31 minute read
4 value-based contracting strategies
By Karen Blum
Chicago—Value-based contracts (VBCs) provide an opportunity for manufacturers to evaluate outcomes not studied in clinical trials, while offering payors attractive pricing.
Speakers at a panel discussion at the AMCP 2022 annual meeting provided insight into these benefits, along with an assessment of the VBC marketplace and advice on how payors can pursue such contracts.
“I see this as an organized scramble right now,” Paul Jeffrey, PharmD, the principal at Paul Jeffrey Consulting and retired senior director of pharmacy for MassHealth, the Massachusetts Medicaid program, said during the discussion.
Rapid Growth
VBCs can be traced to the 1930s, with the start of managed payment plans, Dr. Jeffrey noted. At that time, he said, it wasn’t about value as much as a way for people to purchase healthcare.
Over the past 30 years, payors have shifted from paying for service to quality and then to value, he said. The term “value-based care” was introduced in the early part of this century, he said, and has progressed continually with the formation of accountable care organizations. “Value-based contracts” as a term began entering the literature and lexicon starting around 2010.
The number of publicly disclosed VBCs increased from two in 2009 to 19 in 2018, representing eight therapeutic areas, said Mahsa Salsabili, PharmD, PhD, a pharmacoeconomics specialist at University of Massachusetts Chan Medical School, in Shrewsbury. Cardiology and neurology have been the top therapeutic areas covered by VBCs, followed by endocrinology, she said.
Several types of contracts exist today, Dr. Jeffrey said. There are warranties, in which payors get their money back if a product doesn’t work. Some contracts allow payors to spread out payments for drugs. Subscription models allow payors to pay one price to treat as many beneficiaries as needed. And hybrid models combine elements of these different plans.
“All of these are undergoing evaluation,” Dr. Jeffrey said. “This market is anything but settled.”
4 Negotiating Stages
MassHealth’s team goes through four stages during direct negotiations with manufacturers, said Neha Kashalikar, PharmD, a clinical pharmacist with the Office of Clinical Affairs, the MassHealth clinical decision support unit staffed by UMass Chan Medical School. The multidisciplinary team includes clinical and operational pharmacists who lead negotiations, evaluate offers and implement new contracts. They are backed up by senior leadership, pharmacoeconomics specialists, data analysts, and legal and information technology supports.
1Team members meet with manufacturers frequently, often several times a week to discuss pipeline products, or proposed value-based or supplemental rebate agreements.
2Once a contracting proposal has been submitted, the team conducts a thorough review, including clinical evaluation of current evidence-based medicine as well as a review of any market trends or pricing, coupled with utilization data. The team then compiles a fiscal analysis to determine savings that may come from the contract. When appropriate, the team consults other stakeholders, such as physicians, to ensure alignment around the proposed contract terms.
3Once the team and other stakeholders agree on the proposed contract terms, MassHealth enters into negotiations with the manufacturer to ensure the contract provides the greatest value to the state program.
4Then, they work to put the agreement in place. This includes implementing any criteria changes to the MassHealth drug list, communicating to providers about upcoming changes and coordinating with managed care organization plans to ensure alignment in formulary decisions. Most contracts signed by the program are for one year, Dr. Kashalikar said.
MassHealth takes a proactive approach to identifying high-priority drugs for contracting on the basis of how they may provide value to the program, she said. Her team runs a focused report each year to identify drugs that are high cost, that have a high averageper-member per-year cost, that have low rebates and those with increasing utilization among their beneficiaries. Once high-priority drugs are identified, a pharmacoeconomics specialist helps the team further refine its priority based on market landscape, utilization data, international pricing and other characteristics, to determine which drugs may be most successful for negotiation.
It’s important to be wary of scenarios where contract terms may potentially put a plan at odds with best practice, Dr. Kashalikar cautioned.
To date, MassHealth has reached agreements for supplemental rebates with 17 manufacturers for 45 drugs, for a nearly $201 million annual value, Dr. Kashalikar said. The program has eight value-based agreements in place, one for a novel digital therapeutic product, and continues to have ongoing negotiations with manufacturers for many medications.
VBCs Versus Supplemental Rebate Agreements
One of the first questions the team members ask themselves is whether a particular drug is better suited for a VBC or a supplemental rebate agreement, in which a manufacturer may provide an enhanced rebate (on top of the federal rebate) for preferred status for its product compared with clinical competitors, Dr. Kashalikar said. Drugs well suited for VBCs include those that may have been approved based on biomarkers, those with limited real-world evidence and those in which there is a question surrounding safety and efficacy. It allows the manufacturer to stand behind the expected outcomes of a drug.
On the flip side, those more suited to supplemental rebate agreements include drugs with established safety and efficacy data; those with a high monitoring or administration cost; and with patient-reported outcomes. High-cost drugs, pipeline products and those with increasing utilization fall in the middle and could be suitable for either arrangement, she said.
It’s important for payors and manufacturers to work together to identify the best endpoints for value-based contracts. Those end points should be clinically relevant, tracked as part of routine patient care and able to be reported easily by providers or office staff. Contracts must be structured in a manner that is operationalizable with an objective end point that can be tracked either on a prior authorization form or through pharmacy or medical claims data.
Next Steps
Future trends to look for include continued state legislation in this area; publications of evaluations on the utility of value-based agreements; the evolution of a standardized approach to contracts; the solidification of best practices; and the application of VBCs to digital therapeutics, Dr. Jeffrey said.
“I don’t think that value-based contracting is going to go away,” he said. “I think it’s going to continue to escalate and become more prevalent.”
—Paul Jeffrey, PharmD
manufacturers for 45
drugs, for a nearly $201
million
annual value.
Provider Status Boost
continued from page 1
Legislation had been introduced to include pharmacists as providers in the state. Meanwhile, healthcare reform was trending toward value-based care, which led to pharmacists being more involved in patient care activities nationwide. Finally, there was much scrutiny of pharmacy benefit manager (PBM) practices in the state, particularly within the Medicaid program. This issue was covered widely in state media, “allowing legislators and the public to become aware of … the pharmacy model, [and] also the potential for the pharmacist to be an untapped resource for access to a potentially lower-cost healthcare model,” said Dr. Beatty, who is also an associate professor of clinical pharmacy at The Ohio State University College of Pharmacy, in Columbus, during a panel discussion.
Pharmacist provider status, as covered under Ohio Senate Bill 265, was signed into law in January 2019, Dr. Beatty said. It permitted insurers to cover pharmacist services and allowed programs to start without any type of mandate. From there, the OPA began working with the state’s five Medicaid managed care organizations on plans to accept pharmacists as providers. Once pharmacists sign up for a Medicaid ID number and enroll with Medicaid plans, they can begin billing as a provider if all rules are met.
Focusing on Rural Areas
CareSource, a health plan based in Dayton, worked with one pharmacy in the rural area of Camden and another in an underserved community near downtown Dayton, said Nicholas Trego, PharmD, RPh, the company’s associate vice president of the Ohio Pharmacy Market. They focused on four areas: smoking cessation, diabetes care, asthma control and naloxone therapy for patients taking opioids.
OPA worked with pharmacists and the CareSource team to assist with implementation of the services. Documentation and billing templates were created, and the OPA team helped guide pharmacists through visits, monitoring of patients and implementation of the new program. The CareSource team also attended calls to ensure appropriate patient selection, make sure pharmacists knew about other resources available from the health plan and ascertain appropriate data collection.
Looking at the effectiveness of pharmacists’ interventions, 80% of patients had improvements in asthma control test scores; 75% experienced a reduction in blood glucose; 50% reduced their tobacco use; 89% started on tobacco cessation medications; and three patients were counseled and given naloxone. There were anecdotes of success as well, Dr. Trego said, such as a pharmacist detecting a foot ulcer in one patient with diabetes, and obtaining a nebulizer within two days for another patient with asthma who had been going to a hospital emergency department (ED) weekly for breathing treatments. Along the way, pharmacists asked for the ability to order laboratory tests to help with work on hemoglobin A1c (HbA1c) levels for people with diabetes.
“That’s a really big gap pharmacists are able to fill in for health plans,” Dr. Trego said. “A1c testing is very important to have. It’s associated with the National Committee for Quality Assurance’s HEDIS (healthcare effectiveness data and information set) metrics, so that is another really big opportunity for this to expand in the future.”
Pharmacists Pitch In During COVID-19
In what Dr. Trego said was perhaps his favorite story about the effectiveness of the program, he cited the experience of two physicians at the medical practice near the Camden pharmacy who came down with COVID-19 at the same time and had to close their office for two weeks. CareSource allowed pharmacists to see patients for any disease state during that period to avoid having to shuttle patients 45 minutes each way from Camden to Dayton to be seen by another physician. “How much cooler of a story can you have than pharmacists stepping in and taking care of the healthcare for the town?” Dr. Trego noted.
When the Ohio legislation passed, Buckeye Health Plan, part of Centene Corporation, was starting to hear enthusiasm from hospital systems and others wanting to hire pharmacists but looking for programs to show outcomes and return on investment to leadership, said Meera Patel-Zook, PharmD, the vice president of pharmacy operations for the health plan. In some cases, healthcare entities had pharmacists on staff, but not an established way to get reimbursed for their time.
To start, the plan focused on working with two federally qualified health centers and one hospital system before expanding to other pharmacies. They worked through a collaborative practice agreement to focus on HEDIS measures and holistic disease state management for conditions such as diabetes, cardiovascular disease, asthma, behavioral health and other chronic conditions, with the goals of reducing healthcare spending, improving member experience and enhancing provider partnerships. Monthly dashboards were provided to pharmacists to give them information about which patients had potential gaps in care, such as uncontrolled HbA1c levels or elevated blood pressure. The teams also partnered with OPA for discussions on new workflow and billing practices. “Eventually, we wanted to be able to show that this model that we’re creating can decrease inpatient visits, decrease ED visits,” Dr. Patel-Zook said. “Post-utilization from this should be favorable.”
So far, the program has about six months of claims data, but the three locations are showing that with pharmacist intervention, members have been 18% more likely to get routine vaccinations, 17% more likely to have blood pressure under control and 32% more likely to get a COVID-19 vaccine than in other practices without pharmacist involvement, she said.
Anecdotes also have been favorable, Dr. Patel-Zook noted. In one case, a pharmacist had a 45-minute conversation with a member whose HbA1c level was more than 13%. While they talked, the pharmacist observed the member was becoming hypoglycemic, so she gave her some food. They also discovered the person was living on her son’s couch in an unsafe area, and had anxiety as a result. The pharmacist linked the patient to the health plan’s social determinants of health care coordination team, which connected the member to stable housing.
Since then, the member’s HbA1c level has fallen to 6% in less than six months. The person now is on antianxiety medication, is adherent to diabetes medication and has had her artwork featured in local newspapers.
Molina Healthcare Takes Different Approach
Molina Healthcare of Ohio used a different strategy, allowing pharmacists at 10 independent pharmacies in the state to treat patients for conditions as they saw a need, said Kimberly Broyles-Kpogli, PharmD, MBA, the company’s director of pharmacy. “We didn’t want them to just think about diabetes, hypertension or respiratory concerns,” she said. “We knew that they would because a lot of our members have those conditions, but we didn’t want the pharmacists to feel they were in a box. We wanted them to provide care to patients where it was needed because these pharmacists likely knew our patients better than we did at the health plan.”
Pharmacists provided various interventions and services such as administering vaccinations, counseling for medications and their side effects, and offering smoking cessation and diabetes education. One pharmacy chose to pursue behavioral health and developed a pharmacist intervention for depression and anxiety conditions.
In this program, pharmacists administered standardized Patient Health Questionnaire-9 (PHQ9) or Generalized Anxiety Disorder (GAD7) tests to patients who regularly filled antidepressant or antianxiety medications, to assess their mental states. The site thought this was especially important given the effect of the COVID-19 pandemic on mental health and access to primary care services. After obtaining baseline scores, pharmacists worked to educate members about the medications, ensured adherence, provided counseling to optimize therapy effectiveness and made recommendations to providers if needed. Over a sixmonth period, pharmacists met with 43 patients. About 73% of patients had stable or improved PHQ9/GAD7 scores after pharmacist follow-up.
Pharmacists participating in the programs were invited to join group phone calls with OPA for troubleshooting and sharing advice. Overall, pharmacists have loved their experiences, Dr. Beatty said. “The programs recognizing pharmacists as providers are creating an incentive in the healthcare model that is fully taking advantage of the training of pharmacists. Our pharmacists are saying, ‘This is the reason I went to school. I want to get back to actually taking care of these patients that I’ve seen sometimes for 10 to 15 years and help them be healthier.’ We look forward to the continuation of this program in Ohio and other states that allow pharmacists to add to the high level of care that should be expected by patients.”
With pharmacist intervention, members have been 18%
more likely
to get routine vaccinations, 17%
more likely
to have blood pressure under control and 32%
more likely
to get a COVID-19 vaccine than in other practices without pharmacist involvement.
For patients with cGVHD ROCK ON
INDICATION
IMPORTANT SAFETY INFORMATION
Warningsand Precautions
• Embryo-Fetal Toxicity: administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with
Adverse Reactions
• • •
Drug Interactions
• Strong CYP3A Inducers: Coadministration of REZUROCK with strong CYP3A inducers decreases belumosudil when coadministered with strong CYP3A inducers • Proton Pump Inhibitors: Coadministration of REZUROCK with proton pump inhibitors decreases belumosudil when coadministered with proton pump inhibitors
ORRa 75%
(95% CI, 63-85; P<.0001)1,4
REZUROCK achieved clinically and statistically with the 200-mg once-daily dose in a real-world demographic of patients with cGVHD.1
• 1-3 • CR was observed in all organs 5
• There was no death or new systemic therapy initiation in 62%
(95% CI, 46-74) of the responder population at 12 months1 • Clinically meaningful improvements in QOL,with CS and CNI dose reductions and discontinuations and nonresponders5
• Well tolerated1
ASSIST ™
Enroll your patients with cGVHD in Kadmon ASSIST so our Kadmon ASSIST Monday through Friday, 8 -8 ET, 1-844-KADMON1 (523-6661).
VISIT REZUROCKhcp.com TO LEARN MORE
cGVHD, chronic graft-versus-host disease; CNI, calcineurin inhibitor; CR, complete response; CS, corticosteroid; FDA, US Food and Drug Administration; NIH, National Institutes of Health; ORR, overall response rate; PR, partial response; QOL, quality of life; ROCK2, rho-associated coiled-coil–containing protein kinase-2. aProportion of patients who achieved CR or PR according to the 2014 NIH cGVHD Consensus Criteria in the 200-mg once-daily arm.1
IMPORTANT SAFETY INFORMATION (cont)
• Pregnancy: administered to pregnant women. There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. Advise pregnant women and females of reproductive potential of the potential risk to the fetus • Lactation: There are no data available on the presence of belumosudil or its metabolites in human milk or the effects on after the last dose • Pediatric Use: The safety and effectiveness of REZUROCK have been established in pediatric patients 12 years and older.
The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established • Geriatric Use: clinically meaningful differences in safety or effectiveness of REZUROCK were observed in comparison to younger patients • Renal and Hepatic Impairment: Treatment with REZUROCK has not been studied in patients with pre-existing severe You are encouraged to report side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call
References: 1. REZUROCK. Package insert. Kadmon Pharmaceuticals, LLC; 2021. 2. Zanin-Zhorov A, Weiss JM, Nyuydzefe MS, et al.Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proc Natl Acad Sci USA. 2014;111(47):16814-16819.doi:10.1073/pnas.1414189111 3. Flynn R, Paz K, Du J, et al. Targeted rho associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism. Blood.2016;127(17):2144-2154. doi:10.1182/blood-2015-10-678706 4. 5. Cutler CS, Lee SJ, Arai S, et al. Belumosudil for chronic graft-versus-host disease (cGVHD) after 2 or more prior lines of therapy: the ROCKstar study. Blood. 2021;blood.2021012021. doi:10.1182/blood.2021012021
Please see Brief Summary of full Prescribing Information on adjacent pages.
REZUROCK™ (belumosudil) tablets, for oral use Initial U.S. Approval: 2021 BRIEF SUMMARY: Please see package insert for full prescribing information. 1 INDICATIONS AND USAGE
REZUROCK is indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versushost disease (chronic GVHD) after failure of at least two prior lines of systemic therapy.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS 5.1 Embryo-Fetal Toxicity
Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period organogenesis caused adverse developmental outcomes including embryo-fetal mortality and malformations at maternal exposures (AUC) less than those in patients at the recommended dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose [see Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1) in the full prescribing information].
6 ADVERSE REACTIONS 6.1 Clinical Trial Experience
Because clinical trials are conducted under widely variable conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice. Chronic Graft versus Host Disease In two clinical trials (Study KD025-213 and Study KD025-208), 83 adult patients with chronic GVHD were treated with REZUROCK 200 mg once daily [see Clinical Studies (14.1) in the full prescribing information]. The median duration of treatment was 9.2 months (range 0.5 to 44.7 months). Fatal adverse reaction was reported in one patient with severe nausea, vomiting, diarrhea and multi-organ failure. Permanent discontinuation of REZUROCK due to adverse reactions occurred in 18% of patients. The adverse reactions which resulted in permanent discontinuation of REZUROCK in > 3% of patients included nausea (4%). Adverse reactions leading to dose interruption occurred in 29% of patients. The adverse reactions leading to dose interruption in ≥ 2% were infections (11%), diarrhea (4%), and asthenia, dyspnea, hemorrhage, hypotension, liver function test abnormal, nausea, pyrexia, edema, and renal failure with (2% each). The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension. Table 2 summarizes the nonlaboratory adverse reactions.
a infection with an unspecified pathogen includes acute sinusitis, device related infection, ear infection, folliculitis, gastroenteritis, gastrointestinal infection, hordeolum, infectious colitis, lung infection, skin infection, tooth infection, urinary tract infection, wound infection, upper respiratory tract infection, pneumonia, conjunctivitis, sinusitis, respiratory tract infection, bronchitis, sepsis, septic shock. b includes influenza, rhinovirus infection, gastroenteritis viral, viral upper respiratory tract infection, bronchitis viral, Epstein-Barr viremia, Epstein-Barr virus infection, parainfluenzae virus infection, Varicella zoster virus infection, viral infection. c includes cellulitis, Helicobacter infection, Staphylococcal bacteremia, catheter site cellulitis, Clostridium difficile colitis, Escherichia urinary tract infection, gastroenteritis Escherichia coli, Pseudomonas infection, urinary tract infection bacterial. d includes fatigue, asthenia, malaise. e includes edema peripheral, generalized edema, face edema, localized edema, edema. f includes nausea, vomiting. g includes abdominal pain, abdominal pain upper, abdominal pain lower. h includes dyspnea, dyspnea exertional, apnea, orthopnea, sleep apnea syndrome. i includes cough, productive cough. j includes contusion, hematoma, epistaxis, increased tendency to bruise, conjunctival hemorrhage, hematochezia, mouth hemorrhage, catheter site hemorrhage, hematuria, hemothorax, purpura. k includes pain in extremity, back pain, flank pain, limb discomfort, musculoskeletal chest pain, neck pain, musculoskeletal pain. l includes headache, migraine. m includes rash, rash maculo-papular, rash erythematous, rash generalized, dermatitis exfoliative. n includes pruritus, pruritus generalized. Table 3 summarizes the laboratory abnormalities in REZUROCK.
7 DRUG INTERACTIONS 7.1 Effect of Other Drugs on REZUROCK
Strong CYP3A Inducers Coadministration of REZUROCK with strong CYP3A inducers decreases belumosudil exposure [see Clinical Pharmacology (12.3) in the full prescribing information], which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when coadministered with strong CYP3A inducers [see Dosage and Administration (2.3) in the full prescribing information]. Proton Pump Inhibitors Coadministration of REZUROCK with proton pump inhibitors decreases belumosudil exposure [see Clinical Pharmacology (12.3) in the full prescribing information], which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when coadministered with proton pump inhibitors [see Dosage and Administration (2.3) in the full prescribing information].
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy
Risk Summary Based on findings from animal studies and the mechanism of action [see Clinical Pharmacology (12.1) in the full prescribing information], REZUROCK can cause fetal harm when administered to pregnant women. There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes, including alterations to growth, embryo-fetal mortality, and embryo-fetal malformations at maternal exposures (AUC) approximately ≥ 3- (rat) and ≥ 0.07 (rabbit) times the human exposure (AUC) at the recommended dose (see Animal Data). Advise pregnant women and females of reproductive potential of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Embryo-fetal development studies were conducted in rats with administration of belumosudil to pregnant animals during the period of organogenesis at oral doses of 25, 50, 150, and 300 mg/kg/day in a pilot study and doses of 15, 50, and 150 mg/kg/day in a pivotal study. In the pilot study, maternal toxicity and embryo- fetal developmental effects were observed. Maternal toxicity (reduced body weight gain) occurred at 150 and 300 mg/kg/day doses. Increased post-implantation loss occurred at 50 and 300 mg/kg/day. Fetal-malformations were observed at ≥ 50 mg/kg/day and included absence of anus and tail, omphalocele, and dome shaped head. The exposure (AUC) at 50 mg/kg/day in rats is approximately 3 times the human exposure at the recommended dose of 200 mg. In an embryo-fetal developmental study in rabbits, pregnant animals administered oral doses of belumosudil at 50, 125, and 225 mg/kg/day during the period of organogenesis resulted in maternal toxicity and embryo-fetal developmental effects. Maternal toxicity (body weight loss and mortality) was observed at doses ≥ 125 mg/kg/day. Embryo-fetal effects were observed at doses ≥ 50 mg/kg/day and included spontaneous abortion, increased post-implantation loss, decreased percentage of live fetuses, malformations, and decreased fetal body weight. Malformations included those in the tail (short), ribs (branched, fused or deformed), sternebrae (fused), and neural arches (fused, misaligned, and deformed). The exposure (AUC) at 50 mg/kg/day in rabbits is approximately 0.07 times the human exposure at the recommended dose of 200 mg.
8.2 Lactation
Risk Summary There are no data available on the presence of belumosudil or its metabolites in human milk or the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions from belumosudil in the breastfed child, advise lactating women not to breastfeed during treatment with REZUROCK and for at least one week after the last dose.
8.3 Females and Males of Reproductive Potential
REZUROCK can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating treatment with REZUROCK.
Table 2: Nonlaboratory Adverse Reactions in ≥ 10% Patients with Chronic GVHD Treated with REZUROCK
Adverse Reaction REZUROCK 200 mg once daily (N=83) All Grades (%) Grades 3-4 (%)
Infections and infestations
Infection (pathogen not specified)a Viral infectionb Bacterial infectionc
General disorders and administration site conditions
Astheniad 53 16 19 4 16 4
46 4 Edemae 27 1 Pyrexia 18 1
Gastrointestinal
Nauseaf 42 4 Diarrhea 35 5 Abdominal paing 22 1 Dysphagia 16 0
Respiratory, thoracic and mediastinal
Dyspneah 33 5 Coughi 30 0 Nasal congestion 12 0
Vascular
Hemorrhagej 23 5 Hypertension 21 7
Musculoskeletal and connective tissue
Musculoskeletal paink 22 4 Muscle spasm 17 0 Arthralgia 15 2
Nervous system
Headachel 21 0
Metabolism and nutrition
Decreased appetite 17 1
Skin and subcutaneous
Rashm 12 0 Pruritusn 11 0
Table 3: Selected Laboratory Abnormalities in Patients with Chronic GVHD Treated with REZUROCK REZUROCK 200 mg once daily
Grade 0-1 Baseline Grade 2-4 Max Post
Grade 3-4 Max Post Parameter (N) (%) (%) Chemistry
Phosphate Decreased 76 28 7 Gamma Glutamyl Transferase Increased 47 21 11 Calcium Decreased 82 12 1 Alkaline Phosphatase Increased 80 9 0 Potassium Increased 82 7 1 Alanine Aminotransferase Increased 83 7 2 Creatinine Increased 83 4 0
Hematology
Lymphocytes Decreased 62 29 13 Hemoglobin Decreased 79 11 1 Platelets Decreased 82 10 5 Neutrophil Count Decreased 83 8 4
Contraception Females Advise females of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose of REZUROCK. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose of REZUROCK. Infertility Females Based on findings from rats, REZUROCK may impair female fertility. The effect on fertility is reversible [see Nonclinical Toxicology (13.1) in the full prescribing information]. Males Based on findings from rats and dogs, REZUROCK may impair male fertility. The effects on fertility are reversible [see Nonclinical Toxicology (13.1) in the full prescribing information].
8.4 Pediatric Use
The safety and effectiveness of REZUROCK have been established in pediatric patients 12 years and older. Use of REZUROCK in this age group is supported by evidence from adequate and well-controlled studies of REZUROCK in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the pharmacokinetics of drug substance, that the exposure of drug substance is expected to be similar between adults and pediatric patients age 12 years and older, and that the course of disease is sufficiently similar in adult and pediatric patients to allow extrapolation of data in adults to pediatric patients. The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established.
8.5 Geriatric Use
Of the 186 patients with chronic GVHD in clinical studies of REZUROCK, 26% were 65 years and older. No clinically meaningful differences in safety or effectiveness of REZUROCK were observed in comparison to younger patients.
Active ingredient made in India. Distributed and marketed by:
Kadmon Pharmaceuticals, LLC
Warrendale, PA 15086 1-877-377-7862 REZUROCK™ is a trademark of Kadmon Pharmaceuticals, LLC. © 2021 Kadmon Pharmaceuticals, LLC, Warrendale, PA 15086. All rights reserved. KAD25000266 10/21
Expanding Biosimilars
continued from page 1
“Although there are still barriers to adoption across the board, momentum around biosimilars continues to accelerate, which can bring patients and the overall healthcare system expanded benefits through broader access to affordable lifesaving medications,” Dr. Oskouei said.
The U.S. biosimilars market has grown significantly since the FDA approved the first biosimilar, filgrastim-sndz (Zarxio, Sandoz), in 2015. Since then, the FDA has approved 35 biosimilars, 21 of which are commercially available, Dr. Oskouei said. The vast majority of those available (17) are provider-administered oncology therapies such as bevacizumabawwb (Mvasi, Amgen), rituximab-pvvr (Ruxience, Pfizer) and trastuzumab-dkst (Ogivri, Mylan-Biocon).
The U.S. biosimilars market will continue to grow and evolve over the coming years as more types of therapies become available and patient access increases, Dr. Oskouei said. Specifically, the approval last year of insulin glargineyfgn (Semglee, Viatris/Biocon)—the first interchangeable biosimilar that may be substituted for the reference product at the pharmacy without the intervention of the prescriber—means the U.S. market is entering a new phase of biosimilar activity, she said.
“The majority of the activity has been in the medical benefit space with healthcare provider–administered products,” she told Specialty Pharmacy Continuum. “The next wave will be focused on more products that enter the pharmacy benefit reimbursement model, so more selfinjectables and dispensing at retail, specialty sites of care and mail order. It’s a very exciting time.”
For example, seven adalimumab (Humira, AbbVie) biosimilars will become available in 2023, and another five are pending FDA approval. In addition, the number of biologics facing biosimilars competition will more than double by 2026, affecting mostly immunology and ophthalmology agents such as aflibercept (Eylea, Regeneron), etanercept (Enbrel, Amgen) and ustekinumab (Stelara, Janssen).
The Promise of Biosimilars
According to a 2021 report from the Association for Accessible Medicines, the aggregate savings from biosimilars could exceed $133 billion by 2025, a considerable increase from the $8 billion in savings attributed to biosimilars in 2020.
“That is the promise of biosimilars: They bring competition to some of those costly biologic treatment options, thereby lowering healthcare costs and enhancing patient accessibility and affordability to these treatments,” Dr. Oskouei said during her presentation.
However, perceptions of biosimilars vary among specialties, with more hesitation among prescribers in new therapeutic areas such as diabetes, ophthalmology and rheumatology, according to a survey of 115 retail pharmacists and more than 600 physicians conducted by Cardinal Health in 2021.
Much of that hesitation is driven by a lack of understanding of biosimilars’ efficacy and when to substitute a biosimilar for a reference product, the survey showed. For example, 42% of rheumatology prescribers and 32% of ophthalmology prescribers said they are likely to prescribe a biosimilar to new patients. However, only 11% and 32%, respectively, said they would switch a patient who is having success on a reference product.
Meanwhile, 67% of oncology prescribers said they would most likely subscribe a biosimilar to both new and existing patients, according to the survey data (Figure).
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Additional Resources
FDA educational resources for providers and patients
bit.ly/3yFYoDy
Cardinal Health biosimilars resources
“What is interesting to note is that the top concern is efficacy with biosimilars, which highlights the need to strengthen clinical confidence in these products with education efforts,” said Dr. Oskouei, who added that 71% of survey respondents said biosimilar education materials would be helpful in conversations with patients.
In addition, lack of payor adoption is also driving hesitancy regarding biosimilars, the survey showed. Among diabetes prescribers—which includes endocrinologists and primary care physicians—72% said they would utilize or prescribe biosimilars for existing patients whom payors have mandated a biosimilar (Figure).
“So, you can see as we get to that pharmacy benefit, self-injectable product–type, even the prescribers have a greater awareness that a lot of utilization is going to be dictated by managed care,” Dr. Oskouei said.
Despite this hesitation, pharmacists already support the growth of biosimilars through activities such as patient and clinical education, pharmacovigilance services, patient counseling, and cost-effectiveness analyses, she said.
This role will continue to grow as more biosimilars become available in more therapeutic areas and sites of care expand, including retail and specialty pharmacies and mail-order services, Dr. Oskouei said.
Pharmacists also are well positioned to help navigate the financial, clinical and operational considerations that will be necessary in successfully managing the growth of biosimilars, she said.
Cost will be a significant factor in the success of biosimilars, many of which will be outpatient administered or dispensed, Dr. Oskouei said.
Cash-paying, underinsured or uninsured patients will benefit from these low-cost alternatives, so “understanding patient access and reimbursement will be even more critical when these products come to market,” she said.
From a clinical standpoint, pharmacists can help drive patient and clinical understanding and acceptance through counseling and education, she said.
“Having proactive multi-stakeholder educational efforts are key. And this is truly multi-stakeholder from physicians, pharmacists, nurses and managed care stakeholders to really ensure that there’s awareness, comfort and confidence in these agents,” she said.
Pharmacists also will be instrumental in operationalizing interchangeable biosimilars, but they must work within the confines of each patient’s insurance requirements.
For example, if a patient gets a prescription for a brand-name biologic but their insurance plan prefers an interchangeable biosimilar, pharmacists will be in a position to automatically substitute to the biosimilar without obtaining a new prescription from the provider, Dr. Oskouei said. “So, there are some efficiencies there,” she said.
However, each state has different rules and regulations regarding interchangeability. “Some have different requirements when it comes to documentation, how long to keep records, who you communicate to and what time frame,” Dr. Oskouei said. “Understanding those state laws … is going to be important as these products continue to come to market.”
Pharmacists also should become active in supporting policies and policy reforms that can incentivize biosimilars and create competition among manufacturers, which will help further drive innovation, she said.
“By having a successful biosimilar market and lowering these healthcare costs, what we’re essentially doing is bringing the healthcare dollar to invest in the next generation of innovative treatments to improve even more patient outcomes and lives,” she said.
Increased Empowerment
“Although there are barriers to adoption across the board, momentum around biosimilars continues to accelerate, which can bring patients and the overall healthcare system expanded benefits through broader access to affordable, lifesaving medications,” Dr. Oskouei said.
And as biosimilars continue to grow—including an increase in retail interchangeable biosimilars—pharmacists will be called upon to help foster familiarity, confidence and acceptance among patients and providers.
“Pharmacists will be further empowered to support biosimilar adoption efforts and experiences,” Dr. Oskouei said. “Because of the expansion of pharmacists’ presence in these sites of care, pharmacists can continue to reach more patients.”
The aggregate savings from biosimilars could exceed
$133 billion
by 2025—a considerable increase from the
$8 billion
in savings attributed to biosimilars in 2020.
Source: Association for Accessible Medicines.
The sources reported no relevant financial disclosures.
Oncology prescribers n=373 Rheumatology prescribers n= 102 Ophthalmology prescribers n=102 Diabetes prescribers n=54
67% 67% 72%
42%
32% 42%
30%
27% 38%
35%
19%
11% 20%
5%
N/A N/A
New patients Existing patients having success on a reference product Existing patients having limited success on a reference product
Existing patients for whom payors have mandated a biosimilarb
25%
5% 7%
2%
I am not likely to prescribe a biosimilar for any patient at this time
Figure. For which patients are you most likely to prescribe a biosimilar?a
a Respondents asked to check all that apply. b This answer choice was not included in oncology and ophthalmology surveys. Source: 2022 Cardinal Health Biosimilars Report: the U.S. journey and path ahead. Cardinal Health. Published Feb 2022. www.cardinalhealth.com/en/product-solutions/pharmaceutical-products/biosimilars/ biosimilars-report.html
