Magellan Rx Report - Fall 2021 by Prime/Magellan Rx

Magellan Rx Report Fall 2021

Atopic Dermatitis: Therapeutic Advances and Payer Impact

Lupus and Lupus Nephritis: Advances in Treatment and Management

Chronic Kidney Disease: Emerging Therapies and Management Strategies

Dry Eye Disease: Changing Treatment and Management Landscape

Magellan Rx Report MEDICAL AND PHARMACY BENEFIT MANAGEMENT Fall 2021

Alzheimer’s Disease: Treatment Update

magellanrx.com/mrxreport

IN THIS ISSUE | Fall 2021

Managed Care Newsstand

Atopic Dermatitis:

Therapeutic Advances and Payer Impact

29 34

Chronic Kidney Disease:

Emerging Therapies and Management Strategies

Magellan Capability Insight:

Enhanced Utilization Management Program for High-Cost Therapies

Lupus and Lupus Nephritis:

Dry Eye Disease:

19 24

Biosimilar Update and Pipeline

Pipeline

Advances in Treatment and Management

Changing Treatment and Management Landscape

Alzheimer’s Disease:

Treatment Update and Managed Care Implications

Published By Magellan Rx Management 4801 E. Washington St., Ste. 100 Phoenix, AZ 85034

Contributors Caroline Carney, M.D., M.Sc., FAPM, CPHQ

Tel: 401-344-1000 Fax: 401-619-5215

SVP, Market General Manager, MRx Specialty

CMO, Magellan Health, Magellan Rx Management

Steve Cutts, Pharm.D.

Haita Makanji, Pharm.D.

VP, Clinical Strategy and Innovation, Specialty

magellanrx.com

Misty Greficz

Editor Lindsay Speicher, J.D.

Project Manager, Magellan Method lspeicher@magellanhealth.com 401-344-1105

Advertising, Sales and Distribution Carole Kallas ckallas@magellanhealth.com 401-344-1132

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 RxTM 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.

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

Director, Marketing

Chief, Division of Rheumatology, Mount Sinai West; Professor of Medicine, Icahn School of Medicine at Mount Sinai

Joe Tavares

Steven L. D’Amato, B.S.Pharm.

Corrado Panno

Joseph Mikhael, M.D., M.Ed., FRCPC, FACP

Stacy Inman, Pharm.D.

Natalie Tate, Pharm.D., MBA, BCPS

SVP, Sales and Business Development, Specialty VP, Business Development, Magellan Method Senior Clinical Project Manager, Magellan Method

Carole Kallas Project Manager

Brian Kinsella, Esq. TM

Editorial Advisory Board Mona M. Chitre, Pharm.D., CGP

Senior Legal Counsel

Alina Young

Associate Legal Counsel

Executive Director, New England Cancer Specialists

Chief Medical Officer, International Myeloma Foundation VP, Pharmacy Management, BlueCross BlueShield of Tennessee

Steve Marciniak, R.Ph.

Director II, Medical Benefit Drug Management, BlueCross BlueShield of Michigan

Saira A. Jan, M.S., Pharm.D.

Director of Pharmacy Strategy and Clinical Integration, Horizon BlueCross BlueShield of New Jersey

Lilly Ackley

VP, Corporate Communications

Maria James

Director, External Communications

ISSN: 2159-5372

10444M

A NOTE FROM OUR CMO

Dear Managed Care Colleagues, Welcome to our fall 2021 issue of the Magellan Rx Report! This year has been exciting, with the first FDA approval of a COVID-19 vaccine and more than 200 million Americans having received at least one dose as of press time. Other healthcare spaces have seen innovation and advancement as well, with 35 novel therapy approvals and more anticipated before the end of the year. Magellan Rx Management is committed to providing our readers with trending clinical advances, approvals, and updates.

Other timely topics in this issue include updates on dry eye disease (page 37) and chronic kidney disease (page 29), a biosimilar pipeline (page 19), and a spotlight on Magellan’s Enhanced Utilization Management Program for High-Cost Therapies (page 34). As always, the issue is rounded out with our pipeline update (page 42) and managed care newsstand (page 2). To learn more about Magellan Rx Management and our support for payer initiatives of the future, please feel free to contact us at MagellanRxReport@magellanhealth.com. As always, we value any feedback you may have. I hope you enjoy the report! Sincerely,

Our cover story (page 24) focuses on Alzheimer’s disease and the long-awaited approval in this category, along with an expanded pipeline and the impact new treatment options may have for payers. In another article, we highlight the management of lupus and lupus nephritis (page 14). Two new approvals indicated for lupus nephritis will open more treatment options and require payers to strategize and manage the category effectively.

Caroline Carney, M.D., M.Sc., FAPM, CPHQ Chief Medical Officer Magellan Health & Magellan Rx Management

We outline the expanding treatment landscape for atopic dermatitis in another article (page 6), specifically the biologics in the pipeline anticipated over the next few years and how added treatment options may change management approaches.

SUBSCRIBE TODAY! Stay on top of managed care trends and become a Magellan Rx Report subscriber. Email us at MagellanRxReport@magellanhealth.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.

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MANAGED CARE NEWSSTAND Senate Finance Leaders Seek Ideas to Address Barriers to Mental Health Care Senate Finance Chairman Ron Wyden (D-OR) and ranking member Mike Crapo (R-ID) released a letter to Senate colleagues Sept. 21 seeking input from stakeholders across the healthcare continuum to help inform how Congress can address barriers to mental health care. While requesting ideas in all areas, the leaders asked for input around workforce shortages, access and care coordination issues, telehealth, and increasing access to behavioral healthcare for children and young people. The committee hopes to work on a bipartisan mental health bill over the remainder of the year.

New Federal Vaccine Requirements On Sept. 9, President Biden announced new federal vaccination requirements in the context of a new action plan: Path Out of the Pandemic. The vaccine rules will apply to federal workers, large employers, and healthcare staff. These new regulations are in response to the increased surge in COVID-19 cases across the nation.

Senators Release White Paper Reimagining Mental Health On Sept. 9, Sens. Michael Bennet (D-CO) and John Cornyn (R-TX) released a white paper, “A Bold Vision for America’s Mental Well-being,” which presents a framework for modernizing, reimagining, and redesigning the mental health and substance use disorder systems of care.

2 | Magellan Rx Report | Fall 2021

The white paper outlines key steps that Congress can take to improve both. The senators are seeking feedback and input “from experts, community leaders, and constituents on policies to help achieve intended outcomes laid out in their white paper.” They intend to use the feedback to “inform a forthcoming legislative package.”

HHS Secretary Xavier Becerra Releases Plan to Address Prescription Drug Costs The U.S. Department of Health and Human Services (HHS) released its Comprehensive Plan for Addressing High Drug Prices Sept. 9. The report responds to the request included in President Biden’s “Executive Order on Promoting Competition in the American Economy” for “a plan to continue the effort to combat excessive pricing of prescription drugs and enhance domestic pharmaceutical supply chains, to reduce the prices paid by the federal government for such drugs, and to address the recurrent problem of price gouging.” Overall, the report does not include any new policies. While the list of proposals is long, most include few details beyond discussion of the basic concepts that would need to be fleshed out via rule-making or collaboration with Congress. The report presents principles for equitable drug-pricing reform through competition, describes various congressional initiatives that are underway, and summarizes administrative actions and HHS proposals. The report outlines three guiding principles for HHS’ regulatory actions and legislative proposals relating to drug pricing. Each guiding principle includes specific legislative and regulatory recommendations. These align closely with the Biden administration’s Aug. 12 congressional priorities for prescription drug-pricing legislation.

While requesting ideas in all areas, the leaders asked for input around workforce shortages, access and care coordination issues, telehealth, and increasing access to behavioral healthcare for children and young people.

House Begins Markup of Build Back Better Act During the week of Sept. 7, committees of jurisdiction in the House of Representatives began to mark up portions of the Build Back Better Act, a plan that includes various pieces of President Biden’s American Jobs Plan and American Families Plan. The $3.5 trillion budget reconciliation package includes significant new investments in healthcare, child care, paid family and medical leave, higher education, workforce training, and more. It is being developed and considered pursuant to a

fiscal year 2022 budget resolution adopted in late August. This allows the Senate to pass the legislation by a simple majority and without being subject to a filibuster. Several House committees began marking up the draft legislation last week. The House intended to complete the process this week, aiming to have the full reconciliation package on the House floor for a vote by the end of the month. The Ways and Means Committee and the Energy and Commerce Committee proposals would phase in vision, hearing, and dental benefits in 2022, 2023, and 2028, respectively. The legislation would also make broad changes to prescription drug coverage under Medicare. In an attempt to address high prescription drug prices, the proposal includes the Elijah E. Cummings Lower Drug Costs Now Act (H.R. 3). It would require HHS to negotiate prices with drug manufacturers, require drug manufacturers that increase prices faster than inflation to pay back that excess amount to the government, and cap out-of-pocket costs for Medicare Part D beneficiaries at $2,000 per year. In addition, the legislation includes a repeal of the rebate rule. These proposals are a starting point in what is expected to be a rigorous budget reconciliation process. With narrow majorities in both chambers, Democrats are working to finalize the package quickly in hopes of moving it concurrently with the bipartisan infrastructure bill. Once the committees of jurisdiction have approved their legislation, the House Budget Committee and House Rules Committee will consider the bill before it is voted on by the full House. After the reconciliation package advances in the House, the Senate will begin its consideration.

CMS Releases Bulletin on Third Party Liability in Medicaid On Aug. 27, the U.S. Centers for Medicare & Medicaid Services (CMS) released a

Center Informational Bulletin to assist states in ensuring that their Medicaid state plans comply with Third Party Liability (TPL) requirements reflected in current laws. CMS notes that states should update their Medicaid TPL state plan pages and submit amendments to CMS to reflect the recent changes in law. As states make changes in their TPL programs, they will likely lead to implications for Medicaid-managed care plan contracts.

Congress Passes $3.5 Trillion Budget Resolution, Begins Developing Legislative Details The House of Representatives returned in the middle of August and passed a $3.5 trillion budget resolution Aug. 24, after days of internal negotiations within the House Democratic Caucus. The 220-212 vote came with only Democratic members in support. The budget resolution follows similar action by the U.S. Senate, which passed the bill on a 5049 partisan vote earlier in August. Key to the agreement in the House was that the budget resolution would move in tandem with the bipartisan infrastructure bill. Lawmakers must now work on developing the legislative details surrounding the broad instructions contained in the budget resolution, which calls for extended subsidies of the Affordable Care Act (ACA) and the childcare tax credit that was passed earlier this year; universal pre-K and free community college; funding to combat climate change; committees to develop legislation to provide dental, vision, and hearing benefits in Medicare, reform the part D program, and limit out-of-pocket costs for Medicare beneficiaries; and Medicare negotiation of high-cost drugs facing little or no competition. In order for this legislation to pass, it will require that nearly all Democratic members support a final bill, since no Republicans are likely to support this package.

FDA Grants Full Approval of Pfizer-BioNTech Vaccine On Aug. 23, the U.S. Food and Drug Administration (FDA) granted full approval for the use of the Pfizer-BioNTech COVID-19 vaccine, now marketed as Comirnaty, for the prevention of COVID-19 in individuals 16 and older. The vaccine continues to be available under emergency use authorization (EUA), including for individuals ages 12 through 15 and for a third dose in certain immunocompromised individuals. Data has also been submitted for vaccine use in individuals ages 5 through 11. The FDA is requiring Pfizer to conduct post-marketing studies to further assess the risks of myocarditis and pericarditis following vaccination. In addition, although not required by the FDA, Pfizer has committed to additional post-marketing safety studies, including a pregnancy registry study to evaluate pregnancy and infant outcomes after vaccination during pregnancy.

Medicare will reimburse providers for the booster shot at the same rate that they reimburse for any other coronavirus vaccine dose.

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ATOPIC DERMATITIS | Continued

for any other coronavirus vaccine dose. The national average payment rate for immunization administrators is $40 per coronavirus vaccine dose. The agency promised to share more information about billing and coding for booster shots in the near future.

CMS announced Aug. 13 that immunocompromised individuals will receive the coronavirus booster shot without cost-sharing.

FDA Updates EUAs for COVID-19 Vaccines CMS announced Aug. 13 that immunocompromised individuals will receive the coronavirus booster shot without cost-sharing. This follows the FDA announcement updating the EUA for both the Pfizer-BioNTech and Moderna COVID-19 vaccines, allowing immunocompromised people to receive a third dose of the vaccine at least 28 days following the two-dose regimen to further boost protection. CMS announced that Medicare would cover the administration costs for the coronavirus vaccine booster shots. Medicare will reimburse providers for the booster shot at the same rate that they reimburse 4 | Magellan Rx Report | Fall 2021

President Biden Calls on Congress to Reduce Drug Costs by Allowing Medicare to Negotiate Price of Drugs President Biden spoke from the White House on Aug. 12 to urge Congress to include several provisions in the $3.5 trillion reconciliation bill that passed the U.S. Senate the day before. The president urged Congress to include detailed legislative authority for Medicare to negotiate directly with manufacturers on expensive drugs that face little or no competition. He also called on Congress to limit future price increases to no more than the inflation rate, with any increases above that being returned as a rebate. At the event, he also called for limits to Medicare beneficiary outof-pocket costs and urged that legislation be passed to allow for drug importation from Canada. The reconciliation bill passed by the Senate provides broad spending outlines. The bill must now be passed by the House of Representatives. Following passage in both chambers, the committees of jurisdiction must write detailed tax and spending plans within these guidelines. It is likely that this work, if the House passes the budget bill, will occupy lawmakers through the end of the year. The reconciliation process has no Republican support in either chamber at this point. For legislation to pass, it will require all 50 Democratic senators to support any final package that details tax and spending policies. In the House, the speaker can lose only three Democratic votes if these spending bills are to become law. Government negotiation of drugs is one of many contentious budget issues in the

reconciliation package as Congress begins work on the 2022 legislative budget process.

Chamber of Commerce and PCMA File Lawsuits Challenging Transparency in Coverage Rule The U.S. Chamber of Commerce and the Pharmaceutical Care Management Association (PCMA) filed separate lawsuits Aug. 10 and 12 to challenge the Trump administration’s Transparency in Coverage rule. On Nov. 12, 2020, the departments of HHS, Treasury, and Labor issued a final rule titled “Transparency in Coverage.” The final rule requires issuers to disclose historical net prices for drugs at the National Drug Code level for each applicable plan, beginning in 2022, on machine-readable files. In addition, the rule requires issuers to create an enrollee self-service online tool that would return estimated cost-sharing for covered items and services beginning in 2023 for a select set of services and in 2024 for drugs and all other items and services.

Senate Passes Infrastructure Bill and Budget Reconciliation Package The U.S. Senate passed a $1.2 trillion bipartisan infrastructure bill 69-30 Aug. 10 after weeks of negotiation between Democratic and Republican senators and the White House. The package includes funding for roads, bridges, mass transit, and broadband. It is the largest investment in U.S. infrastructure in decades. To help pay for the bill, the Trump-era rebate rule will be delayed by three years, until 2026, providing savings of approximately $50 billion. The following day, the Senate also passed on a 50-49 partisan vote a $3.5 trillion budget reconciliation package that Democrats have called its investment in families, or American Families Plan.

CMS Revokes Medicaid Work Requirement in Three States On Aug. 10, CMS sent letters to health officials in Ohio, South Carolina, and Utah informing the states that the Biden administration was reversing Trump-era approvals of work requirements for their Medicaid populations. In 2018, the Trump administration issued guidance to let states implement work rules for the first time, arguing that the move would help healthy people find employment. No state had Medicaid work requirements in effect at the beginning of the Biden administration, as the requirements had been halted amid court challenges and the COVID-19 pandemic.

Agencies Release 2021 ACA, CAA Implementation FAQs The departments of Labor, HHS, and Treasury released an 11-page set of frequently asked questions (FAQs) Aug. 10 regarding the implementation of the 2021 ACA and the 2021 Consolidated Appropriations Act (CAA), including provisions of Title I (The No Surprises Act) and Title II (Transparency) of Division BB of the CAA. The guidance also addresses components of the Transparency in Coverage Final Rules, as well as the a gencies’ approach to enforcing the following provisions: • • • • • • • • • • •

Machine-readable files. Price comparison tools. Health plan/issuer ID cards. Good faith estimates. Advanced explanation of benefits (EoBs). Gag clauses. Directories. Balance billing disclosures. Continuity of care. Treatment of grandfathered health plans. Reporting on pharmacy benefits and drug costs.

Notably, the agencies will defer until July 1, 2022, enforcement of the final rules that require health plans and issuers to publish machine-readable files related to prescription drugs while it considers, through notice-and-comment rulemaking, whether the requirement remains appropriate. The agencies intend to propose rulemaking with respect to price comparison tools, ID cards, good faith estimates, advanced EoBs, directories, balance billing, continuity of care, and pharmacy benefits — and, in most cases, are asking for good faith compliance pending rulemaking. Where states are primary enforcers of the applicable provisions, HHS encourages them to take a similar enforcement approach. The agencies make clear that they will not determine that a state is failing to substantially enforce this requirement if it takes this approach.

CMS Proposes to Rescind Medicare Part B Drug Most Favored Nation Model On Aug. 6, CMS released a proposed rule that would rescind the controversial Most Favored Nation (MFN) Model. The MFN Model was announced in November 2020, in the final months of the Trump administration, through an interim final rule with comment (IFC). The model would have tied payment for certain drugs administered under Medicare Part B to international prices. The MFN Model was mandatory and scheduled to run for seven years, beginning in January 2021. Approximately 50 high-spend drugs would have been included. However, shortly after the announcement of the model and release of the IFC, four lawsuits were filed that challenged the legality of the demonstration and the use of an interim final rule instead of the traditional rulemaking pathway. As a result, preliminary injunctions were issued, and the MFN Model did not begin on Jan. 1. The injunction, procedural issues noted by multiple courts, and stakeholder concerns prompted CMS to rescind the November 2020 interim final rule. The agency says that rescinding the rule

addresses the procedural “deficiencies” and allows for time to further consider public comments. CMS indicates that “this action does not reflect any judgement by HHS regarding future policy.” The proposed rule states that HHS is exploring opportunities to promote value-based care and address high Medicare Part B drug costs, manufacturer pricing, and the associated growth in Medicare spending.

The proposed rule states that the U.S. Department of Health and Human Services is exploring opportunities to promote valuebased care and address high Medicare Part B drug costs, manufacturer pricing, and the associated growth in Medicare spending.

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Atopic Dermatitis: Therapeutic Advances and Payer Impact As the AD pipeline picks up speed, payers will consider how to effectively manage the influx of options and correct for discrepancies in access to care. Atopic dermatitis (AD), sometimes called eczema, is the most common chronic inflammatory skin disease and affects around 30% of the U.S. population. Most individuals living with AD are children or adolescents.1 Onset of AD typically occurs by age 5; around 60% of patients develop AD in the first year of life and 90% within the first five years.2, 3 While AD often resolves by the time patients reach adulthood, up to 30% of patients will experience continued symptoms.2, 4

Kathryn Lindhorst Canaday, Pharm.D. VP, Pharmacy Medical Mutual

The primary symptom of AD is an itchy rash. It can develop on any skin area, but it may be more likely to appear in certain places depending on the patient’s age.5 AD can appear as a dry, scaly rash on the cheeks in infants, or as a bumpy rash that can thicken and turn leathery with frequent scratching on necks, wrists, ankles, and in the creases between buttocks and legs, knees, and elbows in children.5 Adults with AD may experience fewer rashes but have extremely dry skin that is easily irritated, hand eczema, or eye problems such as eczema on the eyelids or cataracts.5

Burden of AD Economic Impact AD has profound economic and social impact as well as impact on patient and caregiver quality of life. Costs attributed to AD in the U.S. were estimated at $5.3 billion in 2015.6, 7 Direct medical costs associated with AD can include prescriptions, physician visits, emergency and hospital costs to patients and payers, and over-the-counter pharmacy costs for patients.7 AD can lead to indirect costs from decreased productivity at work, absenteeism, and detriment to quality of life.7

6 | Magellan Rx Report | Fall 2021

Insights from our Medical Pharmacy Experts

WEBCAST: 2020 ELEV ENTH

EDITION

NOW STREAMING magellanrx.com/trendreport

Patient Burden The burden on the patient when living with AD can be substantial; children with AD report itching and scratching, sleep challenges, pain, bleeding, dietary limitations, and emotional and behavioral impact such as irritability and crying.7, 8 There are also reported physical and social functioning issues associated with AD in children, including clothing and bathing restrictions, concerns around outdoor play and swimming, and the stigma around AD that can cause strained social relationships with other children or adults.7, 8 While adults with AD report fewer challenges with social functioning, quality of life in these patients is affected by symptoms and emotional impact.7, 9 Adults with AD reported itching and sleep disturbance as having the most significant impact on quality of life; however, the involvement of visible areas of the body such as the face, as well as genital involvement, also impaired quality of life.7, 9-11

Current Treatment AD is often treated with topical therapies to control itching and repair the skin. The topicals typically used to treat AD are corticosteroids or calcineurin inhibitors, which are mostly available generically.12 Besides these, the most recently approved topical treatment is crisaborole (EUCRISA®), a topical phosphodiesterase-4

enzyme inhibitor that was, at the time of approval, the first new AD treatment in 15 years. Before 2021, there was only one approved biologic for AD, dupilumab (DUPIXENT®). Dupilumab is an injectable biologic, or monoclonal antibody, that inhibits signaling of interleukin-4 and interleukin-13, which play a role in the inflammation associated with AD; the treatment is indicated for patients with moderate to severe AD who are age 6 or older.13 The American Academy of Dermatology and American Academy of Allergy, Asthma, & Immunology guidelines have not been updated since 2014 and 2012, respectively, and thus do not include the newest therapeutic options for AD, crisaborole and dupilumab.14, 15 Light therapy treatment is sometimes used for patients who do not achieve results from topical treatments.12 In some cases, topical or oral antibiotics may be used if the skin rash develops a bacterial infection, which can be common with infants and young children.12 For some patients with AD, especially infants and children, food avoidance may be employed in order to prevent the rash from occurring. Avoidance of skin irritants and extreme temperatures is also a treatment option in some cases.

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ATOPIC DERMATITIS | Continued

Table 1. Atopic Dermatitis Pipeline16 Drug

Manufacturer

Route of Administration

Mechanism of Action

Status

upadacitinib (RINVOQ™)

AbbVie

oral

JAK inhibitor

pending

ruxolitinib phosphate (Jakafi cream)

Incyte

topical

JAK inhibitor

pending

abrocitinib (PF-04965842)

Pfizer

oral

JAK inhibitor

pending

baricitinib (Olumiant)

Eli Lilly and Company; Incyte

oral

JAK inhibitor

pending (phase three)

lebrikizumab

Genentech; Eli Lilly and Company

IL-13 antagonist

phase three

pimecrolimus (IDP-124)

Bausch Health Ortho Dermatologics

topical

macrolide immunosuppressant

phase three

roflumilast (ARQ-151)

Arcutis Biotherapeutics

topical

PDE4 inhibitor

phase three

delgocitinib

LEO Pharma; Japan Tobacco

topical

JAK inhibitor

phase three

tradipitant (VLY-686)

Vanda Pharmaceuticals

oral

NK-1 receptor antagonist

phase three

bermekimab

XBiotech

IV; SQ

IL-1 antagonist

phase two

gusacitinib (ASN002)

Asana BioSciences

oral

JAK inhibitor; Syk inhibitor

phase two

SHR0302

Reistone Biopharma; Jiangsu Hengrui Medicine

oral

JAK inhibitor

phase two

tapinarof

Dermavant Sciences

topical

NSAID

phase two

fevipiprant (QAW039)

Novartis

oral

DP2 (CRTh2) antagonist

phase two

apremilast (Otezla®)

Celgene; Amgen

oral

PDE4 inhibitor

phase two

asimadoline

Tioga Pharmaceuticals

oral

opioid agonist

phase two

KY1005

Kymab

injectable

OX40 ligand inhibitor

phase two

AQX-1125

Aquinox Pharmaceuticals

oral

immunomodulators

phase two

etrasimod

Arena Pharmaceuticals

oral

S1P receptor modulators

phase two

KHK4083

Kyowa Kirin; Amgen

IV; SQ

OX40 ligand inhibitor

phase two

Abbreviations: DP2 (CRTh2) = prostaglandin D2 receptor 2; IL-13 = interleukin 13; IL-1 = interleukin 1; IV = intravenous; JAK = janus kinase; NK-1 = neurokinin-1; PDE4 = phosphodiesterase-4; S1P = sphingosine 1-phosphate; SQ = subcutaneous; Syk = spleen tyrosine kinase

Pipeline The pipeline for AD is expansive and imminent, with multiple new therapies scheduled for approval in 2021. Additional therapies are in phase three and may be approved in 2022. See Table 1 above for an expanded pipeline.

Managed Care Impact The majority of patients with AD are children, and an estimated 50% of children in the U.S. are Medicaid-insured. A significant disparity in AD diagnosis and management has been observed when comparing Medicaid-insured children with children who are commercially insured.17 A 2020 study showed that Medicaid-insured children receive less specialist care, see emergency departments

8 | Magellan Rx Report | Fall 2021

and urgent care centers more often, and have higher rates of asthma and non-atopic comorbidities compared with commercially insured children. High-potency topical corticosteroids and calcineurin inhibitors are prescribed less often and prescriptions for antihistamines are more than three times higher in the Medicaid population.17 This assessment suggests a barrier to access to comparable specialty care for Medicaid-insured children, specifically in the management of AD.17 There is a potential for these disparities to increase as more costly therapies enter the market. The AD space has moved on from its period of slow therapy approvals. With several biologics and other costly therapies likely to launch in the coming few years, payers will divert attention to effectively managing the influx of options in the category. There has

been a high demand for treatment options for this chronic, burdensome condition that impacts a significant population. That demand is likely to translate to demand for newly launched therapies as they become available. Additionally, there may be an increase in patients seeking diagnosis as therapy options expand and awareness of the disease and opportunities for treatment grow. The market growth for AD is projected to increase 130% to $11 billion by 2029.18

new-to-market therapies. Since there is potential for off-label use of dupilumab and newly launched therapies, prior authorization may be key in ensuring appropriate use. Additionally, step therapy may be employed, with low-cost topicals and preferred brands or biologics as required steps. This expansive pipeline carries the promise of a broader AD market, which may lead to more flexibility for payers to negotiate costs and management strategies.

Dupilumab is currently dominant in the AD space, and it may take time for this to adjust as new agents enter the market. Payers will likely strategize to ensure proper use of and access to these

References 1.

“Eczema (Atopic Dermatitis).” National Institute of Allergy and Infectious Diseases, 19 Apr. 2017, https://www.niaid.nih.gov/diseasesconditions/eczema-atopic-dermatitis.

11. Misery, L., et al. “Atopic dermatitis: impact on the quality of life of patients and their partners.” Dermatology, 2007, https://pubmed. ncbi.nlm.nih.gov/17684374/.

Avena-Woods, Carmela. “Overview of Atopic Dermatitis.” AJMC Supplement, 20 June 2017, https://www.ajmc.com/view/overview-ofatopic-dermatitis-article.

12. “Atopic dermatitis (eczema).” Mayo Clinic, https://www.mayoclinic. org/diseases-conditions/atopic-dermatitis-eczema/diagnosistreatment/drc-20353279.

Eichenfield, Lawrence, et al. “Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis.” Journal of the American Academy of Dermatology, 27 Nov. 2013, https://pubmed.ncbi.nlm.nih.gov/24290431/.

13. “FDA approves DUPIXENT® (dupilumab) for moderate-to-severe atopic dermatitis in adolescents.” Regeneron, 11 Mar. 2019, https:// investor.regeneron.com/news-releases/news-release-details/fdaapproves-dupixentr-dupilumab-moderate-severe-atopic.

Ellis, N.C., et al. “Understanding and managing atopic dermatitis in adult patients.” Seminars in Cutaneous Medicine and Surgery, 2012, 31(suppl 3): S18-S22. doi: 10.1016/j.sder.2012.07.006.

14. “Atopic Dermatitis Clinical Guideline.” American Academy of Dermatology Association, 2014, https://www.aad.org/member/ clinical-quality/guidelines/atopic-dermatitis.

“Eczema Types: Atopic Dermatitis Symptoms.” American Academy of Dermatology Association, https://www.aad.org/public/diseases/ eczema/types/atopic-dermatitis/symptoms.

15. “Atopic dermatitis: A practice parameter update 2012.” American Academy of Allergy, Asthma, & Immunology, 2012, https://pubmed. ncbi.nlm.nih.gov/23374261/.

Crawford, Malik, et al. “CPI Detailed Report: Data for September 2015.” U.S. Bureau of Labor Statistics, Sept. 2015, https://fraser. stlouisfed.org/files/docs/publications/cpidr/cpi_201509.pdf.

16. IPD Analytics. “Atopic Dermatitis.”

Drucker, Aaron, et al. “The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Association.” Journal of Investigative Dermatology, Jan. 2017, https://www.sciencedirect.com/science/ article/pii/S0022202X16321200#fn1.

Chamlin, Sarah, et al. “Effects of atopic dermatitis on young American children and their families.” Pediatrics, Sept. 2004, https://pubmed. ncbi.nlm.nih.gov/15342828/.

Holm, E.A., et al. “Life quality assessment among patients with atopic eczema.” British Journal of Dermatology, Apr. 2006, https://pubmed. ncbi.nlm.nih.gov/16536816/.

17. Siegfried, Elaine, et al. “Effects of variations in access to care for children with atopic dermatitis.” BMC Dermatology, 20 Dec. 2020, https://bmcdermatol.biomedcentral.com/articles/10.1186/s12895020-00114-x. 18. Minemyer, Paige. “Optum: Why payers should be watching flurry of drug development activity around eczema.” Fierce Healthcare, 3 May 2021, https://www.fiercehealthcare.com/payer/optum-why-payersshould-be-watching-flurry-drug-development-activity-aroundeczema.

10. Beikert, F.C., et al. “Willingness to pay and quality of life in patients with atopic dermatitis.” Archives of Dermatological Research, Apr. 2014, https://pubmed.ncbi.nlm.nih.gov/23982630/.

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In the treatment of adults with active lupus nephritis…

START WITH A

STRONG

FIRST LINE Indications LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis (LN). Limitations of Use: Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in this situation.

Important Safety Information BOXED WARNINGS: MALIGNANCIES AND SERIOUS INFECTIONS Increased risk for developing malignancies and serious infections with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death. CONTRAINDICATIONS: LUPKYNIS is contraindicated in patients taking strong CYP3A4 inhibitors because of the increased risk of acute and/or chronic nephrotoxicity, and in patients who have had a serious/severe hypersensitivity reaction to LUPKYNIS or its excipients. WARNINGS AND PRECAUTIONS Lymphoma and Other Malignancies: Immunosuppressants, including LUPKYNIS, increase the risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to

increasing doses and duration of immunosuppression rather than to the use of any specific agent. Serious Infections: Immunosuppressants, including LUPKYNIS, increase the risk of developing bacterial, viral, fungal, and protozoal infections (including opportunistic infections), which may lead to serious, including fatal, outcomes. Nephrotoxicity: LUPKYNIS, like other calcineurin inhibitors (CNIs), may cause acute and/or chronic nephrotoxicity. The risk is increased when CNIs are concomitantly administered with drugs associated with nephrotoxicity. Hypertension: Hypertension is a common adverse reaction of LUPKYNIS therapy and may require antihypertensive therapy. Neurotoxicity: LUPKYNIS, like other CNIs, may cause a spectrum of neurotoxicities: severe include posterior reversible encephalopathy syndrome (PRES), delirium, seizure, and coma; others include tremor, paresthesia, headache, and changes in mental status and/or motor and sensory functions. Hyperkalemia: Hyperkalemia, which may be serious and require treatment, has been reported with CNIs, including LUPKYNIS. Concomitant use of agents associated with hyperkalemia may increase the risk for hyperkalemia.

Using LUPKYNIS™ (voclosporin) in combination with MMF and steroids can transform your first-line regimen1,a,b Significantly greater complete renal response rates with LUPKYNIS vs standard of care alone Faster proteinuria reductions than standard of care alone Outcomes achieved with a low-dose steroid regimen Novel CNI with no drug level monitoring required1,2

Complete renal response was achieved in 40.8% of patients with LUPKYNIS and 22.5% with control. Proteinuria reductions (UPCR ≤0.5 mg/mg) were achieved at a median time of 169 days with LUPKYNIS vs 372 days with control.1 b Complete renal response was defined as a confirmed UPCR of ≤0.5 mg/mg; eGFR ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of >20% or no treatment- or disease-related eGFR-associated event at time of assessment; presence of sustained, low-dose steroids (≤10 mg prednisone from Weeks 44-52); and no administration of rescue medications. Proteinuria reduction was based on time to UPCR of ≤0.5 mg/mg.1 CNI=calcineurin inhibitor; eGFR=estimated glomerular filtration rate; MMF=mycophenolate mofetil; standard of care=MMF + steroids; UPCR=urine protein/creatinine ratio. a

See how LUPKYNIS can impact your appropriate patients with lupus nephritis at LUPKYNISpro.com

QTc Prolongation: LUPKYNIS prolongs the QTc interval in a dose-dependent manner when dosed higher than the recommended lupus nephritis therapeutic dose. The use of LUPKYNIS in combination with other drugs that are known to prolong QTc may result in clinically significant QT prolongation. Immunizations: Avoid the use of live attenuated vaccines during treatment with LUPKYNIS. Inactivated vaccines noted to be safe for administration may not be sufficiently immunogenic during treatment with LUPKYNIS. Pure Red Cell Aplasia: Cases of pure red cell aplasia (PRCA) have been reported in patients treated with another CNI immunosuppressant. If PRCA is diagnosed, consider discontinuation of LUPKYNIS. Drug-Drug Interactions: Avoid co-administration of LUPKYNIS and strong CYP3A4 inhibitors or with strong or moderate CYP3A4 inducers. Reduce LUPKYNIS dosage when co-administered with moderate CYP3A4 inhibitors. Reduce dosage of certain P-gp substrates with narrow therapeutic windows when co-administered. ADVERSE REACTIONS The most common adverse reactions (≥3%) were glomerular filtration rate decreased, hypertension, diarrhea, headache, anemia, cough, urinary tract infection,

abdominal pain upper, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite. SPECIFIC POPULATIONS Pregnancy/Lactation: May cause fetal harm. Advise not to breastfeed. Renal Impairment: Not recommended in patients with baseline eGFR ≤45 mL/min/1.73 m2 unless benefit exceeds risk. If used in this population, reduce LUPKYNIS dose. Hepatic Impairment: For mild or moderate hepatic impairment, reduce LUPKYNIS dose. Avoid use with severe hepatic impairment. Please see Brief Summary of Prescribing Information including Boxed Warning on adjacent pages. References: 1. LUPKYNIS [package insert]. Rockville, MD: Aurinia Pharma U.S., Inc., 2021. 2. Kuglstatter A, Mueller F, Kusznir E, et al. Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA247 (voclosporin). Acta Crystallogr D Biol Crystallogr. 2011;67(pt 2):119-123. LUPKYNIS is a trademark of Aurinia Pharmaceuticals Inc. ©2021 Aurinia Pharma U.S., Inc. All Rights Reserved. US-LUP-2100092 06/21

Pure Red Cell Aplasia: Cases of pure red cell aplasia (PRCA) have been reported in patients treated with another CNI immunosuppressant. If PRCA is diagnosed, consider discontinuation of LUPKYNIS. ADVERSE REACTIONS LUPKYNISTM (voclosporin) capsules, BRIEF SUMMARY SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION BOXED WARNINGS: MALIGNANCIES AND SERIOUS INFECTIONS Increased risk for developing malignancies and serious infections with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death. INDICATIONS AND USAGE LUPKYNIS is indicated with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis (LN). Limitations of Use: Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in this situation. CONTRAINDICATIONS LUPKYNIS is contraindicated in patients taking strong CYP3A4 inhibitors because these medications can significantly increase exposure to LUPKYNIS, which may increase the risk of acute and/or chronic nephrotoxicity, and in patients who have had a serious/severe hypersensitivity reaction to LUPKYNIS or its excipients. WARNINGS AND PRECAUTIONS Lymphoma and Other Malignancies: Immunosuppressants, including LUPKYNIS, increase the risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. Serious Infections: Immunosuppressants, including LUPKYNIS, increase the risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections. These infections may lead to serious, including fatal, outcomes. Viral infections reported include cytomegalovirus and herpes zoster infections. Nephrotoxicity: LUPKYNIS, like other calcineurin inhibitors (CNIs), can cause acute and/or chronic nephrotoxicity. The risk is increased when CNIs are concomitantly administered with drugs associated with nephrotoxicity. Consider the risks and benefits of LUPKYNIS treatment in light of the patient’s treatment response and risk of worsening nephrotoxicity, including in the following situations: 1) Longer treatment duration beyond one year. Safety and efficacy of LUPKYNIS have not been established beyond one year. 2) Co-administration with drugs associated with nephrotoxicity. The risk for acute and/or chronic nephrotoxicity is increased when LUPKYNIS is concomitantly administered with drugs associated with nephrotoxicity. Hypertension: Hypertension is a common adverse reaction of LUPKYNIS therapy and may require antihypertensive therapy. Neurotoxicity: Like other CNIs, LUPKYNIS can cause neurotoxicities. The most severe ones include posterior reversible encephalopathy syndrome (PRES), delirium, seizure, and coma; others include tremor, paresthesia, headache, mental status changes, and changes in motor and sensory functions. Hyperkalemia: Hyperkalemia, which may be serious and require treatment, has been reported with CNIs including LUPKYNIS. Concomitant use of agents associated with hyperkalemia may increase the risk for hyperkalemia. QTc Prolongation: LUPKYNIS prolongs the QTc interval in a dosedependent manner after single dose administration at a dose higher than the recommended lupus nephritis therapeutic dose. The use of LUPKYNIS in combination with other drugs that are known to prolong QTc may result in clinically significant QT prolongation. Immunizations: Avoid the use of live attenuated vaccines during treatment with LUPKYNIS. Inactivated vaccines noted to be safe for administration may not be sufficiently immunogenic during treatment with LUPKYNIS.

Clinical Trials Experience A total of 355 patients with LN were treated with voclosporin in the Phase 2 and 3 clinical studies of whom 224 were exposed for at least 48 weeks. A total of 267 patients received at least 1 dose of LUPKYNIS 23.7 mg twice a day with 184 exposed for at least 48 weeks. A total of 88 patients received at least 1 dose of voclosporin 39.5 mg twice a day with 40 exposed for 48 weeks. Patients received background treatment with MMF 2 g daily and an IV bolus of corticosteroids followed by a pre-specified oral corticosteroid taper dosing schedule. Adverse Reactions in ≥3% of Patients Treated with LUPKYNIS 23.7 mg BID and ≥2% Higher than Placebo in Studies 1 and 2 LUPKYNIS 23.7 mg twice a day (n=267)

Placebo (n=266)

Glomerular filtration rate (GFR) decreased*

26%

Hypertension

19%

Diarrhea

19%

13%

Headache

15%

Anemia

12%

Cough

11%

Urinary tract infection

10%

Abdominal pain upper

Dyspepsia

Alopecia

Renal Impairment*

Abdominal Pain

Mouth ulceration

Fatigue

Tremor

Acute kidney injury*

Decreased appetite

Adverse Reaction

*GFR decreased was the most frequently reported renal adverse reaction. Other renal adverse reactions were renal impairment, acute kidney injury, blood creatinine increased, azotemia, renal failure, oliguria, and proteinuria.

Other adverse reactions reported in less than 3% of patients in the LUPKYNIS 23.7 mg group and at a 2% higher rate than in the placebo group through Week 48/52 included gingivitis and hypertrichosis. Studies 1 and 2 were integrated to represent safety through 48/52 weeks for placebo (n=266), LUPKYNIS 23.7 mg twice a day (n=267), and voclosporin 39.5 mg twice a day (n=88). Exposure adjusted incidence rates were adjusted by study for all the adverse events reported in this section. DRUG INTERACTIONS Effect of Other Drugs on LUPKYNIS Strong and Moderate CYP3A4 Inhibitors: Voclosporin is a sensitive CYP3A4 substrate. Co-administration with strong or moderate CYP3A4 inhibitors increases voclosporin exposure, which may increase the risk of LUPKYNIS adverse reactions. Co-administration of LUPKYNIS with strong CYP3A4 inhibitors (e.g., ketoconazole,

itraconazole, clarithromycin) is contraindicated. Reduce LUPKYNIS dosage when co-administered with moderate CYP3A4 inhibitors (e.g., verapamil, fluconazole, diltiazem). Avoid food or drink containing grapefruit when taking LUPKYNIS. Strong and Moderate CYP3A4 Inducers: Voclosporin is a sensitive CYP3A4 substrate. Co-administration with strong or moderate CYP3A4 inducers decreases voclosporin exposure, which may decrease the efficacy of LUPKYNIS. Avoid co-administration of LUPKYNIS with strong or moderate CYP3A4 inducers. Effect of LUPKYNIS on Other Drugs Certain P-gp Substrates Voclosporin is a P-gp inhibitor. Co-administration of voclosporin increases exposure of P-gp substrates, which may increase the risk of adverse reactions of these substrates. For certain P-gp substrates with a narrow therapeutic window, reduce the dosage of the substrate as recommended in its prescribing information, if needed. OATP1B1 Substrates The effect of LUPKYNIS on OATP1B1 substrates (e.g., statins) has not been studied clinically. However, voclosporin is an OATP1B1 inhibitor in vitro, and information suggests an increase in the concentration of these substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when used concomitantly with LUPKYNIS. USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary Avoid use of LUPKYNIS in pregnant women. The available data on the use of LUPKYNIS in pregnant patients are insufficient to determine whether there is a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with systemic lupus erythematosus (SLE). LUPKYNIS may be used in combination with a background immunosuppressive therapy regimen that includes mycophenolate mofetil (MMF). MMF used in pregnant women and men whose female partners are pregnant can cause fetal harm (major birth defects and miscarriage). Refer to the MMF prescribing information for more information on its use during pregnancy. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. Maternal LN increases the risk of hypertension and preeclampsia/eclampsia. Passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block. Lactation There are no available data on the presence of voclosporin in human milk, the effects on the breastfed infant, or the effects on milk production. Voclosporin is present in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Given the serious adverse reactions seen in adult patients treated with LUPKYNIS such as increased risk of serious infections, advise patients that breastfeeding is not recommended during treatment and for at least 7 days after the last dose of LUPKYNIS (approximately 6 elimination half-lives). Females and Males of Reproductive Potential LUPKYNIS may be used in combination with a background immunosuppressive therapy regimen that includes MMF. If LUPKYNIS is administered with MMF, the information for MMF regarding pregnancy testing, contraception, and infertility also applies to this combination regimen. Refer to MMF prescribing information for additional information. Pediatric Use: The safety and efficacy of LUPKYNIS in pediatric patients has not been established.

Geriatric Use: Clinical studies of LUPKYNIS did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Renal Impairment Use of LUPKYNIS is not recommended in patients with a baseline eGFR ≤45 mL/min/1.73 m2 unless the benefit exceeds the risk. If used in patients with severe renal impairment at baseline, LUPKYNIS should be used at a reduced dose. No dosage adjustment is recommended in patients with mild or moderate renal impairment at baseline. Monitor eGFR closely. After initiating therapy, dosing adjustments should be made based on eGFR. Hepatic Impairment Reduce LUPKYNIS dosage in patients with mild/moderate hepatic impairment. Avoid LUPKYNIS in patients with severe hepatic impairment. OVERDOSAGE Symptoms of accidental overdose may include tremor, headache, nausea and vomiting, infections, tachycardia, urticaria, lethargy, and increases in blood urea nitrogen, serum creatinine, and alanine aminotransferase levels. General supportive measures and symptomatic treatment are recommended in cases of overdose. To report SUSPECTED ADVERSE REACTIONS, contact Aurinia Pharma U.S., Inc. at 1‑833‑672‑0028 or FDA at 1‑800‑FDA‑1088 or www.fda.gov/medwatch. This brief summary is based on LUPKYNIS Prescribing Information (FPI-0009) issued January 2021. Additional information can be found at LUPKYNISpro.com.

Lupus and Lupus Nephritis: Advances in Treatment and Management After years of dormancy, the lupus and lupus nephritis pipelines are growing, representing hope for patients and management challenges for payers. Lupus is an autoimmune disease that currently affects about 1.5 million Americans, 90% of whom are women.1 Lupus is more prevalent among women of color, and Black patients with lupus are more likely to experience organ-system involvement.1 The most common form of lupus is systemic lupus erythematosus (SLE), which accounts for approximately 70% of all cases; in half of SLE cases, tissue or major organs such as the heart, lungs, kidneys, or brain will be impacted by the disease.1 The other three forms of lupus are cutaneous lupus, drug-induced lupus, and neonatal lupus. One-third of patients with lupus report having a comorbid autoimmune disorder. Genetics can play a role in the development of lupus; 20% of patients with lupus have a parent or sibling who has developed or will develop lupus.1 Martin Burruano, R.Ph. VP, Pharmacy Services Independent Health

Diagnosis and Complications Diagnosis can be challenging, as many symptoms of SLE can mimic those of a variety of other illnesses. It takes an average of six years for patients with SLE to be correctly diagnosed; 63% of surveyed patients with SLE report being incorrectly diagnosed, and 55% report seeing at least four different healthcare providers prior to receiving an accurate diagnosis.1 While symptoms of SLE can vary widely, some of the most common symptoms include joint pain and swelling, headaches, severe fatigue, a signature rash on the cheeks and nose, hair loss, anemia, blood clots, fever with no cause, and Raynaud’s phenomenon. When SLE affects internal organs, other symptoms can arise, depending on which organ is being impacted.1 In patients with SLE, a type of kidney disease can develop known as lupus nephritis.2 In adults with SLE, 35% to 60% will develop lupus nephritis. Symptoms can include foamy urine, edema, and high blood pressure. Lupus nephritis can be diagnosed through urine tests, blood tests, and a kidney

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Since December 2020, the U.S. Food and Drug Administration has approved two therapies indicated for the treatment of adult patients with active lupus nephritis.

biopsy.2 An estimated 10% to 30% of patients with lupus nephritis will develop kidney failure. In patients with the most severe form of lupus nephritis, called diffuse proliferative glomerulonephritis, permanent scars form on the kidneys, and as scars develop, kidney function declines. Lupus nephritis is associated with other risks, including a higher risk for cancer — specifically B-cell lymphoma — and heart and blood vessel issues.2

Current Treatment Landscape for Lupus Proper treatment for SLE requires management by a rheumatologist or rheumatology team.3, 4 Treatment often varies from patient to patient, and treatment regimens can change depending on the symptoms a patient experiences. Some treatment options include NSAIDs, steroids, immunosuppressive medications, DHEA, and antimalarial drugs such as hydroxychloroquine.3, 4

Anifrolumab (SAPHNELO™)5 In August, the FDA approved anifrolumab (SAPHNELO™, AstraZeneca) for the treatment of moderate to severe lupus in adult patients who are receiving standard therapy. Anifrolumab,

an intravenous monoclonal antibody treatment, is the first-approved type I interferon receptor antagonist and the first new lupus therapy approved in more than a decade. The SAPHNELO clinical development program, which included two phase three TULIP trials and the phase two MUSE trial, demonstrated efficacy and safety; more patients treated with anifrolumab experienced a reduction in overall disease activity across organ systems and achieved sustained reduction in oral corticosteroid use compared to the placebo. Common adverse reactions observed in the clinical trials included nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough.

Current Treatment Landscape for Lupus Nephritis Though lupus nephritis is a common progression of SLE, there was no treatment specifically indicated for it until late 2020. Providers would typically aim to reduce inflammation in the kidneys and decrease overall immune system activity.2 The treatments used were not effective in preventing new flares or inducing remission.6 Since December 2020, the U.S. Food and Drug Administration (FDA) has approved two therapies indicated for the treatment of adult patients with active lupus nephritis.

Voclosporin (LUPKYNIS™)7, 8 In January 2021, the FDA approved voclosporin (LUPKYNIS™, Aurinia Pharmaceuticals) in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis. Voclosporin is a calcineurin inhibitor and the first and only FDA-approved oral therapy for

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LUPUS AND LUPUS NEPHRITIS | Continued

Table 1. Lupus and Lupus Nephritis Pipeline9 Drug

Manufacturer

Route of Administration

Mechanism of Action

Status

Systemic Lupus Erythematosus (SLE) anifrolumab (MEDI546 SQ)

MedImmune; AstraZeneca

type I interferon inhibitor

phase three

rigerimod (Lupuzor™)

ImmuPharma

immunomodulator

phase three

dapirolizumab pegol

Biogen; UCB

injectable

CD40L inhibitor

phase three

BIIB059

Biogen

BDCA2 antibody

phase three

baricitinib (Olumiant)

Eli Lilly and Company; Incyte

oral

JAK inhibitor

phase three

obinutuzumab (GAZYVA™)

Roche; Genentech

anti-CD20 antibody

phase three

secukinumab (COSENTYX® SC)

Novartis

IL-17 antagonist

phase three

ravulizumab-cwvz (ULTOMIRIS®)

Alexion

complement inhibitors

phase two

Lupus Nephritis

Abbreviations: BDCA2 = anti-blood dendritic cell antigen 2; IL-17 = interleukin 17; IV = intravenous; JAK = Janus kinase; SQ = subcutaneous

lupus nephritis. The phase three AURORA trial and phase two AURA-LV trial were used to assess efficacy. In the trials, 533 adult patients with biopsy-confirmed lupus nephritis were randomized to receive either voclosporin or a placebo alongside their standard therapy, with both groups of patients receiving concurrent mycophenolate mofetil. After 12 months, voclosporin with standard therapy was more than two times as effective as standard therapy alone at achieving complete renal response. The group receiving voclosporin experienced 50% reduction in urine protein creatinine ratio twice as fast as the placebo group, and a higher proportion achieved complete renal response at 24 weeks compared to the placebo group. Side effects associated with voclosporin included decreased glomerular filtration rate, hypertension, diarrhea, headache, anemia, urinary tract infection, upper abdominal pain, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulcers, fatigue, tremor, acute kidney injury, and decreased appetite.

16 | Magellan Rx Report | Fall 2021

Belimumab (BENLYSTA)10 The FDA approved belimumab (BENLYSTA, GlaxoSmithKline) in December 2020 as the first treatment for adults with lupus nephritis. Belimumab is an intravenous infusion monoclonal antibody. Results from the BLISS-LN study, which involved 448 patients randomized to receive either belimumab or a placebo plus standard therapy, supported efficacy. A significantly greater number of patients receiving belimumab achieved primary efficacy renal response at two years compared to the placebo group. The group receiving belimumab had a higher rate of achieving major secondary endpoints, including complete renal response and time to renal-related event or death, compared to the placebo group. Adverse reactions associated with belimumab included fatal infections, nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, extremity pain, depression, migraine, pharyngitis, cystitis, leukopenia, and viral gastroenteritis.

In January 2021, the FDA approved voclosporin (LUPKYNIS™, Aurinia Pharmaceuticals) in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis. Cost Assessment In a cost-utility analysis, voclosporin in combination with standard care for lupus nephritis demonstrated acceptable costeffectiveness in comparison to standard care alone, and voclosporin demonstrated more health benefits at a lower cost when compared with the one other FDA-indicated treatment for lupus nephritis. The Institute for Clinical and Economic Review (ICER) assessed the comparative clinical effectiveness and value of both voclosporin and belimumab for the treatment of lupus nephritis.11 ICER reported that while there is substantial uncertainty regarding longterm use and outcomes, the drugs both appear to be priced within the recommended health-benefit price benchmark ranges. The final policy recommendation from ICER noted that payers should design coverage criteria that do not narrow coverage from the FDA label.1 ICER has not yet reviewed anifrolumab.

Payer Management After a slow period regarding new therapies in this space, the category is seeing an influx of new approved and pipeline therapies for SLE and lupus nephritis. With growing competition in the lupus nephritis category, where there were previously no FDA-approved therapies, payers should anticipate an increase in associated

costs. Strategic policy development will be crucial to managing costs and ensuring appropriate access to treatment. Considering the high cost of these therapies and this specialty disease state, prior authorization may be a key tool for ensuring that patients meet clinical criteria and for managing costs. Voclopsorin and belimumab have different routes of administration — which may be a consideration in terms of policy development — and sites of care, as belimumab is administered intravenously. Considering the additional agents in the pipeline for lupus nephritis, guidelines recommending place in therapy for these new options may be a valuable resource for payers in supporting policy development or prior authorization criteria. The promising SLE and lupus nephritis pipeline presents exciting new options for this patient population to improve outcomes, but it will require thoughtful strategizing by payers to ensure effective management.

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LUPUS AND LUPUS NEPHRITIS | Continued

MRx PIPELINE

Our latest quarterly report on anticipated specialty and traditional drugs in the pipeline

A VIEW INTO UPCOMING SPECIALTY & TRADITIONAL DRUGS JULY 2021

magellanrx.com/pipeline

References 1.

“Lupus facts and statistics.” Lupus Foundation of America, 6 Oct. 2016, https://www.lupus.org/resources/lupus-facts-and-statistics.

“Lupus and Kidney Disease (Lupus Nephritis).” National Institute of Diabetes and Digestive and Kidney Diseases, Jan. 2017, https://www. niddk.nih.gov/health-information/kidney-disease/lupus-nephritis.

“Medications used to treat lupus.” Lupus Foundation of America, 4 Aug. 2021, https://www.lupus.org/resources/medications-used-totreat-lupus.

“Lupus Medications and Treatment Options.” Johns Hopkins Lupus Center, https://www.hopkinslupus.org/lupus-treatment/lupusmedications/.

“Saphnelo (anifrolumab) approved in the US for moderate to severe systemic lupus erythematosus.” AstraZeneca, 2 Aug. 2021, https:// www.astrazeneca.com/media-centre/press-releases/2021/saphneloapproved-in-the-us-for-sle.html.

Parodis, Ioannis, et al. “Prediction of prognosis and renal outcome in lupus nephritis.” Lupus Science & Medicine, 18 Feb. 2020, https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC7046967/.

18 | Magellan Rx Report | Fall 2021

“FDA Approves Aurinia Pharmaceuticals’ LUPKYNIS™ (voclosporin) for Adult Patients with Active Lupus Nephritis.” Aurinia, 22 Jan. 2021, https://ir.auriniapharma.com/press-releases/detail/210/fdaapproves-aurinia-pharmaceuticals-lupkynis.

Laday, Jason. “FDA approves Lupkynis, first-ever oral therapy for lupus nephritis.” Healio News, 22 Jan. 2021, https://www.healio.com/ news/rheumatology/20210123/fda-approves-lupkynis-firsteveroral-therapy-for-lupus-nephritis.

IPD Analytics. “Lupus Nephritis.”

10. “FDA approves GSK’s BENLYSTA as the first medicine for adult patients with active lupus nephritis in the US.” GlaxoSmithKline, 17 Dec. 2020, https://www.gsk.com/en-gb/media/press-releases/fdaapproves-gsk-s-benlysta-as-the-first-medicine-for-adult-patientswith-active-lupus-nephritis-in-the-us/. 11. “Belimumab and Voclosporin for Lupus Nephritis; Final Policy Recommendations.” Institute for Clinical and Economic Review, 16 Apr. 2021, https://icer.org/wp-content/uploads/2020/11/ICER_LupusNephritis_Policy-Recommendations_041621.pdf.

Biosimilar Update and Pipeline In the seven years since the first biosimilar approval in the U.S., biosimilars have established a presence in the healthcare market. They continue to be a point of interest for all healthcare stakeholders, as there is continued activity and advancement in the space. In July 2021, the U.S. Food and Drug Administration (FDA) approved

the first interchangeable biosimilar insulin product for diabetes, marking a milestone with several other insulin biosimilars in the pipeline.1 Below, we outline a few recent approvals in the space, as well as biosimilars under FDA review and in phase three trials.

Table 1. Recent Approvals2 Name

Manufacturer

Clinical Use

Dosage Form

Approval Date

RIABNI™ (rituximab-arrx)

Amgen

NSCLC; CLL; GPA; MPA

December 2020

NYVEPRIA™ (pegfilgrastim-apgf)

Pfizer

neutropenia/leukopenia

June 2020

Hulio (adalimumab-fkjp)

Viatris

RA; AS; PSO; PsA; JIA; CD; UC

July 2020

semglee® (insulin glargine-yfgn)

Viatris

T1DM; T2DM

July 2021

Abbreviations: AS = ankylosing spondylitis; CD = Crohn’s disease; CLL = chronic lymphocytic leukemia; GPA = granulomatosis with polyangiitis; IV = intravenous; JIA = juvenile idiopathic arthritis; MPA = microscopic polyangiitis; NSCLC = non-small cell lung cancer; PsA = psoriatic arthritis; PSO = psoriasis; RA = rheumatoid arthritis; SQ = subcutaneous; T1DM = Type 1 diabetes mellitus; T2DM = Type 2 diabetes mellitus; UC = ulcerative colitis

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BIOSIMILAR UPDATE AND PIPELINE | Continued

Table 2. Biosimilars Currently Under FDA Review Name

Manufacturer

Clinical Use

Dosage Form

Approval Status

FDA Approval

adalimumab (biosimilar to AbbVie’s HUMIRA®)

Alvotech

RA; AS; PSO; PsA; JIA; CD; UC

submitted — BLA

September 2021

ranibizumab (biosimilar to Genentech’s Lucentis®)

Samsung

wet AMD

intravitreal

submitted — BLA

SeptemberOctober 2021

bevacizumab (biosimilar to Genentech’s Avastin®)

Bio-Thera Solutions

brain cancer; cervical cancer; CRC; NSCLC; ovarian cancer; RCC

submitted — BLA

11/27/2021

adalimumab (biosimilar to AbbVie’s HUMIRA®)

Coherus BioSciences

RA; AS; PSO; PsA; JIA; CD; UC

submitted — BLA

December 2021

pegfilgrastim (biosimilar to Amgen’s Neulasta®)

Lupin

neutropenia/leukopenia

submitted — BLA

April 2022

bevacizumab (biosimilar to Genentech’s Avastin®)

Amneal Pharmaceuticals

brain cancer; cervical cancer; CRC; NSCLC; ovarian cancer; RCC

submitted — BLA

April-May 2022

bevacizumab (biosimilar to Genentech’s Avastin®)

Centus BiotherapeuticsAstraZeneca

brain cancer; cervical cancer; CRC; NSCLC; ovarian cancer; RCC

submitted — BLA

pending

bevacizumab (biosimilar to Genentech’s Avastin®)

Samsung BioepisMerck

brain cancer; cervical cancer; CRC; NSCLC; ovarian cancer; RCC

submitted — BLA

pending

bevacizumab (biosimilar to Genentech’s Avastin®)

Viatris-Biocon

brain cancer; cervical cancer; CRC; NSCLC; ovarian cancer; RCC

submitted — BLA

pending

filgrastim (biosimilar to Amgen’s NEUPOGEN®)

Amneal Pharmaceuticals

neutropenia/leukopenia

IV, SQ

submitted — BLA

pending

filgrastim (biosimilar to Amgen’s NEUPOGEN®)

Apotex

neutropenia/leukopenia

submitted — BLA

pending

filgrastim (biosimilar to Amgen’s NEUPOGEN®)

Tanvex BioPharma

neutropenia/leukopenia

submitted — BLA

pending

insulin aspart (biosimilar to Novo Nordisk’s NovoLog®)

Viatris (Mylan)

T1DM; T2DM

submitted — BLA

pending

pegfilgrastim (biosimilar to Amgen’s Neulasta®)

Amneal Pharmaceuticals

neutropenia/leukopenia

submitted — BLA

pending

pegfilgrastim (biosimilar to Amgen’s Neulasta®)

Apotex

neutropenia/leukopenia

submitted — BLA

pending

pegfilgrastim (biosimilar to Amgen’s Neulasta®)

Fresenius

neutropenia/leukopenia

submitted — BLA

pending

Abbreviations: AMD = age-related macular degeneration; AS = ankylosing spondylitis; CD = Crohn’s disease; CRC = colorectal cancer; JIA = juvenile idiopathic arthritis; IV = intravenous; NSCLC = nonsmall cell lung cancer; PsA = psoriatic arthritis; PSO = psoriasis; RA = rheumatoid arthritis; RCC = renal cell carcinoma; SQ = subcutaneous; T1DM = Type 1 diabetes mellitus; T2DM = Type 2 diabetes mellitus; UC = ulcerative colitis

Table 3. Current Phase Three Biosimilar Studies Name

Manufacturer

Clinical Use

Dosage Form

Status

adalimumab (biosimilar to AbbVie’s HUMIRA )

Fresenius

RA; AS; PSO; PsA; JIA; CD; UC

phase three

adalimumab (biosimilar to AbbVie’s HUMIRA®)

Viatris (Mylan)

RA; AS; PSO; PsA; JIA; CD; UC

phase three

aflibercept (biosimilar to Regeneron’s EYLEA )

Santo; Formycon

diabetic macular edema; wet AMD

intravitreal

phase three

aflibercept (biosimilar to Regeneron’s EYLEA®)

Viatris (Mylan); Janssen

diabetic macular edema; wet AMD

intravitreal

phase three

aflibercept (biosimilar to Regeneron’s EYLEA®)

Samsung BioepisBiogen

diabetic macular edema; wet AMD

intravitreal

phase three

denosumab (biosimilar to Amgen’s Prolia®)

Novartis

osteoporosis/osteopenia

phase three

20 | Magellan Rx Report | Fall 2021

Table 3. Current Phase Three Biosimilar Studies (Continued) Name

Manufacturer

Clinical Use

Dosage Form

Status

eculizumab (biosimilar to Alexion’s SOLIRIS )

Amgen

paroxysmal nocturnal hemoglobinuria

phase three

etanercept (biosimilar to Amgen’s ENBREL®)

Coherus BioSciences

RA; polyarticular JIA; AS; PSO; PsA

phase three

follitropin alfa (biosimilar to EMD Serono’s Gonal-f®)

Finox AG

female reproductive disorder

phase three

follitropin alfa (biosimilar to EMD Seron’s Gonal-f®)

Allergan

female reproductive disorder

phase three

infliximab (biosimilar to Janssen’s REMICADE®)

Nichi-Iko

RA; AS; PSO; PsA; CD; UC

phase three

insulin aspart (biosimilar to Novo Nordisk’s NovoLog®)

Sanofi

T1DM; T2DM

phase three

insulin glargine (biosimilar to Sanofi’s Lantus®)

Gan & Lee-Sandoz

T1DM; T2DM

phase three

natalizumab (biosimilar to Biogen’s TYSABRI )

Novartis

phase three

ranibizumab (biosimilar to Genentech’s Lucentis®)

STADA ArzneimittelBausch Health

wet AMD

intravitreal

phase three

ranibizumab (biosimilar to Genentech’s Lucentis®)

Coherus BioSciences

wet AMD

intravitreal

phase three

rituximab (biosimilar to Genentech’s RITUXAN®)

Amgen

RA; CLL/SLL; NHL (indolent); ANCAassociated vasculitis

phase three

rituximab (biosimilar to Genentech’s RITUXAN®)

Archigen Biotech

RA; CLL/SLL; NHL (indolent); ANCAassociated vasculitis

phase three

tocilizumab (biosimilar to Genentech’s ACTEMRA®)

Bio-Thera Solutions

phase three

trastuzumab (biosimilar to Genentech’s Herceptin®)

Novartis

breast cancer; gastric/ gastroesophageal cancer

phase three

trastuzumab (biosimilar to Genentech’s Herceptin®)

Tanvex BioPharma

breast cancer; gastric/ gastroesophageal cancer

phase three

ustekinumab (biosimilar to Janssen’s STELARA®)

Formycon

PSO

IV; SQ

phase three

ustekinumab (biosimilar to Janssen’s STELARA®)

Amgen

PSO

IV; SQ

phase three

ustekinumab (biosimilar to Janssen’s STELARA®)

Intas

PSO

IV; SQ

phase three

Abbreviations: AMD = age-related macular degeneration; ANCA = antineutrophil cytoplasmic antibodies; AS = ankylosing spondylitis; CD = Crohn’s disease; CLL = chronic lymphocytic leukemia; JIA = juvenile idiopathic arthritis; IV = intravenous; MS = multiple sclerosis; NHL = non-Hodgkin lymphoma; PsA = psoriatic arthritis; PSO = psoriasis; RA = rheumatoid arthritis; SLL = small lymphocytic lymphoma; SQ = subcutaneous; T1DM = Type 1 diabetes mellitus; T2DM = Type 2 diabetes mellitus; UC = ulcerative colitis

References 1.

“FDA Approves First Interchangeable Biosimilar Insulin Product for Treatment of Diabetes.” U.S. Food and Drug Administration, 28 July 2021, https://www.fda.gov/news-events/press-announcements/fdaapproves-first-interchangeable-biosimilar-insulin-product-treatmentdiabetes.

“Biosimilar Product Information.” U.S. Food and Drug Administration, 29 July 2021, https://www.fda.gov/drugs/biosimilars/biosimilarproduct-information.

Visit us online at magellanrx.com/mrxreport | 21

Takeda is a global, R&D-driven biopharmaceutical company committed to discovering and delivering life-changing treatments and vaccines that have a lasting impact on society. Since our founding in 1781 in a market stall in Osaka, Japan, our values endure by putting patient needs first, building trust with society, strengthening our reputation, and developing the business - in that order.

Alzheimer’s Disease: Treatment Update and Managed Care Implications As the number of people living with Alzheimer’s disease increases, collaboration between payers and manufacturers will be key in managing costs, ensuring access, and improving outcomes for patients. About 6.2 million Americans over age 65 live with Alzheimer’s disease; 72% are age 75 or older and nearly two-thirds are women. As the population of Americans over age 65 increases, the number of those living with Alzheimer’s will grow proportionately, reaching 12.7 million by 2050.1 According to a 2018 report, total costs of care associated with Alzheimer’s disease are estimated at $277 billion and anticipated to pass $1 trillion by 2050.2

Andrew J. Colby, R.Ph., MBA Senior Director, Clinical Operations Health New England

The complex progression of Alzheimer’s disease continues to be researched; it is likely that a significant symptom-free period occurs in which damage is occurring in the brain but the person remains untreated and undiagnosed because there are no symptoms presenting.3 Most patients have late-onset Alzheimer’s, meaning symptoms first appear in their mid-60s, while the less common early-onset Alzheimer’s causes symptoms to appear between a person’s 30s and mid-60s. Usually, the first symptoms to appear will be memory problems, but other early-stage symptoms can include other signs of cognitive impairment, such as difficulty finding words, vision or spatial issues, and impaired reasoning or judgment. Patients will experience increasing cognitive difficulties as Alzheimer’s progresses through the several stages — preclinical, mild, moderate, and severe.3 Symptoms associated with each stage can be found in Table 1.

Current Treatment Landscape Due to the complex nature of Alzheimer’s, it is typically treated with multiple modalities or therapies to improve outcomes.4 While several treatments have been approved by the U.S. Food and Drug Administration (FDA) to help manage Alzheimer’s symptoms, most of these treatments are most beneficial for patients in early or middle stages of disease progression.4 Cholinesterase inhibitors such as

24 | Magellan Rx Report | Fall 2021

Table 1. Alzheimer’s Symptoms by Disease Stage3 Disease Stage: Mild Memory loss Poor judgment leading to bad decisions Loss of spontaneity and sense of initiative Taking longer to complete normal daily tasks Repeating questions Trouble handling money and paying bills Wandering and getting lost Losing things or misplacing them in odd places Mood and personality changes Increased anxiety and/or aggression

Disease Stage: Moderate Increased memory loss and confusion Inability to learn new things Difficulty with language and problems with reading, writing, and working with numbers Difficulty organizing thoughts and thinking logically Shortened attention span Problems coping with new situations Difficulty carrying out multistep tasks, such as getting dressed Problems recognizing family and friends Hallucinations, delusions, and paranoia Impulsive behavior, such as undressing at inappropriate times or places or using vulgar language Inappropriate outbursts of anger

Moderate to severe Alzheimer’s is often treated with memantine, an N-methyl D-aspartate antagonist, which can decrease symptoms, potentially enabling some patients to maintain daily functions longer than they would without this treatment. Other FDA-approved drugs include donepezil, rivastigmine, and a combination therapy of memantine and donepezil.4 Since Alzheimer’s is often associated with a variety of behavioral symptoms, attempts to manage these symptoms with behavioral health interventions are encouraged prior to the use of pharmacotherapy for symptom management.4

Aducanumab (ADUHELM®) In June, the FDA approved aducanumab (ADUHELM®, Biogen) for the treatment of Alzheimer’s via the accelerated approval pathway.5 Aducanumab is a monoclonal antibody administered as a once-monthly intravenous infusion; it is the first new treatment indicated for Alzheimer’s in 17 years and the first therapy that targets the fundamental pathophysiology of the disease.5 Efficacy was evaluated in two phase three clinical trials. One trial met the primary endpoint showing primary reduction in clinical decline, while the second trial did not meet the primary endpoint. In the former trial, patients treated with aducanumab had significant dose- and time-dependent reduction of amyloid beta plaque, while control patients had no reduction. There is a warning of amyloidrelated imaging abnormalities associated with aducanumab treatment, as well as hypersensitivity reactions, headache, falls, diarrhea, confusion, delirium, and disorientation.

Restlessness, agitation, anxiety, tearfulness, and wandering Repetitive statements or movement; occasional muscle twitches

Disease Stage: Severe Inability to communicate Weight loss Seizures Skin infections Difficulty swallowing Groaning, moaning, or grunting Increased sleeping Loss of bowel or bladder control

galantamine, rivastigmine, and donepezil are commonly prescribed for mild to moderate Alzheimer’s symptoms as they can provide some reduction or management of cognitive and behavioral symptoms.4

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ALZHEIMER’S | Continued

Table 1. Alzheimer’s Disease Pipeline6 Drug

Manufacturer

Route of Administration

Mechanism of Action

Status

donepezil (Adlarity)

Corium

acetylcholinesterase inhibitor

pending

lumateperone tosylate (CAPLYTA®)

Intra-Cellular Therapies

oral

atypical antipsychotic

pending (12/17/2021)

gantenerumab

Genentech; Roche

amyloid-β protein inhibitor

phase three

lecanemab (BAN2401)

Biogen; Eisai

amyloid-β protein inhibitor

phase three

semaglutide (RYBELSUS®)

Novo Nordisk; Emisphere Technologies

oral

glucagon-like peptide-1 agonist

phase three

ALZ-801

Alzheon

oral

amyloid-β protein inhibitor

phase three phase three

methylthioninium (LMTX™)

TauRx Pharmaceuticals

oral

second-generation tau protein aggregation inhibitor

masitinib

AB Science

oral

receptor TKI

phase three phase three

bupropion + dextromethorphan (AXS-05)

Axsome Therapeutics

oral

NDRI

COR388

Cortexyme

oral

Kgp inhibitor

phase three

cromolyn + ibuprofen (ALZT-OP1)

AZTherapies

inhalation

NSAIDs

phase three

sodium oligomannate (GV-971)

Shanghai Green Valley

oral

microbiome therapy

phase three

NE3107

Neurmedix

oral

anti-inflammatory agent

phase three

donanemab

Eli Lilly and Company

TBD

phase two

tilavonemab (ABBV-8E12)

AbbVie

anti-tau antibody

phase two

xanamem

Actinogen Medical

oral

11beta-hydroxysteroid dehydrogenase type 1

phase two (developing)

canakinumab (ILARIS®)

Novartis

IL-1 antagonist

phase two

LSD1 inhibitor

phase two (developing)

vafidemstat (ORY-2001)

Oryzon Genomics

oral

Abbreviations: IL-1 = interleukin-1; IV = intravenous; Kgp = gingipain K; LSD1 = lysine-specific demethylase 1; NDRI = norephinephrine-dopamine reuptake inhibitor; NSAIDs = nonsteroidal antiinflammatory drugs; SQ = subcutaneous; TD = transdermal; TKI = tyrosine kinase inhibitor

As aducanumab was approved via an accelerated approval pathway, Biogen must conduct a new randomized, controlled clinical trial to verify its clinical benefit.5 Following the approval of aducanumab, the FDA released a statement explaining the data from the trial and the decision to grant accelerated approval, as well as residual uncertainties.7 Notably, the Peripheral and Central Nervous System Drugs Advisory Committee did not find it reasonable to consider clinical benefit of the one successful trial as primary evidence supporting approval, but the Committee did not discuss the option of accelerated approval. Results from the trial showed that aducanumab was associated with a greater reduction in amyloid beta plaques than the placebo (-0.238 vs. -0.005, respectively); thus, the FDA concluded that this reduction in plaques is reasonably likely to result in clinical benefit and justified accelerated approval, pending results from a new confirmatory trial.7 The Institute for Clinical and Economic Review issued an evidence report finding the price range needed to reach standard

26 | Magellan Rx Report | Fall 2021

cost effectiveness for aducanumab is $3,000 to $8,400; this is an 85% to 95% discount from the announced list price.8 A public meeting was held in July with a roundtable of stakeholders to discuss the mismatch between the announced price and valuebased estimates, as well as coverage options and potential designs for the required confirmatory trial.8

Impact on Payers With the approval of aducanumab, health policy experts are calling for the U.S. Centers for Medicare & Medicaid Services (CMS) to issue a national coverage determination (NCD) to avoid any confusion over coverage for the treatment.9 Since a significant proportion of the Medicare population could benefit from Alzheimer’s treatment, an NCD could potentially provide a clear, evidence-based policy to protect those patients, ensure access where appropriate, and avoid conflicting policies upon launch.9 CMS may be waiting to coordinate with the FDA on data collected in the required post-approval trials in order to issue an NCD policy. In an absence of any NCD, a

number of plans have made the decision not to cover aducanumab at this point in time, citing lack of evidence of the treatment. Several payers and hospital systems have decided not to initiate use of aducanumab until alternative reimbursement mechanisms are explored. Additionally, questions about aducanumab’s approval have arisen within the FDA and among members of U.S. Congress. This will likely only lead to more hesitation around uptake of the drug. Considering an anticipated 80% to 90% of the population using aducanumab are expected to be Medicare beneficiaries, the outof-pocket cost for patients may be significant, as this population is not eligible for many copay assistance programs. Payers will have to effectively develop criteria and strategize to ensure that patients receiving aducanumab will clinically benefit from therapy. Subsequent approvals and multiple novel therapies on the market will require strategic management and policymaking by CMS, as analysts suggest that 96% of the market for these treatments are in the Medicare population. With the accelerated approval of aducanumab, the approval of other pipeline drugs may follow. Cost effectiveness of new Alzheimer’s treatments is an important starting point for setting value-based prices; performance warranties helping to apportion risk associated with initial treatment can be an important negotiation point for payers and manufacturers.10 As seen in other disease states with innovative therapies, subscription payment plans may be a useful tool to address

With the approval of aducanumab, health policy experts are calling for the U.S. Centers for Medicare & Medicaid Services to issue a national coverage determination to avoid any confusion over coverage for the treatment. affordability as novel Alzheimer’s therapies enter the market.10 Different value-based agreements may be a solution for a variety of costly treatment options in the Alzheimer’s space, but they would require efficient care models for screening and treatment in order to be effective.11 Collaboration between payers and manufacturers will be key in managing costs, ensuring access, and improving outcomes for Alzheimer’s patients.11

CLINICAL

ALERT READ NOW

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ALZHEIMER’S | Continued

References 1.

“Facts and Figures.” Alzheimer’s Association, 2021, https://www.alz. org/alzheimers-dementia/facts-figures.

“Costs Associated With Alzheimer’s Disease Reach $277 Billion Annually, Report Finds.” Administration for Community Living, 20 Mar. 2018, https://acl.gov/news-and-events/news/costs-associatedalzheimers-disease-reach-277-billion-annually-report-finds.

“What Are the Signs of Alzheimer’s Disease?” National Institute on Aging, 16 May 2017, https://www.nia.nih.gov/health/what-are-signsalzheimers-disease.

“How Is Alzheimer’s Disease Treated?” National Institute on Aging, 8 July 2021, https://www.nia.nih.gov/health/how-alzheimers-diseasetreated.

“FDA Grants Accelerated Approval for Alzheimer’s Drug.” U.S. Food and Drug Administration, 7 June 2021, https://www.fda.gov/newsevents/press-announcements/fda-grants-accelerated-approvalalzheimers-drug.

IPD Analytics. “Alzheimer’s disease.”

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“FDA’s Decision to Approve New Treatment for Alzheimer’s Disease.” U.S. Food and Drug Administration, 7 June 2021, https://www.fda. gov/drugs/news-events-human-drugs/fdas-decision-approve-newtreatment-alzheimers-disease.

“Alzheimer’s Disease: An assessment on aducanumab.” Institute for Clinical and Economic Review, July 2021, https://icer.org/assessment/ alzheimers-disease-2021/.

Minemyer, Paige. “Experts: CMS should act quickly on a national coverage decision for Biogen’s newly approved Alzheimer’s drug.” Fierce Healthcare, 7 June 2021, https://www.fiercehealthcare.com/ payer/experts-cms-should-act-quickly-a-national-coverage-decisionfor-biogen-s-newly-approved.

10. Lin, Pei-Jung, et al. “Preparing the health-care system to pay for new Alzheimer’s drugs.” Alzheimers Dement, Nov. 2020, https://pubmed. ncbi.nlm.nih.gov/32808733/. 11. Hung, Anna, et al. “Addressing Challenges in Payment and Access to Treatments for Early-Stage Alzheimer’s Disease.” Duke Margolis Center for Health Policy, 2020, https://healthpolicy.duke.edu/sites/ default/files/2020-03/duke_alzheimerissuebrief-2020.pdf.

Chronic Kidney Disease: Emerging Therapies and Management Strategies As the CKD burden increases with disease progression, prevention and slowing of the disease are key to managing costs for a growing population of patients. Chronic kidney disease (CKD) occurs in patients whose kidneys have become damaged and do not function as well over time. More than 15% of adults in the U.S. — 37 million people — live with CKD.1 With an estimated 9 in 10 adults with CKD unaware of their condition, the disease remains largely underdiagnosed. CKD is more common in adults over the age of 65 (representing 38%) compared to those ages 45-64 (12%) and 18-44 (6%).1 The most recent data estimate that Medicare costs for CKD totaled more than $81.8 billion in 2018.1 CKD costs are often driven by inpatient admissions, which increase with each progressive stage of CKD, as well as readmissions.2

Stacy Inman, Pharm.D. Senior Clinical Project Manager Magellan Method

Type 2 diabetes is the leading cause of CKD and kidney failure in the U.S. Prevention and slowing progression of CKD can be accomplished through successful management of major risk factors, including high blood pressure and high blood sugar levels.3 Since the condition worsens over time and related health problems commonly occur, prevention of CKD is crucial. CKD increases the risk for heart disease and stroke;4 thus, continued management of high blood pressure, blood sugar, and cholesterol levels is important for improved outcomes. Additional health issues associated with CKD are anemia and low red blood cell count; excess fluid causing high blood pressure, swelling in the legs, or shortness of breath; weakened immune system; loss of appetite or nausea; decreased sexual response; confusion, problems with memory and thinking, or depression; low calcium levels; and high phosphorus and potassium levels in the blood.4 Another complication from CKD is CKD-associated pruritus, or chronic itching, which occurs in 20% of CKD cases and 40% of end-stage renal disease cases.5 It is commonly attributed to toxin buildup, peripheral neuropathy, immune system dysregulation, or opioid dysregulation.5 As CKD progresses, damage and loss of function can become severe enough to cause kidney failure, at which point dialysis or kidney transplant is necessary for survival.4 Progression to kidney failure, especially in older adults, is more likely if the kidneys are damaged due to poor

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CHRONIC KIDNEY DISEASE | Continued

With the growing number of older Americans, the number of people living with CKD will continue to increase, making CKD management a priority for strategic management.

management of CKD risk factors. Early detection and proper treatment of CKD can lead to better outcomes and potentially prevent kidney failure.4

Current Treatment Landscape Treatment for CKD is based on the stage of the disease. Most commonly, a comprehensive treatment plan will include lifestyle modifications and drug therapy to manage associated health issues such as high blood pressure and cholesterol — and, for patients that progress to end-stage renal disease, dialysis and kidney transplant.

Finerenone (KERENDIA®)6 The FDA approved finerenone (KERENDIA®, Bayer) in July 2021 for reduction of risk of kidney function decline, kidney failure, cardiovascular death, nonfatal heart attacks, and hospitalization for heart failure in adults with CKD associated with Type 2 diabetes. Finerenone is an oral nonsteroidal selective mineralocorticoid receptor antagonist (MRA); it is the first MRA and third FDA-approved treatment for CKD in Type 2 diabetes. A randomized, multicenter, double-blind, placebo-controlled study of 5,674 patients with CKD associated with Type 2

30 | Magellan Rx Report | Fall 2021

diabetes was conducted to evaluate the efficacy of finerenone. Patients received either finerenone or a placebo, and the two groups were compared for the number of those whose disease progressed to a composite endpoint that included at least 40% reduction in kidney function, progression to kidney failure, or kidney death. A total of 504 of the 2,833 patients who received finerenone had at least one of the events in the composite endpoint, compared to 600 in the placebo arm. Of the patients who received finerenone, 367 experienced cardiovascular death, a nonfatal heart attack, nonfatal stroke, or hospitalization for heart failure, compared to 420 patients in the placebo arm. Treatment with finerenone was associated with hyperkalemia, hypotension, and hyponatremia. Patients with adrenal insufficiency and those receiving treatment with strong CYP3A4 inhibitors should not take finerenone.

Dapagliflozin (FARXIGA®)7 In April 2021, the FDA approved dapagliflozin (FARXIGA®) oral tablets to reduce risk of kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with CKD at risk for disease progression. This approval marked dapagliflozin as the first sodium-glucose transport protein 2 (SGLT2) inhibitor indicated for CKD in patients without Type 2 diabetes. A multicenter, double-blind study of 4,304 patients with CKD was conducted to evaluate the efficacy of dapagliflozin. Patients received either dapagliflozin or a placebo, and the two groups were compared for the number of patients with disease progression to a composite endpoint, including at least a 50% reduction in kidney function, progression to kidney failure, or cardiovascular or kidney death. Of the patients who received treatment, 197 of the 2,152 had at least one of the composite endpoints compared to 312 of

Table 1. Chronic Kidney Disease Pipeline8 Drug

Manufacturer

Route of Administration

Mechanism of Action

Status

CKD empagliflozin (JARDIANCE®)

Boehringer Ingelheim; Eli Lilly and Company

oral

SGLT2

phase three

ertugliflozin (STEGLATRO™)

Pfizer; Merck

oral

SGLT2

phase three

semaglutide (Ozempic®)

Novo Nordisk

GLP-1 agonist

phase three

diabetic nephropathy

CytoDyn

entry inhibitor

phase three

selonsertib (GS-4997)

Gilead

oral

ASK1 inhibitor

phase three

ARPKD/ADPKD

Tobira Therapeutics; Takeda Pharmaceutical Company

oral

entry inhibitor

phase two

tolvaptan (JYNARQUE® suspension)

Otsuka

oral

vasopressin antagonist

phase three

bardoxolone methyl

Reata Pharmaceuticals

oral

Nrf2 pathway activator

phase three

lixivaptan

Palladio Biosciences

oral

vasopressin antagonist

phase three

tesevatinib (KD019)

Kadmon

oral

receptor TKI

phase two

nalbuphine hydrochloride (Nalbuphine ER)

Trevi Therapeutics

oral

opioid agonist; opioid antagonist

phase three

difelikefalin (Korsuva (oral))

Cara Therapeutics

oral

opioid agonist

phase two

Uremic Pruritus

Abbreviations: ADPKD = autosomal dominant polycystic kidney disease; ARPKD = autosomal recessive polycystic kidney disease; ASK1 = apoptosis signal-regulating kinase 1; CKD = chronic kidney disease; GLP-1 = glucagon-like peptide-1; SGLT2 = sodium-glucose linked transporter 2; TKI = tyrosine kinase inhibitor

the 2,152 patients who received the placebo, and 100 patients who received treatment were hospitalized or died, compared to 138 patients who received the placebo. Adverse reactions associated with dapagliflozin included Fournier’s gangrene, dehydration, serious urinary tract infections, genital yeast infections, and metabolic acidosis or ketoacidosis. Prior to starting treatment with dapagliflozin, patients should be assessed for their volume status and kidney function and should consider a lower dose of insulin or insulin secretagogue to reduce the risk of hypoglycemia while on treatment.

Difelikefalin (Korsuva®)9, 10 In August 2021, the FDA approved difelikefalin (Korsuva®, Cara Therapeutics and Vifor Pharma) for treatment of moderate to severe pruritus associated with CKD in adults undergoing

hemodialysis. This injection is a first-in-class kappa opioid receptor that targets the peripheral nervous system. It was granted priority review by the FDA. Approval was based on evidence presented from two phase three trials. Results from the phase three KALM-1 trial showed that patients on 0.5 mcg/kg of difelikefalin achieved a three-point or greater improvement from baseline in the weekly mean of the daily 24-hour Worst Itch Intensity Numeric Rating Scale (WI-NRS) score; at week 12, it was 51% compared to 28% for patients on placebo. Additionally, 39% of patients on difelikefalin achieved a four-point or greater improvement in the weekly mean of WI-NRS score, compared to 18% of placebo patients. Patients on the difelikefalin injection also experienced both a 43% improvement in the average total Skindex-10 score and a 35% improvement in the average total 5-D itch score at week 12. Common adverse reactions reported were diarrhea, dizziness, nasopharyngitis, and vomiting.

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CHRONIC KIDNEY DISEASE | Continued

The U.S. Centers for Medicare & Medicaid Services released five payment models to reduce the development of end-stage kidney disease.

Payer Strategies for CKD Management With the growing number of older Americans, the number of people living with CKD will continue to increase, making CKD a priority for strategic management. Value-based models and care management programs that link providers and payers in an effort to align on improving outcomes and reducing costs seem likely to continue to trend in the CKD space. Data suggest that the cost burden of CKD increases substantially as the disease progresses, causing increased hospitalizations. Slowing disease progression and reducing the need for inpatient admission or readmission may result in cost reduction.2 Studies suggest that there is a high risk of potentially preventable hospitalizations among patients with higher CKD stages; in fact, in one study, nearly 50% of readmissions among patients with CKD were potentially avoidable, as these were most frequently due to diagnoses of heart failure, infection, renal failure, and ischemic heart disease.2, 11, 12 Comprehensive care that effectively manages CKD, underlying risk factors, and increasing comorbidities is key to effectively managing a growing population of patients with CKD.2 The U.S. Centers for Medicare & Medicaid Services (CMS) released five payment models to reduce the development of endstage kidney disease;13 these models are expected to enroll more Medicare patients in arrangements that incentivize providers to prevent CKD and comprehensively manage the health of CKD patients. The CMS Innovation Center released the EndStage Renal Disease Treatment Choices mandatory payment model, which enrolls all dialysis providers in approximately half of the country and provides incentives for at-home dialysis.11 Other models — the Kidney Care First and Comprehensive Kidney Care Contract — remain optional but assess new Medicare payment options with the objective of improving quality of care for CKD patients.13

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Several payers have turned to value-based kidney care arrangements, sometimes in partnership with kidney care programs, in an effort to manage costs and improve outcomes for member populations with CKD. BlueCross BlueShield Minnesota and DaVita Integrated Kidney Care entered an agreement comprised of four primary elements: 1. Targeted, coordinated care among program staff, nephrologists, and primary care providers. 2. Increasing awareness about CKD in order to catch the disease in its early stages and implement chronic disease management strategies earlier on in disease progression. 3. Use of data analytics as an additional method of identifying at-risk members. 4. Patient education via in-person and virtual channels to ensure proper awareness and understanding of CKD.14 Earlier in 2021, Cigna announced an expansion of its in-home kidney care program for Medicare Advantage members, which consists of regular home visits from care managers to help members living with CKD to manage health, improve outcomes, and reduce hospital admissions.15 Programs such as this one include a comprehensive care management team with case managers, social workers, physicians, nurses, and nephrologists to customize personal care plans, complete with medication therapy and comorbidity management and a focus on social determinants of health.15 Other payers and kidney care centers have announced collaborations as well, offering coordinated, holistic care for members with CKD; some of these programs include components such

as expanding care coordination services and transition care units for members recently diagnosed with kidney failure and value-based kidney care agreements.14, 15 The first approval of an SGLT2 inhibitor (dapagliflozin) to treat CKD in patients without Type 2 diabetes is a milestone in the CKD category and creates an opportunity to greatly expand the use of this therapeutic class. Agents in this class are widely covered by payers with minimal restrictions, but payers who manage this class with specific criteria may revisit and modify their policies based on labeling expansions to include coverage for CKD patients without Type 2 diabetes. Tools such as step therapy, prior authorization, and quantity limits may be effective in supporting payer objectives of managing costs and ensuring proper access to appropriate treatment for a growing CKD population.

The first approval of an SGLT2 inhibitor (dapagliflozin) to treat CKD in patients without Type 2 diabetes is a milestone in the CKD category and creates an opportunity to greatly expand the use of this therapeutic class.

References 1.

“Chronic Kidney Disease in the United States, 2021.” Centers for Disease Control and Prevention, 4 Mar. 2021, https://www.cdc.gov/ kidneydisease/publications-resources/ckd-national-facts.html. Golestaneh, Ladan, et al. “All-Cause Costs Increase Exponentially with Increased Chronic Kidney Disease Stage.” American Journal of Managed Care, 21 June 2017, https://www.ajmc.com/view/all-causecosts-increase-exponentially-with-increased-chronic-kidney-diseasestage-article.

IPD Analytics. “Chronic Kidney Disease.”

“FDA approves Korsuva as treatment for pruritus in patients on hemodialysis.” Healio News, 25 Aug. 2021, https://www.healio.com/ news/nephrology/20210825/fda-approves-korsuva-as-treatmentfor-pruritus-in-patients-on-hemodialysis.

10. “Cara Therapeutics Announces Positive Results from KALM-1 Pivotal Phase 3 Trial of KORSUVATM Injection in Hemodialysis Patients with Pruritus.” Cara Therapeutics, 29 May 2019, https:// www.globenewswire.com/news-release/2019/05/29/1856209/0/ en/Cara-Therapeutics-Announces-Positive-Results-From-KALM1-Pivotal-Phase-3-Trial-of-KORSUVA-Injection-in-HemodialysisPatients-with-Pruritus.html

“CKD Risk Factors and Prevention.” Centers for Disease Control and Prevention, 4 Mar. 2021, https://www.cdc.gov/kidneydisease/ publications-resources/annual-report/ckd-risk-prevention.html.

“CKD Related Health Problems.” Centers for Disease Control and Prevention, 4 Mar. 2021, https://www.cdc.gov/kidneydisease/ publications-resources/annual-report/ckd-related-health-problems. html.

11. Wiebe, Natasha, et al. “Potentially preventable hospitalization as a complication of CKD: a cohort study.” American Journal of Kidney Diseases, Aug. 2014, https://pubmed.ncbi.nlm.nih.gov/24731738/.

Verduzco, Hector Alvarado, et al. “CKD-Associated Pruritus: New Insights Into Diagnosis, Pathogenesis, and Management.” KIREPORTS, 10 May 2020, https://doi.org/10.1016/j.ekir.2020.04.027.

12. Donzé, Jacques, et al. “Causes and patterns of readmissions in patients with common comorbidities: retrospective cohort study.” The BMJ, 16 Dec. 2013, https://doi.org/10.1136/bmj.f7171.

“FDA Approves Drug to Reduce Risk of Serious Kidney and Heart Complications in Adults with Chronic Kidney Disease Associated with Type 2 Diabetes.” U.S. Food and Drug Administration, 9 July 2021, https://www.fda.gov/drugs/drug-safety-and-availability/fdaapproves-drug-reduce-risk-serious-kidney-and-heart-complicationsadults-chronic-kidney-disease.

13. Cox, Ryan. “Contributor: How Payers Can Be Effective in New ValueBased Models for CKD.” American Journal of Managed Care, 26 Dec. 2020, https://www.ajmc.com/view/contributor-how-payers-can-beeffective-in-new-value-based-models-for-ckd.

“FDA Approves Treatment for Chronic Kidney Disease.” U.S. Food and Drug Administration, 30 Apr. 2021, https://www.fda.gov/news-events/ press-announcements/fda-approves-treatment-chronic-kidneydisease.

14. Waddill, Kelsey. “Payer Launches Value-Based Kidney Care Agreement for CKD, ESKD.” HealthPayer Intelligence, 16 Apr. 2021, https://healthpayerintelligence.com/news/payer-launches-valuebased-kidney-care-agreement-for-ckd-eskd. 15. Nelson, Hannah. “Payer Boosts MA Chronic Kidney Management Access, Patient Outcomes.” HealthPayer Intelligence, 15 Mar. 2021, https://healthpayerintelligence.com/news/payer-boosts-ma-chronickidney-management-access-patient-outcomes.

Visit us online at magellanrx.com/mrxreport | 33

Magellan Capability Insight: Enhanced Utilization Management Program for High-Cost Therapies A new utilization management program reduces unnecessary healthcare spend.

Brian MacDonald, Pharm.D. Director, Specialty Clinical Strategy Magellan Rx Management

There are 7,000 known rare diseases and less than 10% have FDA-approved therapies. Despite this, orphan drugs are expected to account for $242 billion in drug spend — or one-fifth of all prescription sales — by 2024.1 The average cost of an orphan drug continues to rise, especially as more and more orphan drugs enter the market for ultra-rare disease states.1 Combined with increasingly expensive oncology treatments, there are more than 80 medical benefit drugs alone on the market with price tags over $300,000 per year. For example, chimeric antigen receptor T-cell (CAR-T) therapies were considered a cutting-edge treatment a few short years ago, but there are now a handful of options carrying a mean price tag over $400,000. In addition, multiple recent approvals on both the medical and pharmacy benefits to treat other rare diseases such as Duchenne muscular dystrophy and spinal muscular atrophy have average annual costs of over $500,000, all without including the headline-making $2.1 million cost of treatment with onasemnogene abeparvovec-xioi (ZOLGENSMA®). Payers and patients both face challenges in navigating new treatment options in the rare disease space. The surge of high-cost drug approvals presents challenges for payers aiming to develop effective management strategies. Clinical guidelines and literature to establish and support the standard of care for patients impacted by these diseases are often lacking, and appropriate prescribing requires specialized experience. On the other hand, patients are faced with the burden and potential mental health impact of their rare disease, possible comorbidities, identifying appropriate centers of excellence for treatment, navigating prior authorization and benefit structures within their health plans, and direct and nondirect monetary costs associated with their condition and treatment. Care management services may be a potential solution, relieving some of this burden for patients. One study demonstrated a reduction in

34 | Magellan Rx Report | Fall 2021

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hospital readmission rates from 52.6% to 18.4% in diabetic and heart failure patients who participated in an integrated case management program.2 Because medical resource utilization is so high in patients with complex, rare conditions, a similar benefit could be gained from comprehensive case management services that include holistic team care.

Magellan Rx Management’s Enhanced Utilization Management Program for High-Cost Therapies As a market leader in specialty drug management on both the pharmacy and medical benefits, we have developed a clinical solution to evaluate these high-cost treatments. Combining enhanced utilization management with access to supportive case management services, Magellan aims to drive optimal outcomes for members who have been prescribed high-cost medication (annual drug costs exceeding $300,000). The program successfully helps payers, medical directors, and provider networks by ensuring appropriate high-cost therapies are prescribed to the right members and avoiding unnecessary costs due to inappropriate use. Members also have access to case management,

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which provides them with high-touch services that a rare or orphan condition may require. Since early 2020, Magellan has partnered with health plans to embark on this strategy, since cost avoidance due to inappropriate use for just one member will lead to significant annual savings. As a result, clients have already experienced millions of dollars in cost avoidance through high-quality, personalized reviews for members prescribed high-cost therapies for rare and orphan diseases. Magellan is excited to continue to roll out similar strategies for new and existing clients in the near future.

References 1.

“Orphan Drug Report 2019: 6th Edition.” Evaluate Pharma, Apr. 2019, https://www.evaluate.com/sites/default/files/media/download-files/ EvaluatePharma_Orphan_Drug_Report_2019.pdf.

McCants, Khalilah, et al. “The Impact of Case Management on Reducing Readmission for Patients Diagnosed With Heart Failure and Diabetes.” Professional Case Management, July/Aug. 2019, https:// pubmed.ncbi.nlm.nih.gov/31145236/.

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Magellan Method

AT MAGELLAN METHOD, we are uniquely qualiﬁed to solve

complex healthcare challenges. As a subsidiary of Magellan Health, a Fortune 500 company, we have access to a wide range of resources and expertise from across our PBM, Medicare, and behavioral health divisions. We leverage up-to-date healthcare data to implement solutions that transform how care is delivered. Our team of analytic experts partners with you to develop a customized solution that delivers results.

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Dry Eye Disease: Changing Treatment and Management Landscape As the dry eye disease pipeline expands, preferential formulary tiering, step therapy, and formulary exclusion may all allow patients access to safe and effective therapies, while managing costs and ensuring appropriate use. Dry eye disease (DED) is a common, chronic, episodic, multifactorial disease that affects the tears and ocular surface. The condition is characterized by failure to produce high-quality tears or a sufficient amount of tears to moisturize the eyes.1 The condition can involve tear film instability, inflammation, discomfort, visual disturbance, and ocular surface damage.1 The prevalence of DED is not accurately known; estimates range from 5% to 50% and can be as high as 75% among adults over age 40. About 16 to 20 million Americans live with DED, according to various estimates.2, 3, 4 DED is significantly less prevalent among adults between ages 18 and 45, affecting only approximately 2.7% of people in this age range.3, 5 Women are more likely to experience DED than men.3, 5 Lindsay C. Speicher, J.D. Project Manager Magellan Method

Despite DED’s serious vision and quality-of-life consequences, the condition remains misdiagnosed or undiagnosed and undertreated. A study showed that patients whose DED went undiagnosed and untreated had a significant decline in their dry eye-related quality-of-life score; untreated DED can often become chronic and progressively more severe.6 DED is diagnosed via a comprehensive exam that includes a refraction evaluation to determine best-corrected visual acuity and assessment of the orbital structures. Additional tests to evaluate the cornea and tear film layer include a slit-lamp biomicroscopy exam, a tear film breakup time test, and the Schirmer’s test to measure tear production from the lacrimal glands.3 Symptoms of DED include a scratchy, stinging, or burning feeling in the eyes; red eyes; sensitivity to light; and blurry vision.1 Higher-risk individuals include women, those over the age of 50, those with inadequate intake of vitamin A or omega-3 fatty acids, and those living with certain autoimmune conditions.1 Patients with DED may experience an improvement in symptoms by limiting the length of time spent looking at computer screens, tablets, or smartphones. In the long term, if severe DED is undertreated or left untreated, cornea damage can occur.1 The estimated cost to manage a patient with DED is $783 annually from the payer perspective.

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DRY EYE DISEASE | Continued

Trends to keep an eye on Ophthalmic Injections 2020 ELEV ENTH

EDITION

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Given the high prevalence of DED, the overall cost burden to the U.S. healthcare system is about $3.84 billion.7 Societally, DED carries a burden of $11,302 per patient annually and $55.4 billion overall, including direct and indirect costs.7

DED Treatment DED is commonly treated with over-the-counter (OTC) eye drops called artificial tears; other OTC products such as moisturizing gels and ointments can also provide relief.1, 8 There are six FDA-approved therapies indicated for DED, three (Restasis®, Restasis MultiDose®, and CEQUA™) containing cyclosporine as the active ingredient. Lifestyle modifications may improve DED symptoms and include avoiding smoke, wind, or air conditioning; use of a humidifier; limiting screen time; wearing sunglasses; staying hydrated; and getting sufficient sleep. In addition, medications associated with DED such as antihistamines and tricyclic antidepressants can be adjusted or discontinued to help improve DED symptoms when appropriate.1, 8

Treatment Guidelines9 Guidelines published by the American Academy of Ophthalmology (AAO) in 2018 note that pharmacological and procedural treatments can be associated with improvements in symptoms and clinical signs of DED. The AAO notes

38 | Magellan Rx Report | Fall 2021

elimination of exacerbating factors to be one of the first recommended steps in managing mild DED. With continued symptoms, artificial tears should be used. Prescription drug treatment is recommended for moderate to severe DED; specifically, topical cyclosporine is recommended, has been shown to have clinical benefit, and in some cases can lead to long-term treatmentfree remission for patients. Lifitegrast (Xiidra®), a lymphocyte function-associated antigen-1 antagonist, has shown benefit in signs and symptoms of DED; however, long-term efficacy and safety are unknown.

Loteprednol etabonate ophthalmic suspension (Eysuvis®)10, 11 In October 2020, the FDA approved loteprednol etabonate ophthalmic suspension (Eysuvis®, Kala Pharmaceuticals) as the first ocular corticosteroid for short-term treatment of DED. Approval was granted based on clinical trial results that demonstrated significant improvements in the signs and symptoms of DED. In all phase three trials, statistically significant results were achieved for the endpoint of conjunctival hyperemia after two weeks of dosing. Two of the three phase three trials demonstrated statistical significance for the symptom endpoints of ocular discomfort and severity in both the overall intent-to-treat (ITT) population and in a predefined subgroup of ITT patients with more severe ocular discomfort.

Table 1. DED Expanded Pipeline Drug

Manufacturer

Route of Administration

Mechanism of Action

Status

varenicline (OC-01)

Oyster Point Pharma

nasal

nAChR agonist

pending (10/17/2021)

cyclosporine (CyclASol®)

Novaliq

ophthalmic

immunosuppressant

phase three

timbetasin (RGN-259)

ReGenTree; RegeneRx Biopharmaceuticals

ophthalmic

actin modulator; apoptosis inhibitor

phase three

tavilermide (MIM-D3)

Mimetogen Pharmaceuticals; Allergan

ophthalmic

TrkA receptor agonist

phase three

reproxalap (ADX-102)

Aldeyra Therapeutics

topical; ophthalmic

aldehyde inhibitor

phase three

etanercept (HL036)

HanAll Biopharma; Daewoong Pharmaceutical

ophthalmic

TNF-alpha inhibitor

phase three

SkQ1

Mitotech; OraPharma

ophthalmic

antioxidant

phase three

perfluorohexyloctane (NOV03)

Novaliq; Bausch Health

ophthalmic

lipid layer stabilizer

phase three

BRM421

BRIM Biotechnology

ophthalmic

corneal LSC stimulator

phase three

OmegaD Softgels

Omega Pharma

oral

omega-3 fatty acids and derivatives

phase three

tivanisiran sodium (SYL1001)

SYLENTIS; PharmaMar

ophthalmic

siRNA

phase three

ALY688

Allysta Pharmaceuticals

ophthalmic

adiponectin receptor agonist

phase three

Abbreviations: LSC = limbal stem cell; nAChR = nicotinic acetylcholine receptor antagonist; siRNA = small interfering RNA; TBD = to be determined; TNF = tumor necrosis factor; TrkA = tropomyosin receptor kinase A

Pipeline Varenicline (OC-01) Varenicline (OC-01, Oyster Point Pharma), a nicotinic acetylcholine receptor agonist administered as a nasal spray, is currently under FDA review for DED. In the phase three ONSET-2 study of varenicline nasal spray, 758 patients were randomized to receive one of two doses of varenicline (0.6 mg/mL for 260 patients and 1.2 mg/mL for 246 patients) or a placebo (for 252 patients) twice daily for 28 days. Results showed that the varenicline group experienced greater improvement in Schirmer’s test score (a gain of 10 mm or more from the base-

line by day 28) compared to the placebo group. When comparing the two varenicline groups, 47.3% of the 0.6 mg/mL group showed improvement, while 49.2% of the 1.2 mg/mL group showed improvement; in the placebo group, 27.8% showed improvement. Both varenicline groups experienced greater reduction in eye dryness score from the baseline at week 2 compared to the placebo group. The most common adverse reaction reported was sneezing. The FDA’s decision to approve varenicline nasal spray is expected on Oct. 17, 2021.

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DRY EYE DISEASE | Continued

Management Strategies Currently, cyclosporine is the primary prescription agent used in the treatment of DED, and the cyclosporine treatment landscape is set to expand. With single-use Restasis® potentially losing exclusivity in 2021 and a new cyclosporine product in the pipeline, payer management strategies for DED may shift. New competition in the DED space may decrease costs, specifically with the launch of generic alternatives. Additionally, the potential approval of varenicline nasal spray alternative therapy may alleviate some of the unmet need in the DED population as this unique route of administration may appeal to DED patients who are averse to self-administering eye drops. Pricing is unknown, but this agent may be priced higher due to its route of administration.

Blazing the trail for better

Specialty Drug Management

Utilization management strategies will continue to be key in this category. Payer tools may help guide patients toward effective lower-cost products. Preferential formulary tiering, step therapy, and formulary exclusion may all allow patients access to safe and effective therapies for DED while managing costs and ensuring appropriate use. Policy and formulary development should focus on the availability of generics in the coming year.

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References 7.

Stapleton, Fiona, et al. “TFOS DEWS II Epidemiology Report.” The Ocular Surface, July 2017, https://pubmed.ncbi.nlm.nih. gov/28736337/.

Yu, Junhua, et al. “The economic burden of dry eye disease in the United States: a decision tree analysis.” Cornea, Apr. 2011, https:// pubmed.ncbi.nlm.nih.gov/21045640/.

Rouen, Patricia, and Mary White. “Dry Eye Disease: Prevalence, Assessment, and Management.” Home Healthcare Now, Mar./Apr. 2018, https://pubmed.ncbi.nlm.nih.gov/29498987/.

Kenny, Kathleen. “Dry Eye Disease: Higher Rates in View.” Pharmacy Times, 11 May 2017, https://www.pharmacytimes.com/view/dry-eyedisease-higher-rates-in-view.

“2016 Dry Eye Products Report: A Global Analysis for 2015 to 2021.” Market Scope, 2016.

“Dry Eye Syndrome PPP – 2018.” American Academy of Ophthalmology, Nov. 2018, https://www.aao.org/preferred-practicepattern/dry-eye-syndrome-ppp-2018.

Farrand, Kimberly, et al. “Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older.” American Journal of Ophthamology, Oct. 2017, https://pubmed.ncbi.nlm.nih. gov/28705660/.

10. “Kala Pharmaceuticals Announces FDA Approval of EYSUVIS™ for the Short-Term Treatment of the Signs and Symptoms of Dry Eye Disease.” BioSpace, 27 Oct. 2020, https://www.biospace.com/article/ releases/kala-pharmaceuticals-announces-fda-approval-of-eysuvisfor-the-short-term-treatment-of-the-signs-and-symptoms-of-dryeye-disease/.

Yamanishi, Ryutaro, et al. “Characteristics of Individuals with Dry Eye Symptoms Without Clinical Diagnosis: Analysis of a Web-Based Survey.” Journal of Clinical Medicine, 21 May 2019, https://pubmed. ncbi.nlm.nih.gov/31117304/.

11. “FDA approves Eysuvis for short-term dry eye disease treatment.” Healio News, 27 Oct. 2020, https://www.healio.com/news/ ophthalmology/20201027/fda-approves-eysuvis-for-shortterm-dryeye-disease-treatment.

“Dry Eye.” National Eye Institute, 22 Dec. 2020, https://www.nei.nih. gov/learn-about-eye-health/eye-conditions-and-diseases/dry-eye.

40 | Magellan Rx Report | Fall 2021

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