Bristol Myers Squibb's New Drug Application for Mavacamten in Obstructive Hypertrophic Cardiomyopathy Accepted by FDA
Mar 19, 2021 23:50
CST Updated
Mar 20, 23:50
Bristol-Myers Squibb
Biopharmaceutical and Nutritional Product R&D and Sales
FDA
U.S. Food and Drug Administration
March 19, 2021 /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for mavacamten, a novel, oral, allosteric modulator of cardiac myosin, for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), a chronic heart disease with high prevalence.FDAThe PDUFA goal date has been set for January 28, 2022.
Mavacamten is a first-in-class, oral, allosteric inhibitor of cardiac myosin, indicated for the treatment of diseases whose underlying causes are hypercontractility and impaired diastolic filling of the heart. Mavacamten is believed to reduce myocardial contractility by inhibiting the formation of excessive myosin-actin cross-bridges. Excessive formation of myosin-actin cross-bridges can lead to hypercontractility, left ventricular hypertrophy, and reduced compliance. In clinical and preclinical studies, mavacamten has consistently demonstrated reductions in wall stressBiomarkers, reduce excessive myocardial contraction, and increase diastolic compliance.
In July 2020, the United StatesFDABreakthrough Therapy Designation was granted to mavacamten for the treatment of oHCM. Mavacamten was initially developed for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Based on its mechanism of action and evidence of therapeutic activity, mavacamten is also being clinically investigated for the treatment of symptomatic non-obstructive hypertrophic cardiomyopathy (HCM) and heart failure with preserved ejection fraction (HFpEF).
Hypertrophic Cardiomyopathy (Image source: urmc.rochester.edu)
The submission of the New Drug Application (NDA) for mavacamten was based on the results of the pivotal Phase 3 EXPLORER-HCM trial. This trial was conducted in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) and compared mavacamten with placebo. The trial results demonstrated that mavacamten exhibited robust therapeutic efficacy, yielding clinically meaningful improvements in symptoms, functional status, and quality of life, while also demonstrating the ability to alleviate left ventricular outflow tract obstruction. In the EXPLORER-HCM study, all primary and secondary endpoints achieved statistical significance.
Roland Chen, M.D., Senior Vice President of Cardiovascular Development at Bristol-Myers Squibb, stated, “HCM is the most commonHeredityValvular heart disease is a chronic, debilitating, and progressive condition. Patients may experience symptoms such as shortness of breath, dizziness, and fatigue, as well as severe, life-altering complications, including heart failure and arrhythmias.Strokeand sudden cardiac death. Today’s FDA acceptance of the NDA for mavacamten brings us one step closer to providing a highly targeted therapy for patients with obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten is a first-in-class myosin inhibitor that addresses the underlying molecular defect of this disease. We are committed to supporting the treatment of patients with HCM and look forward to working withFDAcooperation.”
Chemical Structure of Mavacamten (Image Source: chemsrc.com)
Mavacamten (MYK-461) was developed by MyoKardia. On October 5, 2020, Bristol-Myers Squibb announced the acquisition of MyoKardia for $13.1 billion in cash, representing a 60% premium. On November 17, 2020, Bristol-Myers Squibb announced that the acquisition of MyoKardia had been successfully completed. This acquisition was Bristol-Myers Squibb’s second-largest transaction, following its $74 billion acquisition of Celgene in 2019.
Notably, on August 11, 2020, byInvestment CompanyLianBio, incubated by Perceptive Advisors, was officially established and announced two significant partnerships on the same day: one to introduce BridgeBio Pharma’s product pipeline into China, and the other to introduce MyoKardia’s Mavecamten into China.
Bristol-Myers Squibb has high hopes for mavacamten. Upon acquiring MyoKardia, the company declared that mavacamten would become a first-in-class drug for the treatment of hypertrophic cardiomyopathy (HCM). The industry is also very optimistic about the commercial prospects of mavacamten. In December 2020, the pharmaceutical market research firm Evaluate Vantage released its “Top 10 New Drugs with the Greatest Commercial Potential in 2021,” in which mavacamten ranked third. Evaluate Vantage projected thatMavacamten’s global sales are projected to reach $2 billion in 2026.. (Bioon.com)