dm+d

Unassigned

New Medicines

CamzyosObstructive hypertrophic cardiomyopathy

Information

Camzyos
New molecular entity
Bristol-Myers Squibb
Bristol-Myers Squibb

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Launched
Yes
Oct 22FDA accepts a supplemental new drug application (sNDA) for Camzyos for an expanded indication to reduce the need for septal reduction therapy (SRT). CAMYZOS is currently FDA approved to improve functional capacity and symptoms. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 16, 2023. The sNDA submission is based on the results of the PIII VALOR-HCM study [22].
Apr 22Mavacamten application is still under review by the CHMP [21]
Apr 22BMS announce FDA has approved mavacamten for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms [20]
Nov 21A decision from FDA has been delayed to April 22 as the FDA need more time to consider an update to the Risk Evaluation Mitigation Strategy program [16].
Oct 21EMA has validated Marketing Authorization Application (MAA) for mavacamten. Validation of the application confirms the submission is complete, and the EMA’s centralized procedure with Committee for Medicinal Products for Human Use (​CHMP)’s assessment begins. [14]
May 21A FDA decision is expected in Jan 22 [13].
Mar 21The FDA has accepted a New Drug Applicationfor mavacamten for patients with symptomatic obstructive hypertrophic cardiomyopathy [11].
Dec 20Bristol Myers-Squibb is now developing mavacamten. Filings will be supported by data from the EXPLORER-HCM trial [10].
Jul 20Granted Breakthrough therapy Designation in US [7].
May 20U.S. Regulatory Submission Planned for Early 2021 [6].
Sep 19Sanofi announced in its Q3 Pipeline Movements that development of mavacamten for obstructive hypertrophic cardiomyopathy has been discontinued [5].
Oct 18Has orphan drug status in US [4].
Sep 18PIII development starts [2].

Category

Myosin inhibitor that reduces excessive cardiac muscle contractility
Hypertrophic cardiomyopathy has an estimated adult prevalence of 1 in 500, with left and/or right ventricular hypertrophy [19].
Obstructive hypertrophic cardiomyopathy
Oral

Further information

Yes

Trial or other data

Oct 22Currently, it is recommended that many patients with severe symptomatic obstructive hypertrophic cardiomyopathy undergo SRT. This often requires either an open-heart surgical procedure or septal ablation procedure – both specialised care options. The PIII VALOR-HCM study was a randomised, double-blind, placebo-controlled study, which evaluated Camzyos in patients with symptomatic, obstructive HCM (NYHA class III-IV) who met the 2011 ACC/AHA guideline criteria for SRT and who have been referred for an invasive procedure. In addition to meeting its primary, Camzyos met all secondary endpoints with a high degree of statistical significance, with no new safety signals [22].
Apr 22Interim data of the EXPLORER-LTE cohort from the long term safety extension study NCT03723655 of mavacamten in adults who completed EXPLORER-HCM showed sustained improvement in left ventricular outflow tract gradients, NYHA Class and N-terminal pro brain natriuretic peptide levels (n=231). At 48 and 84 weeks, mavacamten safety was consistent with that seen in the EXPLORER-HCM study. Primary estimated completion date= Sep 2025 [18]
Feb 22 BMS announce positive topline results from PIII VALOR-HCM Trial in >100 adults eligible for SRT. Trial met its primary endpoint (composite of number of patients who decide to proceed with SRT prior to or at week 16 & number who remain SRT-guideline eligible at week 16) [17].
Nov 21Data from the beta-blocker subgroup of the EXPLORER trial showed that mavacamten benefited patients regardless of whether they were on common treatments [15].
May 21PIII EXPLORER-HCM (NCT03470545; n=251) is published in the Lancet; mavacamten improved health status, with greater change in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) score vs placebo at 30 weeks (mean 14.9 vs 5.4; p<00001) and NNT of 5 (95% CI 3–11) for marked improvement. Gains returned to baseline after treatment stopped [12].
Sep 20NCT03470545 RCT (n=251) reported improved exercise capacity, LVOT obstruction, NYHA functional class, and health status, with 45 [37%] of 123 patients on mavacamten meeting primary endpoint versus 22 [17%] of 128 on placebo (p=0·0005) [8].
Aug 20PIII VALOR-HCM clinical trial starts. This will enrol individuals with obstructive hypertrophic cardiomyopathy (HCM) who have been referred for septal reduction therapy (SRT) and are refractory to current therapeutic options, including those who have severe symptoms (NYHA Class IV) [8].
May 20PIII trial EXPLORER-HCM trial results (NCT03470545) found the primary and all secondary endpoints of the EXPLORER trial were met with statistical significance (p≤0.0006 for all endpoints. Mavacamten was well tolerated, and meaningful improvements in symptoms, functional status and quality of life, as well as reduction or elimination in obstruction of the left ventricle, were observed [6].
Jun 18PIII EXPLORER-HCM trial to evaluate mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy starts (NCT03470545). 220 patients will be recruited in the US. Primary outcome is percentage of patients achieving a clinical response at 30 weeks, defined as having an improvement in symptom severity from baseline as assessed by New York Heart Association (NYHA) functional classification (e.g. I, II, III, or IV) and increase in exercise capacity from baseline to Week 30 as assessed by measurement of peak oxygen consumption (pVO2) (e.g. mL/min/kg) determined by cardiopulmonary exercise testing (CPET). Collection of these data is due to complete Jun 20 [3].

Evidence based evaluations