Variation in payer coverage of mavacamten (Camzyos) for hypertrophic cardiomyopathy: one year post approval

Date: August 9, 2023

Molly T. Beinfeld, MPH, Dan Enright, MS and Jason H. Wasfy, MD, MS, MPhil

In a significant milestone for patients with hypertrophic cardiomyopathy (HCM), the US Food and Drug Administration (FDA) approved mavacamten (Camzyos®, Bristol Myers Squibb™), a first-in-class cardiac myosin inhibitor, in April 2022.¹ We examined US payer coverage of mavacamten one year after its approval and found significant variation in payers’ step therapy protocols, approval durations, and reauthorization criteria. In this blog, we discuss the implications of these findings for patients, and for next generation myosin inhibitors.

What is HCM?

HCM is a genetic heart condition that causes thickening of the heart muscle, resulting in shortness of breath, chest pain, and in rare instances, sudden cardiac death. While there is no cure, medications such as beta blockers and calcium channel blockers can help improve quality of life and reduce the risk of complications, however there are important side effects and contraindications. Septal reduction procedures, such as percutaneous alcohol septal ablation and surgical myectomy have risks that many patients would choose to avoid.²

What is mavacamten?

Mavacamten has been shown to improve function and symptoms of HCM beyond existing treatments in the short term, based on data from the EXPLORER-HCM trial.³ The VALOR-HCM trial also showed that mavacamten can reduce or delay the need for septal reduction therapy (myectomy or ablation)⁴, but longer term data are needed. The FDA approved mavacamten for patients with obstructive HCM and New York Heart Association (NYHA) class II-III symptoms and includes a black box warning for risk of heart failure.⁵

Given the evolving evidence on mavacamten and high costs of the drug (estimated to be roughly $90k per year per SSR Health), the question remains: how do commercial health plans cover mavacamten? What sources are health plans using to guide coverage? What are the implications for next generation myosin inhibitors?

How do health plans cover mavacamten?

Coverage polices reflect a complex set of inputs and health plans serve different populations. We can examine how health plans cover mavacamten by summarizing two utilization management tools that may limit access to the drug by patients indicated for treatment by the FDA:

• Clinical requirements, which specify the clinical criteria patients must satisfy, such as symptom severity or duration; and
• Step-therapy protocols, which require patients to first try one or more alternative treatments and experience treatment failure before they can receive mavacamten.

Our data come from the Tufts-CEVR Specialty Drug Evidence and Coverage (SPEC) Database, which contains detailed information on how 18 large US commercial health plans cover specialty drugs and products.

As of April, 2023, coverage policies were available for 13 commercial health plans for mavacamten in SPEC. Twelve of the 13 plans with available coverage policies imposed restrictions that limit access to mavacamten beyond the FDA indication (Table 1).

Clinical restrictions

Seven plans required confirmation of diagnosis without any specific requirements, while 6 required left ventricular wall thickness ≥ 15mm OR ≥ 13mm with familial HCM confirmed by genetic tests. Twelve plans required patients to have a left ventricular ejection fraction (LVEF) of ≥ 55%, and 9 plans had the additional requirement of Valsalva left ventricular outflow tract (LVOT) peak gradient ≥ 50 mmHg at rest or with provocation. One plan also required resting oxygen saturation ≥ 90%.

All of these clinical restrictions correspond to the eligibility requirements in mavacamten’s FDA registration study, EXPLORER-HCM.³

All 13 plans required documentation in the form of chart notes or medical records confirming diagnosis and baseline testing to confirm disease severity. In cases of familial HCM, plans further required documentation of positive genetic tests. These requirements of genetic testing will likely create unnecessary barriers to care as well as unnecessary costs. Although the diagnosis of HCM is subtle and sometimes requires confirmation through genetic testing, candidacy for mavacamten is not likely to be related to confirmation of an inherited cardiomyopathy.

Step therapy protocols

Two plans imposed no step therapy protocols in their mavacamten coverage policies, while nine required an inadequate response, intolerance, or contraindication to beta blockers and/or calcium channel blockers. Two plans required a step through all of the following: beta blockers, calcium channel blockers, and disopyramide. The comparative effectiveness of mavacamten versus disopyramide is a prominent evidence gap. There also have been shortages of the long-acting form of disopyramide, which will create barriers to patients and clinicians with step therapy requirements for disopyramide.

Approval duration and reauthorization requirements

Duration of initial approval varied across plans, from 3 to 12 months. One year was the most common approval duration (5 plans), followed by 6 months (4 plans). Reauthorization requirements were included in all but one coverage policy. Eleven payers required some demonstration of clinical benefit (variably defined), and one required no worsening of symptoms. Reauthorization approval duration was 12 months for all payers.

What are the implications for next generation myosin inhibitors?

Plans have imposed coverage restrictions on mavacamten, likely because of the treatment’s high price, uncertain long-term benefits and unfavorable cost-effectiveness. As newer generation myosin inhibitors (such as aficamten, which the FDA designated as a breakthrough therapy) come to market, they will likely face similar barriers to access.

Clinical criteria

As is the case of mavacamten, we expect at least some plans’ aficamten coverage policies to impose clinical criteria that correspond to aficamten registration trial’s eligibility criteria. That is, plans may require patients to have been diagnosed with HCM with left ventricular wall thickness ≥ 15mm or ≥ 13mm in familial HCM, post-Valsalva LVOT ≥ 50 mmHg at baseline AND LVEF ≥ 60%.⁶ It is likely that clinical coverage requirements for aficamten will vary across plans, just as they do for mavacamten.

Step therapy

We expect coverage policy step therapy requirements for aficamten to be largely consistent with the corresponding coverage requirements for mavacamten in that they may require patients to first try beta blockers and/or calcium channel blockers. It is unlikely that plans will require patients to step through mavacamten to access aficamten, but step requirements will likely vary across plans.

Summary of findings

Our analysis found variation in how health plans cover mavacamten. Plans were largely consistent in application of prior authorization requirements for diagnosis confirmation and disease severity, which aligned with the eligibility criteria for mavacamten’s registration study. However, plans varied in application of step therapy protocols: mavacamten could be first, second, third, or fourth line of therapy depending on the plan. Most plans required prescribing by or in consultation with a cardiologist and documentation such as medical records or chart notes confirming diagnosis, baseline echocardiogram, and genetic tests, if applicable. Approval duration varied from 3 to 12 months and almost all payers required some demonstration of clinical benefit for reauthorization.

Consistency of coverage with ICER recommendations

In its 2021 assessment of HCM treatments, the Institute for Clinical and Economic Review (ICER) suggested the following policy recommendations:

• Payers should use the FDA label as the guide to coverage and use the clinical eligibility criteria from the drug’s registration study to define target subgroups of patients
• Genetic testing should not be required to confirm diagnosis prior to approval of mavacamten
• Initial authorization should be long enough to establish documented benefits
• Mavacamten should be prescribed by providers with expertise in managing the condition
• It is reasonable to require steps through beta blockers and calcium channel blockers but not to require septal reduction therapies or disopyramide⁷

Most payers covered mavacamten in a manner consistent with the ICER recommendations, although two coverage policies included an additional step through disopyramide. These differences can be problematic for patient access and clinical decision making since drug coverage varies with health insurance plans. Health plans appear to be covering mavacamten for patients that match the eligibility requirements of the registration study. Next generation myosin inhibitors will likely face similar barriers to access.

More on the Specialty Drug Evidence and Coverage (SPEC) Database

The Specialty Drug Evidence and Coverage (SPEC) Database is a first-of-its-kind resource designed to enhance the transparency of commercial health plan specialty drug coverage. SPEC draws on publicly available medical and pharmacy coverage policies issued by 18 of the largest commercial health plans. Health plans in SPEC cover roughly 170 million lives, or 70% of the market. SPEC includes 399 drugs manufactured by 105 different pharmaceutical and biotech companies. We keep SPEC timely by updating its contents every four months. SPEC includes information on three principal components: (1) health plan coverage decisions, (2) the evidence health plans cite in their coverage policies, and (3) specialty drug attributes.

Access to SPEC is through the CEVR Sponsorship program. Access to the online search portal of the SPEC database is also available for individuals from academic organizations for non-commercial use of the data. Contact James Chambers (jchambers@tuftsmedicalcenter.org) for more information.

References

1. https://www.fda.gov/drugs/news...
2. Maron BJ, Desai MY, Nishimura RA, Spirito P, Rakowski H, Towbin JA, Rowin EJ, Maron MS, Sherrid MV. Diagnosis and Evaluation of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022 Feb 1;79(4):372-389. doi: 10.1016/j.jacc.2021.12.002. PMID: 35086660.
3. Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, Saberi S, Lakdawala NK, Wheeler MT, Owens A, Kubanek M, Wojakowski W, Jensen MK, Gimeno-Blanes J, Afshar K, Myers J, Hegde SM, Solomon SD, Sehnert AJ, Zhang D, Li W, Bhattacharya M, Edelberg JM, Waldman CB, Lester SJ, Wang A, Ho CY, Jacoby D; EXPLORER-HCM study investigators. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020 Sep 12;396(10253):759-769. doi: 10.1016/S0140-6736(20)31792-X. Epub 2020 Aug 29. Erratum in: Lancet. 2020 Sep 12;396(10253):758. PMID: 32871100.
4. Desai MY, Owens A, Geske JB, Wolski K, Saberi S, Wang A, Sherrid M, Cremer PC, Naidu SS, Smedira NG, Schaff H, McErlean E, Sewell C, Balasubramanyam A, Lampl K, Sehnert AJ, Nissen SE. Dose-Blinded Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy: Outcomes Through 32 Weeks. Circulation. 2023 Mar 14;147(11):850-863. doi: 10.1161/CIRCULATIONAHA.122.062534. Epub 2022 Nov 6. PMID: 36335531.
5. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214998s000lbl.pdf
6. https://www.clinicaltrials.gov/study/NCT0576734
7. https://icer.org/wp-content/up...

Table 1. Variation in US Commercial Health Plan Coverage of Mavacamten, April 2023