Bristol Myers Squibb received approval from the U.S. FDA for Camzyos (mavacamten, 2.5 mg, 5 mg, 10 mg, 15 mg capsules) for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (obstructive HCM) to improve functional capacity and symptoms. Camzyos is the first and only FDA-approved allosteric and reversible inhibitor selective for cardiac myosin that targets the underlying pathophysiology of obstructive HCM. Bristol Myers has forecast the drug reaching $4 billion in sales by 2029.

The full U.S. Prescribing Information for Camzyos includes 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. Monitoring is required. 

This approval is based on data from the Phase 3 EXPLORER-HCM trial. 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 left ventricular outflow tract (LVOT) gradient was 73 mmHg. At Week 30, 37% (n=45/123) of patients taking Camzyos achieved the primary endpoint, defined as the proportion of patients who achieved either improvement of mixed venous oxygen tension plus improvement in NYHA class, plus no worsening in NYHA class, versus 17% (n=22/128) treated with placebo.

Additionally at Week 30, patients receiving Camzyos had greater improvement compared to placebo group across all secondary endpoints: Mean change from baseline post-exercise LVOT peak gradient; Mean change from baseline in pVO2; Number of patients with improvement of NYHA class ≥ 1; Mean change from baseline in KCCQ-23 † CSS; Mean change in baseline in KCCQ-23 Total Symptom Score (TSS) (12 vs 5); and Mean change in baseline in KCCQ-23 Physical Limitations (PL) (15 vs 4).

In the EXPLORER-HCM trial, adverse reactions occurring in >5% of patients and more commonly in the Camzyos group than in the placebo group were dizziness (27% vs 18%) and syncope (6% vs 2%). Mean (SD) resting LVEF was 74% (6) at baseline in both treatment groups. Mean (SD) absolute change from baseline in LVEF was -4% (8) in the Camzyos group and 0% (7) in the placebo group over the 30-week treatment period. At Week 38, following an 8-week interruption of trial drug, mean LVEF was similar to baseline for both treatment groups. Additionally, 7 (6%) patients in the Camzyos group and 2 (2%) patients in the placebo group experienced reversible reductions in LVEF to <50% (median 48%: range 35-49%) while on treatment. In all 7 patients treated with Camzyos, LVEF recovered following interruption of Camzyos.