Cytokinetic’s Drug Aficamten & Upcoming HCM Summit – Interview with Dr. Martin Maron

Editor’s note:  You have probably noticed a distinct uptick in clinical trials of potential treatments for hypertrophic cardiomyopathy.  HCMBeat has been following this trend and has previously published a host of stories about such trials, including this story about the positive results from the REDWOOD-HCM Phase 2 clinical trial, as well as past stories discussing the biopharmaceutical company Cytokinetics, its  drug aficamten (previously known as CK-274), and the REDWOOD-HCM trial.

Some of these earlier stories are as follows: 

2 Companies Testing Drugs for HCM

HCM Clinical Trials – the Latest News

Positive Signs from REDWOOD-HCM

Cytokinetics Moves Forward with HCM Drug Trial

Recently, Cynthia Waldman of HCMBeat had the opportunity to speak over Zoom with Dr. Martin Maron, who recently served as the principal investigator of Cytokinetics’ REDWOOD trial.  The conversation focused both on Cytokinetic’s drug aficamten (previously known as CK-274), and the new class of drugs known as “myosin inhibitors.”  What follows is a transcript of their conversation (which has been edited for readability). 

Continue reading “Cytokinetic’s Drug Aficamten & Upcoming HCM Summit – Interview with Dr. Martin Maron”

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.

 

Could Septal Reduction Outcomes Vary by Gender?

A retrospective analysis recently published in JACC: Cardiovascular Interventions suggests that that the risks of septal reduction therapy may differ for men and women.

In particular, the study found that the need for a pacemaker following septal alcohol ablation was almost 3 times more likely for a female than for a male.

The authors suggested that the reason for this difference may have been more advanced disease among female patients, and a higher instance of myocardial fibrosis and calcification.  

Whatever the reason, this is another factor for patients to consider before deciding which method of septal reduction is best for them.

Myectomy Sooner?

An article by doctors at the Cleveland Clinic recently published in the Journal of the American Heart Association advocates for earlier surgical intervention for patients with obstructive hypertrophic cardiomyopathy (HCM).   

According to this article, obstructed HCM patients who undergo myectomy earlier have better long term survival. Therefore, these doctors take the position that patients should not wait until they become severely symptomatic and/or have run out of medical options to undergo myectomy surgery. 

Meanwhile, an accompanying editorial by Dr. Mark Sherrid of NYU Langone Health is to the contrary.  Dr. Sherrid argues that medications like disopyramide (Norpace) are effective in reducing symptoms and that the inherent risks from open heart surgery are not outweighed by a theoretical improvement in longevity.

Regardless of the timing of surgery, Dr. Sherrid points out that with multiple companies now developing novel treatments for HCM, visibility of the disease will increase which will ultimately result in better patient outcomes for all with HCM. 

 

 

 

Cytokinetics Announces its Phase 2 Clinical Trial – “Redwood-HCM”

Cytokinetics today announced that its Phase 2 double-blind study of its experimental drug CK-274 entitled “REDWOOD-HCM” (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM (hypertrophic cardiomyopathy) has begun enrollment.  The trial will enroll patients with symptomatic, obstructive HCM.

CK-274 is a next-generation cardiac myosin inhibitor which the company hopes will prove to be beneficial for the treatment of hypertrophic cardiomyopathy (HCM).

There are currently two companies in clinical trials for HCM:  Cytokinetics and MyoKardia. You can read more about their efforts here and here.

 

Can a Smartwatch Detect HOCM?

According to a limited study recently published in Nature, researchers were able to detect obstructive HCM (HOCM) using a noninvasive optical sensor contained in many commercial smartwatches.

How the Technology Works

These watches used photoplethysmography, a noninvasive optical method used to detect blood volume changes in the microvascular bed at the skin surface.  The same technology is used in clinical pulse oximeters and is now widely incorporated in commercial smartwatches that have heart rate detection.

Continue reading “Can a Smartwatch Detect HOCM?”

Positive Results for MyoKardia Drug Mavacamten

This week in the journal Annals of Internal Medicine, MyoKardia reported positive results from its open label phase 2 clinical trial of its drug mavacamten (formerly known as MYK-461) for obstructive hypertrophic cardiomyopathy. The study was conducted at 5 HCM centers and enrolled 21 subjects with  obstructive HCM. All subjects saw some degree of improvement to their condition after taking mavacamten.

Continue reading “Positive Results for MyoKardia Drug Mavacamten”

Exercise Testing Important for HCM Patients

According to a recent study by doctors at Tufts HCM Center in collaboration with colleagues in Italy, exercise testing is an invaluable tool in the assessment of hypertrophic cardiomyopathy patients.

In particular, two types of exercise testing are most valuable for HCM patients:

  • Exercise Echocardiogram:  These tests are valuable in determining whether a patient has obstruction.  It provides a physiological way to measure whether or not a patient has an obstructed left ventricular outflow tract and hence, may potentially be in need of an invasive procedure to treat the obstruction.  According to the article, approximately 1/3 of HCM patients have latent obstruction which may only be seen during or after exercise.  This obstruction is not always apparent from their resting echocardiogram.

and

  • Cardiopulmonary Exercise Testing:  These tests help determine functional capacity and provide a quantifiable indicator of heart failure symptoms.  This test  can identify patients in need of more aggressive treatment options, or who are potentially in need of transplant.  A particularly valuable piece of data from this test is the “VO2 max” score, which is a measure of the maximum rate of oxygen consumption during exercise which reflects the cardiorespiratory fitness level of a person.

*Editor’s note – Exercise testing was particularly informative and important in my own HCM treatment.  It was only after my doctors performed an exercise echo that the extent of my obstruction became apparent.  The symptoms I had been suffering appeared to be out of proportion to what was visualized on my resting echo.  The exercise echo helped my doctors understand the cause of my symptoms which made the next step, in my case a myectomy, much clearer.

You can read my full story here .

 

 

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