Bristol Myers Squibb, announced that the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application (sNDA) to add positive data from the Phase 3 VALOR-HCM study to the U.S. Prescribing Information for CAMZYOS (mavacamten, 2.5 mg, 5 mg, 10 mg, 15 mg capsules). Data added to the label showed that treatment with CAMZYOS significantly reduced the composite endpoint of guideline-based eligibility for septal reduction therapy (SRT) at Week 16 or the decision to proceed with SRT prior to or at Week 16. This approval follows last year’s FDA approval of CAMZYOS, based on results from the Phase 3 EXPLORER-HCM trial, for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive HCM to improve functional capacity and symptoms.
“At Bristol Myers Squibb, we are committed to delivering innovative medicines to help improve the lives of patients living with serious diseases,” said Catherine Owen, Senior Vice President and General Manager, U.S. Commercial, Bristol Myers Squibb. “CAMZYOS is the first and only FDA-approved cardiac myosin inhibitor that specifically targets the underlying source of the disease and is redefining the treatment landscape for symptomatic NYHA class II–III obstructive HCM. Results from the Phase 3 VALOR-HCM study reinforce the data from the Phase 3 EXPLORER-HCM trial and further strengthen the clinical profile of CAMZYOS. We are proud to offer this important therapy to patients.”
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. 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. 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 moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors, and 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 the CAMZYOS REMS PROGRAM. Please see additional Important Safety Information including Boxed WARNING below. CAMZYOS is the first and only FDA-approved cardiac myosin inhibitor that specifically targets the underlying source of obstructive HCM.
Hypertrophic cardiomyopathy is the most commonly inherited heart disease, impacting between an estimated one in 200* and one in 500† people in the U.S. Obstructive HCM, which is the most common type of HCM and represents about two-thirds of all cases, is largely caused by dysfunction in the sarcomere which leads to a thickened heart muscle that obstructs or reduces blood flow from the heart to the rest of the body.1 Patients who are experiencing severe symptoms and have a dynamic LVOT gradient at rest or with provocation ≥ 50 mmHg, despite receiving the maximally tolerated medical therapy, may be eligible for SRT to reduce the thickness of the septal wall and alleviate obstruction.2
“SRT is an invasive surgical or catheter-based procedure and is typically available at comprehensive HCM treatment centers. In order to provide broader access to treatment for those patients whose obstructive HCM becomes so advanced that guidelines recommend SRT, more treatment options are needed,” said Anjali T. Owens, M.D., Medical Director of the Center for Inherited Cardiac Disease, Associate Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, and VALOR-HCM trial investigator and executive committee member BMS. “The VALOR-HCM study supports CAMZYOS as an oral treatment for obstructive HCM patients who are recommended for SRT.”
In the VALOR-HCM study, patients with symptomatic obstructive HCM (NYHA class III-IV or class II with exertional syncope or near syncope) who met the 2011 ACC/AHA Guideline criteria and were referred for SRT were randomized 1:1 to CAMZYOS (n=56) or placebo (n=56) for 16 weeks. At baseline, approximately 7% of the randomized patients were NYHA class II and 93% were NYHA class III+. The mean LVEF was 68%, and the mean post-exercise left ventricular outflow tract (LVOT) gradient was 84 mmHg. The baseline mean Kansas City Cardiomyopathy Questionaire-23 (KCCQ-23) Clinical Summary Score (CSS) was 68.
Results showed that CAMZYOS significantly reduced the primary composite endpoint of patient eligibility for SRT or the decision to proceed with SRT, with 82% of patients no longer eligible for the surgical procedure and deciding not to proceed with SRT after 16 weeks of treatment. Ten patients (18%) treated with CAMZYOS vs 43 patients (77%) in the placebo group decided to proceed with SRT prior to or at Week 16 or were SRT-eligible at Week 16; treatment difference (95% CI), 59% (44%, 74%); P<0.0001. Two patients (3.6%) in both the CAMZYOS and placebo groups decided to proceed with SRT prior to or at Week 16; 8 patients (14%) in the CAMZYOS group and 41 patients (74%) in the placebo group were SRT-eligible at Week 16.
Results also showed CAMZYOS met secondary endpoints (change from baseline to Week 16) vs the placebo group of:
- Mean post-exercise LVOT gradient (-39 mmHg for the CAMZYOS group vs -2 mmHg for the placebo group; difference [95% CI] of -38 mmHg [-49, -28], P<0.0001)
- Proportion with NYHA class improvement of at least 1 class (63% for the CAMZYOS group vs 21% for the placebo group; difference [95% CI] of 41% [25, 58], P<0.0001)
- KCCQ-23 CSS**, mean (+10 points for the CAMZYOS group vs +2 points for the placebo group; difference [95% CI] of 9 points [5, 14], P<0.0001)
- Mean change in baseline in KCCQ-23 Total Symptom Score (TSS) (+10 vs +2)
- Mean change in baseline in KCCQ-23 Physical Limitations (PL) (+10 vs +2)
**The Kansas City Cardiomyopathy Questionaire-23 Clinical Summary Score (KCCQ‑23 CSS) is derived from the Total Symptom Score (TSS) and the Physical Limitations (PL) score of the KCCQ‑23. The CSS ranges from 0 to 100 with higher scores representing less severe symptoms and/or physical limitations.
There were no new adverse reactions identified in VALOR-HCM. 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.
SOURCE: BusinessWire