Aficamten Updates from Cytokinetics

At two recent meetings, South San Francisco biotech company Cytokinetics presented encouraging data on its experimental drug for hypertrophic cardiomyopathy, aficamten (formerly known as CYK-274). 

Results from the REDWOOD-HCM open label extension study were presented as a Late Breaking Presentation at the European Society of Cardiology Heart Failure Congress. These results showed that after 6 months of treatment with aficamten, patients improved by one or more New York Heart Association class, with a corresponding improvement in symptoms. Additionally, there were significant reductions seen in left ventricular outflow tract gradients.  According to the presentation, the drug is safe and well tolerated, and only a small decreases in left ventricular ejection fraction was seen in a small number of trial participants. Improvements were also seen in cardiac biomarkers NTpro-BNP and troponin, which are measured via blood test.

Also, data was presented at the American Society of Echocardiography 33rd Annual Scientific Sessions which showed that after 10 weeks of treatment with aficamten, a significant reduction in left atrial volume index was noted, as well as a what appeared to be a lessening of left ventricular hypertrophy.  Improvements in ventricular relaxation and filling, as well as in mitral valve dynamics were also observed.

If you would like to learn more about aficamten, here are some past entries on HCMBeat:

2 Companies Testing Drugs for HCM

HCM Clinical Trials – the Latest News

The Future of HCM Care

Positive Signs from REDWOOD-HCM

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

Aficamten Gets “Breakthrough Drug” Status from FDA

More on Aficamten & Mavacamten from ACC 2022

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

Cytokinetics Moves Forward with HCM Drug Trial

Cytokinetics Announces Positive Results from REDWOOD-HCM Phase 2 Clinical Trial

Increased COVID Risk for HCM Patients

A recent retrospective study of HCM patients with COVID-19 concluded that HCM patients are at increased risk of hospitalization and death from a COVID-19 infection. 

In particular, the study found that the following groups of HCM patients were at increased risk of adverse complications from COVID-19:

  • patients with the obstructive form of HCM
  • patients with left ventricular systolic dysfunction
  • older patients
  • patients who also have other high risk conditions for COVID-19 such as hypertension, diabetes, obesity or those who are smokers 

Based on this data, the researchers suggest “the need for aggressive and systematic implementation of prophylactic measures for SARS-COV-2 in patients with inherited cardiac disease.”   

At this time, such measures include vaccinations, masking, and therapeutic agents such as Paxlovid and monoclonal antibodies.

IMPORTANT NOTE:  This study finished enrollment just as COVID-19 vaccines became available. Hence, these results do not take into account the effect of vaccinations or newer COVID-19 therapeutics such as Paxlovid.  

More on Aficamten & Mavacamten from ACC 2022

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.

Continue reading “More on Aficamten & Mavacamten from ACC 2022”

VALOR-HCM Trial – Mavacamten vs. Septal Reduction Therapy – RESULTS ARE IN!

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.

Continue reading “VALOR-HCM Trial – Mavacamten vs. Septal Reduction Therapy – RESULTS ARE IN!”

Traditional Cardiovascular Risk Factors Worsen HCM

According to this recent article in the European Heart Journal, traditional cardiovascular risk factors such as obesity, hypertension and diabetes are associated with more severe forms of HCM. Therefore, the authors suggest that these additional risk factors should be aggressively managed so as to limit their impact on HCM.  

Gene Therapy for HCM

A recent article on Biospace.com describes a method of targeted gene therapy for HCM patients currently being developed by Tenaya Therapeutics. This therapy is intended for patients whose HCM is caused by a mutation in the MYBPC3 gene.

According to Tenaya CEO Faraz Ali, animal models show that this therapy can reverse declining heart function.

You can find more information on about Tenaya’s approach here.

Arrhythmia Monitoring in HCM

Arrhythmia monitoring in HCM patients is used not only for determining risk of sudden death and potential need for an implantable defibrillator, but also for detecting atrial fibrillation (AFib) and implementing anti-coagulation for stroke prevention.

A recent paper provides an overview of the usefulness of arrhythmia monitoring in patients with HCM. 

Continue reading “Arrhythmia Monitoring in HCM”

Worse Exercise Capacity in Women with HCM

According to this recent study looking at exercise capacity in patients with HCM, women with HCM demonstrated reduced exercise capacity when compared to men.  This paper theorizes that the differences are likely attributable to passive diastolic properties and that these could aid in the development of interventions specifically targeted for women.

Aficamten Gets “Breakthrough Drug” Status from FDA

Cytokinetics has announced that its experimental drug aficamten, currently in trials as a potential treatment for obstructive hypertrophic cardiomyopathy, has received breakthrough therapy designation from the FDA.  This designation is awarded by the FDA to certain drugs which may offer substantial improvement to patients over available therapies. The designation could shorten the FDA approval process for the drug by about 4 months.

You can read more about Cytokinetics and aficamten in these older posts from HCMBeat: 

Interview with Dr. Martin Maron about Cytokinetic’s Drug Aficamten 

Cytokinetics Announces Positive Results from REDWOOD-HCM Phase 2 Clinical Trial

Cytokinetics Moves Forward with HCM Drug Trial

Cytokinetics Announces its Phase 2 Clinical Trial

Positive Signs from REDWOOD-HCM

The Future of HCM Care

HCM Clinical Trials – the Latest News

2 Companies Testing Drugs for HCM

Scientists Get $10 Million Grant to Develop HCM Treatments

 

 

FDA Approval of Mavacamten Delayed

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:

2 Companies Testing Drugs for HCM

HCM Clinical Trials – the Latest News

HCM Drug Shows Improvement to Heart Structure

More Positive Data on Mavacamten Presented at ACC Meeting

More Positive Results for MyoKardia Drug

MyoKardia Announces Positive Results from EXPLORER Trial

MyoKardia’s EXPLORER Trial Big Success

Mavacamten Approaches Finish Line