Regulatory Decision Summary for Camzyos

This Supplement to a New Drug Submission was filed by Bristol-Myers Squibb Canada to obtain market authorization pursuant to section C.08.004 of the Food and Drugs Regulations to revise the indication for Camzyos (mavacamten) to include that the drug reduces the need for Septal Reduction Therapy (SRT) in adult patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Following review, a revised indication was not considered necessary as the initially authorized indication includes the patient population requested in this submission.

In the current Supplement to a New Drug Submission, the Sponsor submitted a new randomized, double-blind, placebo-controlled, Phase 3 study (VALOR-HCM) in adult patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) to expand the efficacy and safety knowledge of Camzyos. All patients in VALOR-HCM had to qualify for septal reduction therapy (SRT) and could be included if using disopyramide or other concomitant medications related to oHCM. The majority of patients were classified as d New York Heart Association (NYHA) Class III (92%). In VALOR-HCM, of the 112 recruited adults with symptomatic oHCM, 56 patients were treated with Camzyos 2.5 - 15 milligrams (mg) daily and 55 were treated with placebo. The starting dose was 5 mg which could be periodically adjusted to a maximum of 15 mg to optimize the patient’s therapeutic response. The initial placebo-controlled trial had a median duration of exposure of 17 weeks (range: 3-19 weeks).

Camzyos was shown to be superior to placebo in reducing the proportion of patients who met the primary endpoint (18% vs. 77% for Camzyos and placebo, respectively), a composite of decision to proceed with SRT prior to or at Week 16 or who were eligible for SRT (left ventricular outflow tract gradient of greater than or equal to 50 mmHg and NYHA class III-IV, or class II with exertional syncope or near syncope) at Week 16. The treatment difference (95% Confidence Interval) was 59% (44, 74), p<0.0001. The composite endpoint was met because, at Week 16, 14% of patients who received Camzyos remained SRT eligible compared to 70% in the placebo group. Two patients in each group decided to proceed with SRT.

The most commonly reported adverse events (greater than or equal to 5% of patients) observed at higher frequency in the Camzyos group compared to placebo included fatigue (8.9% vs. 3.6% for Camzyos and placebo, respectively), dizziness (7.1% vs. 5.5%), nausea (7.1% vs. 1.8%), dyspnea (7.1% vs. 5.5%), rash (7.1% vs. 0%), atrial fibrillation (7.1% vs. 0%), urinary tract infection (5.4% vs. 1.8%), and hypertension (5.4% vs. 3.6%). Safety was generally consistent with current knowledge of the adverse events and laboratory findings associated with the mode of action of Camzyos and the underlying oHCM condition.

After the initial placebo-controlled 16-week period, VALOR-HCM included a long-term extension phase where 108 oHCM patients who completed the initial placebo-controlled period all received Camzyos. No patients that previously received 16 weeks of Camzyos had cardiac failure. Two patients in the previous placebo group who received Camzyos in the long-term extension phase had left ventricular ejection fraction below 30%. Overall, no new safety signals with Camzyos treatment were observed from the VALOR-HCM study.

Based on the allowed background therapies in the VALOR-HCM trial, more than ninety percent of patients were taking at least one concomitant medication related to oHCM, twenty patients (33%) were on combination of a beta-blocker, calcium channel blocker and/or disopyramide. Due to limited clinical experience, the safety of concomitant use of Camzyos with disopyramide, or use of Camzyos in patients taking beta blockers in combination with a calcium channel blocker has not been fully established. As a result, cautionary statements and risk minimization measures were implemented in the Product Monograph. Following review, a revised indication was not considered necessary as the initially authorized indication includes the patient population requested in this submission.

A Risk Management Plan (RMP) for Camzyos was reviewed by Health Canada and considered acceptable. Camzyos will continue to be monitored post market as outlined in the RMP, with routine and non-routine pharmacovigilance activities.

Overall, the benefit-harm-uncertainty profile is favourable for Camzyos for the currently authorized indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) pursuant to section C.08.004 of the Food and Drug Regulations was recommended.

For further details about Camzyos, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.