At long last, there is a FDA approved drug specifically intended for the treatment of hypertrophic cardiomyopathy. After several years of testing, and based on the results of the groundbreaking EXPLORER-HCM trial, Bristol Myers Squibb’s new drug mavacamten, being marketed under the brand name Camzyos, is now available to HCM patients.
In addition to the presentation of the results of the VALOR-HCM study which compared mavacamten to septal reduction techniques, covered here in its own HCMBeat blog entry, ACC 2022 featured two other presentations about the new class of drugs known as myosin inhibitors, such as Bristol Myers Squibb’s mavacamten and Cytokinetics’ aficamten.
The Phase 3 VALOR-HCM trial results were presented this morning at the American College of Cardiology annual meeting in Washington, DC by the principal investigator, Dr. Milind Desai of the Cleveland Clinic, and the results are good!
What was the VALOR-HCM study?
15 – 20 million people worldwide are estimated to have HCM, with 2/3 of this group having the obstructive form which can cause severe symptoms. Historically, these patients have been treated with medications approved for other conditions, and if those don’t relieve symptoms, they are referred on for septal reduction therapies (SRT) like alcohol septal ablation (a catheter based procedure) or septal myectomy (open heart surgery), which are invasive therapies requiring specialized care and which are not widely available.
The VALOR study was designed to compare mavacamten head to head with SRT to see if mavacamten could be a non-invasive treatment alternative for obstructive HCM.
The U.S. Food and Drug Administration (FDA) has postponed the date by which it must complete its review of mavacamten – the first drug made specifically to treat HCM. The FDA was originally scheduled to announce its decision in late January 2022, but that date has now been postponed until April 28, 2022, which is the new “PDUFA date” or the date by which the FDA must respond to the new drug application.
The FDA has not asked Bristol Myers Squibb (BMS) to submit any additional data, but it wants to spend more time reviewing the proposed Risk Evaluation Mitigation Strategy or REMS which is the safety profile of the drug. The FDA can require REMS for certain drugs with safety concerns to ensure that the benefits of the medication will outweigh any risks.
BMS acquired the drug mavacamten, a first in class myosin inhibitor, through its $13.1 billion acquisition of San Francisco biotech company MyoKardia late last year.
You can read more about mavacamten and its journey in these past entries from HCMBeat:
I was recently asked by the good people at MyoKardia, now a subsidiary of Bristol Myers Squibb, if I would author a plain language summary of an article to be published in the journal Future Cardiology. This article summarizes the results of the EXPLORER-HCM trial, which showed that mavacamten, a new type of drug known as a “myosin modulator,” was successful in reducing HCM symptoms in subset of patients who took the drug during the clinical trial.
I was so fortunate to have Dr. Anjali Owens of the University of Pennsylvania Center for Inherited Cardiac Disease join me as co-author on the article. I also want to thank the teams at Bristol Myers Squibb and Cello Health Communications/SciFluent who supported us on this project. And, I so grateful to the former MyoKardia team and the other members of the EXPLORER-HCM Steering Committee who gave me the opportunity to witness a groundbreaking clinical trial from the front row.
This is the article. When you access the page, click to view the very informative short video, located in the upper right corner of the page, which explains how the drug works in very brief and concise terms.
Check it out!
Cynthia Burstein Waldman, Founder and Editor, HCMBeat
More positive data about the Bristol Myers Squibb experimental drug mavacamten was revealed at last weekend’s American College of Cardiology meeting and simultaneously published in The Lancet.
The data showed improvement in how patients felt taking the drug, as reported and quantified by the patients themselves. The clinical trial participants filled out a questionnaire called the KCCQ, or Kansas City Cardiomyopathy Questionnaire, 6 different times over the 38 weeks that the trial was ongoing.
The United States Food and Drug Administration (FDA) is expected to complete its review of mavacamten and release its decision on whether to approve the drug for sale in the U.S. by January 28, 2022.
This week, Bristol Myers Squibb submitted its New Drug Application for mavacamten to the FDA. Mavacamten is the first drug specifically designed to treat obstructive hypertrophic cardiomyopathy. The application was based on the recent positive results of the Phase 3 EXPLORER-HCM trial.
In October of last year, Bristol Myers Squibb paid $13.1 billion to purchase MyoKardia, the San Francisco based biotech company which developed mavacamten as a novel cardiac myosin modulator for the treatment of of HCM.
The FDA has assigned a Prescription Drug User Fee Act goal date of January 28, 2022 to the drug, which means that the FDA is expected to complete its review of mavacamten by January 28, 2022.
DISCLOSURES: CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVED AS A PATIENT ADVISOR ON THE STEERING COMMITTEE OF MYOKARDIA’S EXPLORER TRIAL AND IS AN AUTHOR OF THE STUDY AS PUBLISHED IN THE LANCET. CYNTHIA ALSO SERVES ON MYOKARDIA’S PATIENT ADVISORY BOARD.
The results from the Myokardia EXPLORER- MRI sub-study are in, and there is more positive news for mavacamten (formerly known as MYK-461). According to the results of this small 35 patient study, patients who took mavacamten showed reduction of left ventricular size and wall thickness on MRI. These patients also had a reduction in their left atrial volume. All three of these measurements are predictors of poor outcome for HCM patients Additionally, this study found a reduction in certain biomarkers such as NT-proBNP, which indicate heart stress and injury.
For more on the progress of mavacamten, read these previous entries on HCMBeat:
DISCLOSURES: CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVED AS A PATIENT ADVISOR ON THE STEERING COMMITTEE OF MYOKARDIA’S EXPLORER TRIAL. CYNTHIA ALSO SERVES ON MYOKARDIA’S PATIENT ADVISORY BOARD
This morning MyoKardia announced that it was being acquired by drug company Bristol Myers Squibb (BMS) for $13.1 billion. BMS plans to continue MyoKardia’s development of mavacamten as the first drug specifically intended to treat hypertrophic cardiomyopathy. The deal is expected to close before the end of 2020.
Last month, MyoKardia published positive results from its Stage 3 EXPLORER trial for obstructive HCM. Earlier this year, the FDA granted mavacamten breakthrough therapy designation which could shorten the FDA approval process by about 4 months. If all goes well, the drug could be available to HCM patients by the end of 2021.
The merger strengthens BMS’ cardiac offerings. Mavacamten will join Eliquis, a blood thinner that will go generic in 2026.
This is not MyoKardia’s first tie to Big Pharma. The French pharmaceutical company Sanofi invested $230 million into MyoKardia in 2014 but after their agreement expired in 2018, MyoKardia bought back the U.S. rights to its drugs for $80 million.
DISCLOSURES: HCMBEAT HAS RECEIVED UNRESTRICTED EDUCATIONAL GRANTS FROM MYOKARDIA. ADDITIONALLY, CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVED AS A PATIENT ADVISOR ON THE STEERING COMMITTEE OF MYOKARDIA’S EXPLORER TRIAL AND IS CREDITED AS AN AUTHOR OF THE STUDY AS PUBLISHED IN THE LANCET. CYNTHIA ALSO SERVES ON MYOKARDIA’S PATIENT ADVISORY BOARD.
The results of MyoKardia’s Stage 3 EXPLORER study for its experimental drug mavacamten were presented on Saturday at the European Society of Cardiology’s virtual annual meeting and contemporaneously published in The Lancet.
The findings from the study showed that mavacamten improved exercise capacity, reduced left ventricular outflow tract gradient (responsible for the obstruction in HCM) and improved New York Heart Association functional class, correlating with a reduction in symptoms and an improvement in quality of life in patients with obstructive hypertrophic cardiomyopathy.
This was the largest placebo controlled randomized trial ever conducted in HCM. Additionally, mavacamten is the first drug specifically developed for the treatment of hypertrophic cardiomyopathy. All drugs previously used for HCM symptoms were developed to treat other conditions and were used “off label” to treat HCM.
According to Florence, Italy’s Dr. Iacopo Olivotto, who presented the results to ESC’s virtual audience, mavacamten was generally well tolerated and did not appear to have serious side effects.
MyoKardia said the Explorer-HCM data will form the basis of its submission to the FDA which is planned for the first quarter of 2021. Last month, the company announced that the drug was awarded “Breakthrough Drug” designation by the FDA which it hopes will streamline the approval process.
Also, a new trial comparing mavacamten to septal myectomy and septal alcohol ablation entitled VALOR-HCM for patients with symptomatic, obstructive HCM and who are New York Heart Association Class III – IV who meet the criteria for septal reduction therapy and have been referred for such a procedure has just gotten underway with the first patient enrolled earlier this month.