Mavacamten: A Plain Language Summary of EXPLORER – HCM

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 on Mavacamten Presented at ACC Meeting

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.

Analysis of these responses showed that just over a third of patients who took mavacamten reported a substantial improvement in symptoms, though not all participants responded to the drug.  And, it is important to note that the improvements seen by patients returned to baseline once mavacamten was discontinued.

Mavacamten, formerly known as MYK-461, was developed by the San Francisco based company MyoKardia and acquired by Bristol Myers Squibb late last year for $13.1 billion.

You can read more about these results in

American Journal of Managed Care 

Fierce Biotech

Med Page Today

Healio.com

and here is an interview with Dr. Jay Edelberg of Bristol Myers Squibb about mavacamten.

Read more about history of mavacamten and other investigational drugs for HCM by searching the HCMBeat archives on the home page.

DISCLOSURES:  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 EXPLORER STUDY.  until recently CYNTHIA also SERVED ON MYOKARDIA’S PATIENT ADVISORY BOARD.

Click to access PIIS0140-6736(21)00763-7.pdf

Click to access PIIS0140-6736(21)00763-7.pdf

Click to access PIIS0140-6736(21)00763-7.pdf

Click to access PIIS0140-6736(21)00763-7.pdf

Click to access PIIS0140-6736(21)00763-7.pdf

Click to access PIIS0140-6736(21)00763-7.pdf

Experts Put Mavacamten in Perspective

An article published today in Circulation by HCM experts Dr. Steve Ommen of Mayo Clinic and Dr. Martin Maron of Tufts Medical Center, discusses the prospective use of mavacamten as a treatment for obstructive hypertrophic cardiomyopathy. The doctors conclude that while mavacamten (assuming that it is FDA approved in early 2022) will have its place in the HCM tool kit, it should not replace septal reduction therapy for severe HOCM.

In particular, the article points out that the EXPLORER-HCM study showed modest improvements in symptoms and functional capacity (peak V02), comparable to those seen in the RESET-HCM study, which highlighted the ability of regular exercise to improve functional status in HCM.  

The article notes that there has not yet been a study directly comparing mavacamten with septal reduction therapies such as septal myectomy and alcohol septal reduction. The VALOR-HCM study, which is currently recruiting, will look at these therapies compared head-to-head.  It is noteworthy that the majority of patients in the EXPLORER trial had Class II heart failure and were not the more severely compromised Class III and IV patients most likely to benefit from myectomy or alcohol septal ablation.

This article compared historical myectomy data against the findings from EXPLORER, concluding that septal myectomy produces a better result for patients, with gradients abolished in more than 95% of patients compared to only 50% of patients with mavacamten.  And, the article points out that 25% of the patients in the EXPLORER trial continued to have left ventricular outflow tract gradients greater than or equal to 50mmHg, which still qualified them for septal reduction therapy.

Maron and Ommen’s take-home message is that mavacamten will be a welcome addition to the arsenal of HCM drugs and is potentially suitable for patients who do not have severe symptoms, who do not have access to septal reduction at a HCM specialty center, or who wish to avoid more invasive therapies.  It also may be used in the same way as disopyramide, to defer surgery by improving symptoms to a tolerable level.

Lastly, this article points out that there is a need for longer term follow up to study the effects of cardiac remodeling caused by mavacamten.

While it is wonderful to have options, it is important that patients and their medical team consider all available information, including potential benefit and risk, before moving forward with medical therapy. 

Mavacamten Approaches Finish Line

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.

 

2 Companies Testing Drugs for HCM

Two San Francisco based companies are now conducting clinical trials for three drugs specifically targeting HCM.

Continue reading “2 Companies Testing Drugs for HCM”

MyoKardia Drug Moves to Next Phase

According to this press release, MyoKardia expects to dose the first patient in the EXPLORER-HCM trial of mavacamten (formerly known as MYK-461) for obstructive HCM in the second quarter of 2018.

MyoKardia says that it expects 220 patients to enroll in the 30 week long trial.  These patients will be randomly assigned to receive either mavacamten or a placebo.  Participants will also be able to continue on their normal beta blockers or calcium channel blockers.

 

Encouraging Results for MyoKardia HCM Drug

MyoKardia’s stock prices jumped today after their recent Stage II trial of the experimental drug mavacamten (formally known as MYK-461)  demonstrated a statistically significant reduction to left ventricular outflow tract gradients as well as improvement to aerobic capacity in patients with obstructive hypertrophic cardiomyopathy.  

Of the 10 patients who completed the study, 8 saw their gradient reduced to normal levels after 12 weeks on the drug.  The study also showed improvements in both peak oxygen consumption (peak VO2) and New York Heart Association classifications:  7 patients moved up one NYHA class while 2 patients improved by two classes.

The drug seemed to have mild to moderate side effects, though one patient was forced to drop out of the trial due to a recurrence of atrial fibrillation which necessitated discontinuation of mavacamten and a return to anti-arrythmic drugs which had been discontinued due to participation in the trial.

MyoKardia hopes to enroll between 200 and 250 patients in its next phase trial (Explorer HCM) which it plans to begin before the end of 2017.

MyoKardia also plans a clinical trial of mavacamten in non-obstructive HCM patients in the second half of 2017.

For more information on MyoKardia and  recent drugs being developed for HCM read these past blog entries:

MyoKardia HCM Drug Has Success in Cats

End of the Road for Eleclazine and Liberty HCM Study

HCM Drug Trial Advances to Next Round

Drug for Non-Obstructive HCM Moves Along