster, oral herpes, and varicella zoster virus infection.
f Hypertransaminasemia includes alanine aminotransferase increased, aspartate aminotransferase increased, transaminases increased, hepatic enzymes increased, and hypertransaminasemia.
g Eye irritation includes dry eye, eye inflammation, eye irritation, eye pain, eye pruritus, foreign body sensation in eyes, keratitis, and ulcerative keratitis.
Laboratory Abnormalities
Prolonged thrombocytopenia or neutropenia in the absence of active leukemia lasting past cycle day 42 of induction cycle 1 were noted in 8% of patients on the VANFLYTA plus chemotherapy arm and 4% of patients in the placebo plus chemotherapy arm.
Table 6: Select Laboratory Abnormalities (≥10%) That Worsened from Baseline in Patients with Newly Diagnosed FLT3-ITD positive AML (with a Difference Between Arms of ≥2% Compared to Placebo) in the Clinical Trial
Laboratory Abnormality
VANFLYTA + Chemotherapy* PLACEBO + Chemotherapy* All Grades
Grades 3 or 4
Sodium
*The denominator used to calculate the rate varied from 199 to 260 in VANFLYTA + Chemotherapy and from 187 to 267 in PLACEBO + Chemotherapy based on the number of patients with a baseline value and at least one posttreatment value.
Other Clinical Trials
Clinically relevant adverse reactions in <10% of patients who received quizartinib for relapsed or refractory FLT3-ITD positive AML, an indication for which VANFLYTA is not approved, included differentiation syndrome (5%) and acute febrile neutrophilic dermatosis (3%).
7 DRUG INTERACTIONS
Table 7: Effect of Other Drugs on VANFLYTA
Strong CYP3A Inhibitors
Clinical Impact
VANFLYTA is a CYP3A substrate. Concomitant use of VANFLYTA with a strong CYP3A inhibitor increases quizartinib systemic exposure [see Clinical Pharmacology (12.3) in the full prescribing information], which may increase the risk of VANFLYTA adverse reactions.
Prevention or Management Reduce the dosage of VANFLYTA [see Dosage and Administration (2.4) in the full prescribing information]
Strong or Moderate CYP3A Inducers
Clinical Impact
Concomitant use of VANFLYTA with strong or moderate CYP3A inducers decreases quizartinib systemic exposure [see Clinical Pharmacology (12.3) in the full prescribing information], which may reduce VANFLYTA efficacy.
Prevention or Management Avoid concomitant use of VANFLYTA with strong or moderate CYP3A inducers [see Clinical Pharmacology (12.3) in the full prescribing information]
QT Interval Prolonging Drugs
VANFLYTA prolongs the QT/QTc interval.
Clinical Impact
Prevention or Management
Coadministration of VANFLYTA with other drugs that prolong the QT interval may further increase the incidence of QT prolongation [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) in the full prescribing information]
Monitor patients more frequently with ECG if coadministration of VANFLYTA with drugs known to prolong the QT interval is required. Examples of QT prolonging drugs include but are not limited to antifungal azoles, ondansetron, granisetron, azithromycin, pentamidine, doxycycline, moxifloxacin, atovaquone, prochlorperazine, and tacrolimus.
Based on findings from animal studies and its mechanism of action, VANFLYTA can cause embryo-fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) in the full prescribing information]
There are no available data on VANFLYTA use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, oral administration of quizartinib to pregnant rats during organogenesis resulted in adverse developmental outcomes including structural abnormalities and alterations to growth at maternal exposures approximately 3 times those in patients at the maximum recommended human dose (MRHD) of 53 mg/day (see Data) Advise pregnant women of the potential risk to a fetus.
The background risk in the U.S. general population of major birth defects is 2-4%, and of miscarriage is 15-20% of clinically recognized pregnancies.
Data
Animal Data
In an embryo-fetal development study in rats, pregnant animals received oral doses of quizartinib of 0, 0.6, 2, or 6 mg/kg/day during the period of organogenesis. Administration of quizartinib at the dose of 6 mg/kg/day was associated with adverse developmental outcomes including structural abnormalities (anasarca and edema) and alterations to growth (lower fetal weights and effects on skeletal ossification). At this dose, the maternal systemic exposures (AUC) were approximately 3 times the human exposure at the MRHD of 53 mg/day.
8.2 Lactation
Risk Summary
There are no data on the presence of quizartinib or its metabolites in human milk, or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with VANFLYTA and for one month after the last dose.
8.3 Females and Males of Reproductive Potential
VANFLYTA can cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)]
Pregnancy Testing
Verify pregnancy status in females of reproductive potential within seven days before starting treatment with VANFLYTA.
Contraception
Females
Advise female patients of reproductive potential to use effective contraception during treatment with VANFLYTA and for 7 months after the last dose.
Males
Based on genotoxicity findings, advise male patients with female partners of reproductive potential to use effective contraception during treatment with VANFLYTA and for 4 months after the last dose [see Nonclinical Toxicology (13.1) in the full prescribing information]
Infertility
Females
Based on findings from animal studies, VANFLYTA may impair female fertility. These effects on fertility were reversible [see Nonclinical Toxicology (13.1) in the full prescribing information]
Males
Based on findings from animal studies, VANFLYTA may impair male fertility. These effects on fertility were reversible [see Nonclinical Toxicology (13.1) in the full prescribing information]
8.4 Pediatric Use
Safety and effectiveness of VANFLYTA have not been established in pediatric patients.
8.5 Geriatric Use
There were 533 patients with newly diagnosed AML in the clinical study; of the total number of VANFLYTA-treated patients, 69 (26%) were 65 years of age and older, while 1 (0.4%) was 75 years of age [see Clinical Studies (14) in the full prescribing information]. No overall differences in safety or efficacy were observed between patients 65 years of age and older and younger adult patients.
8.6 Renal Impairment
No dosage adjustment is recommended in patients with mild to moderate renal impairment (i.e., estimated creatinine clearance [CLcr] by CockcroftGault equation: CLcr 30 to 89 mL/min). VANFLYTA has not been studied in patients with severe renal impairment (CLcr <30 mL/min) [see Clinical Pharmacology (12.3) in the full prescribing information]
8.7 Hepatic Impairment
No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Class A or total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase [AST] >ULN, or total bilirubin >1 to 1.5 times ULN and any value for AST) or moderate hepatic impairment (Child-Pugh Class B or total bilirubin >1.5 to 3 times ULN and any value for AST). VANFLYTA has not been studied in patients with severe (Child-Pugh Class C or total bilirubin >3 times ULN and any value for AST) hepatic impairment [see Clinical Pharmacology (12.3) in the full prescribing information]
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
QT Prolongation, Torsades de Pointes, and Cardiac Arrest
Inform patients of symptoms that may be associated with significant QTc interval prolongation including dizziness, lightheadedness, and fainting. Advise patients to report these symptoms and the use of all medications to their healthcare provider [see Warnings and Precautions (5.1)]
VANFLYTA REMS
VANFLYTA is available only through a restricted program called the VANFLYTA REMS. Inform patients that they will be given a VANFLYTA Patient
Wallet Card that they should carry with them at all times and show to all of their healthcare providers. This card describes signs and symptoms related to QT prolongation/cardiac arrhythmia which, if experienced, should prompt the patient to immediately seek medical attention [see Warnings and Precautions (5.2)]
Drug Interactions
Advise patients to inform their healthcare providers of all concomitant medications, including over-the-counter medications, vitamins, and herbal products. Advise patients to avoid concomitant use of St. John’s wort as it is a strong CYP3A inducer [see Drug Interactions (7)]
Embryo-Fetal Toxicity and Use of Contraceptives
Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with VANFLYTA and for 7 months after the last dose. Advise
patients to notify their healthcare provider immediately in the event of a pregnancy or if pregnancy is suspected during VANFLYTA treatment. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with VANFLYTA and for 4 months after the last dose [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1, 8.3)].
Infertility
Advise females and males of reproductive potential that VANFLYTA may impair fertility [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1) in the full prescribing information]
Lactation
Advise women not to breastfeed during treatment with VANFLYTA and for one month after the last dose [see Use in Specific Populations (8.2)]
Dosing and Storage Instructions
• Advise patients that VANFLYTA should be taken once daily at approximately the same time each day and may be taken with or without food.
• Advise patients to swallow tablets whole. Advise patients not to cut, crush, or chew the tablets [see Dosage and Administration (2.2) in the full prescribing information].
• Instruct patients that if a dose of VANFLYTA is vomited, not to take an additional dose that day, and to wait until the next scheduled dose on the following day. If a dose of VANFLYTA is missed or not taken at the usual time, instruct patients to take the dose as soon as possible on the same day and return to the usual dosing schedule the following day.
• Store VANFLYTA at room temperature from 20°C to 25°C (68°F to 77°F).
Manufactured for:
Daiichi Sankyo, Inc., Basking Ridge, NJ 07920
VANFLYTA® is a registered trademark of Daiichi Sankyo Company, Ltd.
Copyright © 2023, Daiichi Sankyo, Inc.
USPI-VAN-C1-0723-r001
SVP, Government Programs
Prime Therapeutics
Lori
Pharm.D. Consultant, Inflation Reduction Act
Prime Therapeutics
The Inflation Reduction Act (IRA) was signed into law in August 2022 and includes a wide range of provisions aimed at encouraging clean energy, increasing tax revenue and reducing health care costs.1 The Medicare changes in the IRA are specifically targeted toward lowering prescription drug costs for beneficiaries enrolled in Medicare Part D (Part D) and have multi-year implications for Part D plans, including:2, 3
• Expansion of the Medicare low-income subsidy
• Stabilization of Part D premiums
• Reduced patient copays for insulin and vaccines
• Part D cost-share redesign with lower patient costs
• Price negotiations with drug manufacturers
• Limitations on manufacturer drug price increases
The IRA also created the Medicare Prescription Payment Plan (M3P), which requires Part D plans to offer their enrollees the option to pay for prescriptions in monthly installments instead of at the pharmacy counter. The M3P is most beneficial to patients who have high prescription drug costs early in the year.4
This article provides a summary of the main Part D provisions from the IRA, identifies challenges Part D plans may face as a result of the IRA and provides suggestions for overcoming those challenges and avoiding potential landmines.
The Medicare Low-Income Subsidy (LIS) lowers or removes Part D costs for individuals and couples with limited resources. Starting January 2024, the IRA increased the threshold for LIS eligibility to 150% of the federal poverty level (FPL). The Centers for Medicare & Medicaid Services (CMS) estimates that this change provides LIS to approximately 300,000 more beneficiaries compared to the previous threshold of 135% FPL.3
The IRA includes a provision to stabilize Medicare Part D premiums by limiting the increase in the base beneficiary premium (BBP) to 6% each year. This program started in 2024 and is intended to protect Medicare beneficiaries from large Part D premium increases.5
This program does not limit how much individual plans can increase their premiums. Instead, CMS first calculates the annual BBP using the national average bid amount and the amount of CMS reinsurance payments. CMS then subsidizes year-over-year BBP increases of greater than 6% and distributes the subsidy equally across all plans. Figure 8 provides an example of how the BBP subsidy is applied.6
Figure 8: In this example, the plan premium increased by 33%, but the Premium Stabilization subsidy reduced the member’s increase to 18%.
Lowering patient costs for insulin and vaccines was one of the earliest provisions implemented by the IRA. Prior to the IRA, Part D plans had the flexibility to require a higher patient cost-share aligned with the copay or coinsurance for the formulary tier assigned to each insulin or vaccine product.
Starting in 2023, the IRA removed the patient’s deductible cost for insulin and created a maximum copay, set by CMS, for insulin products covered under Medicare. Currently, the maximum copay is set at $35 for a one-month supply of insulin, but is subject to change on an annual basis. The IRA includes a similar provision for insulin used in an insulin pump and covered by Medicare Part B.7 Approximately four million Medicare beneficiaries are expected to benefit from this change.3
The IRA also requires Part D plans to bypass the deductible and provide their members most adult vaccines for no out-of-pocket cost. All adult vaccines covered under Part D and recommended by the Advisory Committee on Immunization Practices (ACIP) are included in this requirement.8
$30.00
$25.00
$20.00
$15.00
Before the IRA, Part D coverage consisted of four benefit phases:9
1. The deductible phase, where patients are responsible for 100% of their drug costs
2. The initial coverage phase, where patients are responsible for their drug-specific copay or coinsurance
3. The coverage gap phase, where patients are responsible for 25% of their drug costs and manufacturers are responsible for 70% of brand name drug costs
4. The catastrophic coverage phase, where patients are responsible for 5% and CMS is responsible for 80% of drug costs
In all four coverage phases, the Part D plan is responsible for the remainder of the drug costs. Each year, CMS defines standardized cost thresholds for each coverage phase. When a patient’s drug costs reach the threshold for their current phase, they transition into the next phase. Table 10 provides the 2023 and 2024 cost thresholds defined by CMS.
The IRA includes several changes to the Part D coverage phases that redistribute Part D drug costs. These changes started in 2024, when the IRA maintained the coverage gap but removed the 5% member coinsurance in the catastrophic coverage phase and reallocated those costs to Part D plans. For 2025 and beyond,
the IRA eliminates the coverage gap and adjusts the cost-share portions in the initial coverage and catastrophic phases.9, 11 Figure 9 provides a summary of changes to the Part D coverage structure for 2025 compared to 2024.
The Part D redesign also reduces the beneficiary out-of-pocket threshold to $2,000 in 2025 and includes changes to the costs that contribute to this threshold. Under the new design, supplemental coverage from enhanced alternatives plans, employer group waiver plans (EGWPs) and other health insurance count toward the out-of-pocket threshold. As a result, patients may reach the out-of-pocket threshold without spending the full $2,000.12
Manufacturer price negotiations and inflation rebates
Manufacturer price negotiations under the IRA mark the first time Medicare has the authority to negotiate prices with drug manufacturers. The program focuses on high-cost, high-volume, single-source drugs covered under Medicare Parts B or D.13
In 2023, CMS chose 10 Part D drugs for the first group of negotiations. CMS and the manufacturers have determined a maximum fair price (MFP) for each drug, which will be released
September 1, 2024, and become effective January 1, 2026. The IRA also requires all Part D plans to include these drugs on their 2026 formularies. CMS will add additional drugs and expand the list to include Part B drugs in upcoming years.13
For drugs not included in manufacturer price negotiations, the IRA limits year-over-year price increases to no higher than the rate of inflation. This provision applies to drugs covered under both Part D and Part B. Manufacturers that raise drug prices faster than the rate of inflation are required to pay rebates to CMS, although rebates are waived if the drug is impacted by shortages or severe supply chain disruption.14
Originally called “copay smoothing,” the Medicare Prescription Payment Plan (M3P) allows Part D members the option to pay out-of-pocket drug costs in monthly payments instead of at the pharmacy counter starting January 1, 2025. Figure 10 provides a high-level overview of the M3P process.
M3P requires Part D plans to:15
• Make M3P available to all members
• Educate their members about the availability of the program
• Include all Part D covered drugs
• Notify pharmacies when a member is likely to benefit from the program
• Provide processes for members to opt in using paper, telephone or website
• Invoice participating members on a monthly basis using mandated calculations
• Pay pharmacies in full, including the member portion of the cost
• Have an appeals and dispute process in place
Part D plans can remove members from the M3P program after a two-month grace period if they do not pay their M3P invoices, but they cannot disenroll those members from the plan.15 Since M3P is a new program with no historical data for participation rates, it will be initially difficult for plans to estimate the cost of M3P bad debt.
While the M3P allows members to pay for drug costs from a monthly invoice instead of at the pharmacy counter, the mandated calculations do not result in equal monthly installments. Not all members will benefit from participating in M3P, and the monthly invoice calculations vary based on the timing of M3P election and prescription costs.16 CMS has determined that members with at least $2,000 in annual out-of-pocket drug costs or a single prescription with at least $600 copay/coinsurance are the most likely to benefit from M3P.15
CMS requires Part D plans to provide several forms of outreach to educate their members about the M3P. Plans are required to list general information about M3P availability on their website, when sending ID card mailings and as part of annual enrollment materials such as the Evidence of Coverage (EOC) and the Annual Notice of Change (ANOC). Prior to each plan year, Part D plans must also send targeted information during the fourth quarter to members with at least $2,000 in out-of-pocket drug costs during the first three quarters of the year. During the plan year, pharmacy
benefit managers (PBMs) must provide claims messaging to notify dispensing pharmacies when a member’s prescription meets the $600 threshold, and the pharmacies are responsible for providing M3P information to the patient. Also during the plan year, Part D plans are required to develop strategies for sending M3P materials to targeted members who are likely to benefit from the program.17
The IRA has multiple financial and operational impacts on Part D plans. More LIS members, higher plan cost-share for insulin and vaccines and increased plan liability from the IRA Part D redesign contribute to clinical costs, while M3P administration and unpaid invoices contribute to operational costs. The IRA will affect almost every area of Part D plans and their PBMs. Organizations must make a concerted effort to educate involved parties and encourage new ways of thinking for successful execution. Table 11 provides a list of areas likely to be impacted by IRA changes.
The Part D Redesign includes changes that may create challenges for enhanced benefits. Plans can no longer offer improved costsharing in the coverage gap or catastrophic coverage phases as part of their enhanced offerings. Additionally, both formulary and benefit components of enhanced plans must be at least equivalent to basic coverage in order to achieve a meaningful difference.12
While the M3P will improve access and affordability to beneficiaries with high out-of-pocket drug costs,4 not all members will benefit from this program. Members who are unlikely to benefit but who opt into M3P anyway may be unhappy with their monthly invoice amounts. To avoid complaints, Part D plans should make extensive educational efforts to provide their members the information they need to make an informed decision before participating in M3P.
Timelines make the Part D bid implications from the IRA especially tricky for the 2025 bid. Some of the CMS guidance was only recently finalized, though some provisions will be effective for Medicare Open Enrollment on October 15, 2024. Compressed implementation timelines mean that many of the costs associated with various IRA provisions are still unknown, and there is no historical data available for M3P bad debt estimates.
Part D plans should be careful not to underestimate the scope and complexity of the IRA’s impact. While some IRA provisions involve minimal plan intervention, others require daunting operational changes and financial considerations. To allow
Operational area
adjudication/PBM
Member correspondence
Grievances and complaints
Pharmacy network
Provider network
Contact center/customer service
Accounting and ledgering
Actuarial services and bid support
Information technology
Possible IRA considerations
• Insulin and vaccine copays
adequate time for implementation and testing, Part D plans and PBMs should start planning for IRA changes without waiting for final CMS guidance.
Implementing M3P will be especially complicated, with requirements and responsibilities spread across Part D plans, PBMs and dispensing pharmacies. To avoid member confusion and complaints, Part D plans will need robust M3P training and educational materials for internal staff, providers, pharmacies and members.
Overall, Part D plans should work closely with their PBMs and other partners to develop and execute IRA implementation plans. Planning, collaboration and flexibility will provide the best opportunity for a successful execution of IRA requirements.
• Part D redesign coverage phases and accumulator changes
• M3P claims and messaging
• Manufacturer MFPs
• M3P general information in EOC, ANOC and when sending member ID cards
• M3P targeted information to members in Q4
• Confirmation of M3P participation upon opt-in
• M3P monthly invoices, late payment notices and involuntary termination notices
• Unexpected M3P invoice amounts
• M3P disputes and adjustments
• Education for M3P claims and messaging
• M3P member education distribution requirements
• Contract changes and oversight
• Education about M3P availability
• Increased call volume due to IRA-related plan changes
• Education and materials for member calls regarding:
• Insulin and vaccine copay changes
• Cost changes from Part D redesign
• M3P general education and opt-ins
• M3P monthly calculations and invoice information
• M3P calculation and member invoices
• M3P payment collection
• M3P bad debt estimations
• Expanded availability of LIS
• Changes in plan liability for insulin and vaccines
• Increased plan liability from Part D redesign
• M3P operational and bad debt expenses
• Impacts to manufacturer rebates
• Adjustments to targeted populations and service areas
• Data sharing with PBM and/or M3P vendor
• New data fields for M3P participation
References
1. The Inflation Reduction Act: Here’s what’s in it. (2022, Oct. 24). McKinsey & Company. https://www.mckinsey.com/industries/ public-sector/our-insights/the-inflation-reduction-act-heres-whatsin-it
2. The Inflation Reduction Act Lowers Health Care Costs for Millions of Americans. Centers for Medicare & Medicaid Services. (2022, Oct. 4). https://www.cms.gov/priorities/legislation/inflation-reduction-actand-medicare/lowers-health-care-costs-millions-americans
3. Anniversary of the Inflation Reduction Act: Update on CMS Implementation. (2022, Aug. 16). Centers for Medicare & Medicaid Services. https://www.cms.gov/newsroom/fact-sheets/anniversaryinflation-reduction-act-update-cms-implementation
4. Fact Sheet: Medicare Prescription Payment Plan. (2023, Aug.). Centers for Medicare & Medicaid Services. https://www.cms.gov/files/ document/medicare-prescription-payment-plan-fact-sheet.pdf
5. CMS Releases 2024 Projected Medicare Part D Premium and Bid Information. (2023, July 31). Centers for Medicare & Medicaid Services. https://www.cms.gov/newsroom/fact-sheets/cmsreleases-2024-projected-medicare-part-d-premium-and-bidinformation
6. While the Premium Stabilization Program Under the IRA Limits the Growth of the Base Beneficiary Premium, Individual Plan Premiums Vary. (2023, Oct. 17). Avalere Health. https://avalere.com/insights/ part-d-premiums-increasing-despite-stabilization-program
7. Frequently Asked Questions about Medicare Insulin Cost-Sharing Changes in the Prescription Drug Law. (2023, Jan.). Centers for Medicare & Medicaid Services. https://www.cms.gov/files/ document/frequently-asked-questions-medicare-part-d-insulinbenefit.pdf
8. Contract Year 2023 Program Guidance Related to Inflation Reduction Act Changes to Part D Coverage of Vaccines and Insulin. (2022, Sept. 26). Centers for Medicare & Medicaid Services. https://www.cms. gov/files/document/irainsulinvaccinesmemo09262022.pdf
9. Changes to Medicare Part D in 2024 and 2025 Under the Inflation Reduction Act and how Enrollees Will Benefit. (2023, April 20). Kaiser Family Foundation. https://www.kff.org/medicare/issuebrief/changes-to-medicare-part-d-in-2024-and-2025-under-theinflation-reduction-act-and-how-enrollees-will-benefit
10. Announcement of Calendar Year (CY) 2024 Medicare Advantage (MA) Capitation Rates and Part C and Part D Payment Policies. (2023, March 31). Centers for Medicare & Medicaid Services. https://www. cms.gov/files/document/2024-announcement-pdf.pdf
11. 2025 Part D Risk Adjustment Model Update User Group. (2023, Sept. 25). Centers for Medicare & Medicaid Services. https://www.hhs. gov/guidance/document/2025-part-d-risk-adjustment-modelupdate-user-group-slide-deck
12. Draft CY 2025 Part D Redesign Program Instructions. (2024, Jan. 31). Centers for Medicare & Medicaid Services. https://www.cms.gov/ sites/default/files/2024-01/Draft%20CY%202025%20Part%20 D%20Redesign%20Program%20Instructions_January%2031%20 2024_Final_Updated.pdf
13. Fact Sheet: Medicare Drug Price Negotiation Program Revised Guidance. (2023, June 30). Centers for Medicare & Medicaid Services. https://www.cms.gov/files/document/fact-sheetreviseddrug-price-negotiation-program-guidance-june-2023.pdf
14. Fact Sheet: Medicare Prescription Drug Inflation Rebate Program Revised Guidance. (2023, Dec. 14). Centers for Medicare & Medicaid Services. https://www.cms.gov/files/document/fact-sheetmedicare-prescription-drug-inflation-rebate-revised-guidance.pdf
15. Medicare Prescription Payment Plan: Final Part One Guidance on Select Topics, Implementation of Section 1860-D of the Social Security Act for 2025, and Response to Relevant Comments. (2024, Feb. 29). Centers for Medicare & Medicaid Services. https://www. cms.gov/files/document/medicare-prescription-payment-plan-finalpart-one-guidance.pdf
16. Technical Memorandum on the Calculation of the Maximum Monthly Cap on Cost-Sharing Payments Under Prescription Drug Plans. (2023, July 17). Centers for Medicare & Medicaid Services. https://www. cms.gov/files/document/monthly-cap-cost-sharing-technicalmemo-july-2023.pdf
17. Medicare Prescription Payment Plan: Final Part Two Guidance on Select Topics, Implementation of Section 1860D-2 of the Social Security Act for 2025, and Response to Relevant Comments. (2024, Jul. 16.) Centers for Medicare & Medicaid Services. https://www. cms.gov/files/document/medicare-prescription-payment-plan-finalpart-two-guidance.pdf
Roflumilast (Zoryve®) Arcutis Atopic dermatitis (ages > 6 years)
Naloxone
Deuruxolitinib Sun Pharmaceutical Industries Alopecia areata (moderate to severe)
Afamitresgene
Levodopa/carbidopa
Denileukin diftitox Citius Pharmaceuticals Cutaneous T-cell lymphoma
Nemolizumab Galderma Pruritus
Vorasidenib Servier Glioma (IDH-mutant diffuse)
Linvoseltamab Regeneron Pharmaceuticals MM (R/R, > fourth-line)
Dostarlimab-gxly (Jemperli) GlaxoSmithKline
cancer (primary advanced or recurrent, in combination with carboplatin/paclitaxel)
Axatilimab Syndax Pharmaceuticals GVHD (chronic, after failure of > two prior lines of systemic therapy)
Govorestat Applied Therapeutics Classic galactosemia
Sodium oxybate (Lumryz™) Avadel Pharmaceuticals
cataplexy or EDS (pediatrics)
Atezolizumab/hyaluronidase Genentech HCC; Melanoma; NSCLC; Urothelial cancer; SCLC; Soft tissue sarcoma
BLA; Fast track; Orphan drug; Priority review 08/28/2024
NDA; Fast track; Orphan drug; Priority review; RPD 08/28/2024
Amivantamab-vmjw
ustekinumab (biosimilar to Janssen’s Stelara®) Formycon
NSCLC (locally advanced or metastatic, EGFR exon 19 deletions or L858R substitution, in combination with chemotherapy after disease progression on or after osimertinib)
Nivolumab Bristol Myers Squibb NSCLC (resectable stage IIA to IIIB, neoadjuvant with chemotherapy followed by surgery and adjuvant to surgery)
Amivantamab-vmjw Johnson & Johnson Innovative Medicine
NSCLC (locally advanced or metastatic, EGFR exon 19 deletions or L858R substitution, first-line, in combination with lazertinib)
Ribociclib (Kisqali®) Novartis Breast cancer (adjuvant therapy)
iptacopan (Fabhalta®) Novartis
Immunoglobulin A (IgA) nephropathy (Berger’s disease)
Benralizumab (Fasenra®) AstraZeneca Anti-neutrophil cytoplasmic antibodies-associated vasculitis
Durvalumab (Imfinzi®) AstraZeneca Endometrial cancer (first-line, in combination with olaparib)
Olaparib (Lynparza®) AstraZeneca Endometrial cancer (first-line, in combination with durvalumab)
sNDA; seeking Accelerated Approval; Priority Review September-October 2024
July-December 2024
sNDA July-December 2024
Abbreviations: AD = Alzheimer’s disease; BLA = Biologics License Application; CD = Crohn’s disease; CML = chronic myelogenous leukemia; EDS = excessive daytime sleepiness; EGFR = epidermal growth factor receptor; GVHD = graft versus host disease; HCC = hepatocellular carcinoma; IDH = isocitrate dehydrogenase; IM = intramuscular; IV = intravenous; MM = multiple myeloma; MS = multiple sclerosis; NDA = new drug application; NSCLC = non-small cell lung cancer; PNH = paroxysmal nocturnal hemoglobinuria; PsA = psoriatic arthritis; PSO = psoriasis; PTSD = post-traumatic stress disorder; RMAT = Regenerative Medicine Advanced Therapy; RPD = Rare Pediatric Disease; R/R = relapsing or refractory; sBLA = supplemental Biologics License Application; SC = subcutaneous; SCLC = small cell lung cancer; sNDA = supplemental new drug application; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus; UC = ulcerative colitis