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ph-1180

Camzyos (mavacamten) Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-1180

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
10-01-2024

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Camzyos® (mavacamten) Capsule	Treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms		1

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

HCM

Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease reported in populations globally. Inherited in an autosomal dominant pattern, the distribution is equal by sex, although women are diagnosed less commonly than men. The prevalence of unexplained asymptomatic hypertrophy in young adults in the United States has been reported to range from 1:200 to 1:500. Symptomatic hypertrophy based on medical claims data has been estimated at <1:3000 adults in the United States; however, the true burden is much higher when unrecognized disease in the general population is considered. Clinical evaluation for HCM may be triggered by occurrence of symptoms, a cardiac event, detection of a heart murmur, an abnormal 12-lead electrocardiogram (ECG) identified on routine examinations, or through cardiac imaging during family screening studies.(2)

Efficacy

Mavacamten is a reversible inhibitor selective for cardiac myosin. Mavacamten modulates the number of myosin heads that can enter “on actin” (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. In HCM patients, myosin inhibition with mavacamten reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures.(1)

The efficacy of Camzyos was evaluated in EXPLORER-HCM, a phase 3, double-blind, randomized, placebo-controlled, multicenter, international, parallel group trial in 251 adults with symptomatic NYHA class II and III obstructive HCM, LVEF greater than or equal to 55%, and Valsalva LVOT peak gradient greater than or equal to 50 mmHg at rest or with provocation. Patients on dual therapy with beta blocker and calcium channel blocker treatment or monotherapy with disopyramide or ranolazine were excluded. Patients with a known infiltrative or storage disorder causing cardiac hypertrophy that mimicked obstructive HCM, such as Fabry disease, amyloidosis, or Noonan syndrome with left ventricular hypertrophy, were also excluded. Patients were randomized in a 1:1 ratio to receive either a starting dose of 5 mg of Camzyos or placebo once daily for 30 weeks. Treatment assignment was stratified by baseline disease severity NYHA functional class, baseline use of beta blockers, and type of ergometer (treadmill or exercise bicycle). Groups were well matched with respect to age (mean 59 years), BMI (mean 30 kg/m), heart rate (mean 62 bpm), blood pressure (mean 128/76 mmHg), and race (90% Caucasian). Males comprised 54% of the Camzyos group and 65% of the placebo group. At baseline, approximately 73% of the randomized patients were NYHA class II and 27% were NYHA class III. The mean LVEF was 74%, and the mean Valsalva LVOT gradient was 73 mmHg. About 10% had prior septal reduction therapy, 75% were on beta 2 blockers, 17% were on calcium channel blockers, and 14% had a history of atrial fibrillation. All patients were initiated on Camzyos 5 mg (or matching placebo) once daily, and the dose was periodically adjusted to optimize patient response (decrease in LVOT gradient with Valsalva maneuver) and maintain LVEF greater to or equal to 50%. The primary composite functional endpoint, assessed at 30 weeks, was defined as the proportion of patients who achieved either improvement of mixed peak oxygen consumption (pVO2) by greater than or equal to 1.5 mL/kg/min plus improvement in NYHA class by at least 1 or improvement of pVO2 by greater than or equal to 3.0 mL/kg/min plus no worsening in NYHA class. A greater proportion of patients met the primary endpoint at Week 30 in the Camzyos group compared to the placebo group (37% vs. 17%, respectively, p=0.0005).(1)

Safety

Camzyos has a boxed warning for the risk of heart failure. Camzyos reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction.(1)

Echocardiogram assessments of LVEF are required prior to and during treatment with Camzyos. Initiation of Camzyos in patients with LVEF <55% is not recommended. Interrupt Camzyos if LVEF is <50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status.(1)

Concomitant use of Camzyos with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction; therefore, the use of Camzyos is contraindicated with the following:(1)

Moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors
Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers

Because of the risk of heart failure due to systolic dysfunction, Camzyos is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Camzyos REMS Program.(1)

REFERENCES

Number	Reference
1	Camzyos prescribing information. Bristol Meyers Squibb. June 2023.
2	Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients with Hypertrophic Cardiomyopathy. Circulation (New York, NY). 2020;142(25). doi:10.1161/cir.0000000000000937

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)	Target Generic Agent(s)	Strength	Targeted MSC	Available MSC	Final Age Limit	Preferred Status

Camzyos	mavacamten cap	10 MG ; 15 MG ; 2.5 MG ; 5 MG	M ; N ; O ; Y	N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	QL Amount	Dose Form	Day Supply	Duration	Addtl QL Info	Allowed Exceptions	Targeted NDCs When Exclusions Exist

Camzyos	Mavacamten Cap	2.5 MG	30	Capsules	30	DAYS
Camzyos	Mavacamten Cap	5 MG	30	Capsules	30	DAYS
Camzyos	Mavacamten Cap	10 MG	30	Capsules	30	DAYS
Camzyos	Mavacamten Cap	15 MG	30	Capsules	30	DAYS

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Camzyos	mavacamten cap	10 MG ; 15 MG ; 2.5 MG ; 5 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Camzyos	Mavacamten Cap	5 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Camzyos	Mavacamten Cap	2.5 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Camzyos	Mavacamten Cap	15 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Camzyos	Mavacamten Cap	10 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
PA	Initial Evaluation Target Agent(s) will be approved when ALL of the following are met: ONE of the following: The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR The patient has a diagnosis of symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) AND ALL of the following: The patient has a left ventricular ejection fraction (LVEF) of greater than or equal to 55% AND The patient has a left ventricular outflow tract (LVOT) peak gradient greater than or equal to 50 mmHg at rest or with provocation (Valsalva or post-exercise) AND The patient does not have a known infiltrative or storage disorder causing cardiac hypertrophy that mimics obstructive HCM (e.g., Fabry disease, amyloidosis, Noonan syndrome with left ventricular hypertrophy) AND ONE of the following: The patient has tried and had an inadequate response to a beta blocker OR The patient has an intolerance or hypersensitivity to therapy with beta blockers OR The patient has an FDA labeled contraindication to ALL beta blockers AND ONE of the following The patient has tried and had an inadequate response to a calcium channel blocker OR The patient has an intolerance or hypersensitivity to therapy with calcium channel blockers OR The patient has an FDA labeled contraindication to ALL calcium channel blockers OR The patient has another FDA labeled indication for the requested agent and route of administration AND ONE of the following: The patient’s age is within FDA labeling for the requested indication for the requested agent OR There is support for using the requested agent for the patient’s age for the requested indication AND The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met: The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND The patient has had clinical benefit with the requested agent AND The patient has a left ventricular ejection fraction (LVEF) of greater than or equal to 50% AND The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Module

Clinical Criteria for Approval

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

ONE of the following:
1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
3. The patient has a diagnosis of symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) AND ALL of the following:
  1. The patient has a left ventricular ejection fraction (LVEF) of greater than or equal to 55% AND
  2. The patient has a left ventricular outflow tract (LVOT) peak gradient greater than or equal to 50 mmHg at rest or with provocation (Valsalva or post-exercise) AND
  3. The patient does not have a known infiltrative or storage disorder causing cardiac hypertrophy that mimics obstructive HCM (e.g., Fabry disease, amyloidosis, Noonan syndrome with left ventricular hypertrophy) AND
  4. ONE of the following:
    1. The patient has tried and had an inadequate response to a beta blocker OR
    2. The patient has an intolerance or hypersensitivity to therapy with beta blockers OR
    3. The patient has an FDA labeled contraindication to ALL beta blockers AND
  5. ONE of the following
    1. The patient has tried and had an inadequate response to a calcium channel blocker OR
    2. The patient has an intolerance or hypersensitivity to therapy with calcium channel blockers OR
    3. The patient has an FDA labeled contraindication to ALL calcium channel blockers OR
4. The patient has another FDA labeled indication for the requested agent and route of administration AND
ONE of the following:
1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
2. There is support for using the requested agent for the patient’s age for the requested indication AND
The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
The patient has had clinical benefit with the requested agent AND
The patient has a left ventricular ejection fraction (LVEF) of greater than or equal to 50% AND
The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
QL with PA	Quantity limit for the Target Agent(s) will be approved when ONE of the following is met: The requested quantity (dose) does NOT exceed the program quantity limit OR The requested quantity (dose) exceeds the program quantity limit AND ONE of the following: BOTH of the following: The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND There is support for therapy with a higher dose for the requested indication OR BOTH of the following: The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR BOTH of the following: The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND There is support for therapy with a higher dose for the requested indication Length of Approval: up to 12 months

Module

Clinical Criteria for Approval

QL with PA

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

The requested quantity (dose) does NOT exceed the program quantity limit OR
The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
1. BOTH of the following:
  1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
  2. There is support for therapy with a higher dose for the requested indication OR
2. BOTH of the following:
  1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
  2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
3. BOTH of the following:
  1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
  2. There is support for therapy with a higher dose for the requested indication

Length of Approval: up to 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

Commercial _ PS _ Camzyos_PAQL _ProgSum_ 10-01-2024