The Future of HCM Treatment

Doctors from the University of Pennsylvania this week published an overview of current therapies available for the treatment of HCM.  While this article mentions all of the old standards – beta blockers, calcium channel blockers, myectomy and alcohol ablation, the real focus is on the future of HCM treatment. In particular, the article describes several new and/or experimental therapies which look promising for the future. These include:

Myosin inhibitors:

like mavacamten and aficamten.  Two more myosin inhibitors with similar properties are currently under investigation.

Valsartan: 

The angiotensin II receptor blocker valsartan has shown promise in reducing left ventricular mass in early HCM

Septal Reduction:

Novel methods of septal reduction have been used experimentally with promising results.  These include:

    • Percutaneous septal radiofrequency ablation which uses the same radiofrequency ablation techniques previously used to treat arrhythmias to treat outflow tract obstruction.

    • Transcatheter myotomy which has shown promising early results in pigs and so far on one person. In this procedure, catheters and guidewires are inserted into the basal septum and electrosurgery is used to cut the heart muscle.

Gene Therapy:

Cardiac gene therapy utilizes adeno-associated viruses (AAV) to introduce the therapy.  This therapy is in early stages, but could be a future option for a subset of patients with genetic HCM.

More Research Needed for Patients with Non-Obstructive HCM:

A phase 2 trial called IMPROVE-HCM by a company called Imbria Pharmaceuticals is looking at the drug IMB-101 in patients with nonobstructive hypertrophic cardiomyopathy while Maverick-HCM showed that mavacamten was safe in non-obstructive HCM and improved cardiac biomarkers. However, mavacamten has not yet been tested in a Phase 3 trial for patients with non-obstructive HCM.  A cohort of the REDWOOD-HCM phase 2 trial for Cytokinetics’ drug aficamten in non-obstructive patients is currently in progress.

Non-obstructed patients need more options!

Promising Data about Aficamten Presented at Meetings

Encouraging data about the Cytokinetics investigational drug aficamten was presented over the weekend at 2 scientific meetings held in Washington D.C.

Continue reading “Promising Data about Aficamten Presented at Meetings”

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”

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

Cytokinetics today announced positive topline results for its experimental drug CK-274 from its recent Phase 2 REDWOOD-HCM trial for patients who have obstructive hypertrophic cardiomyopathy (HOCM).

According to the press release, this drug, a next-in-class cardiac myosin inhibitor, showed consistent and meaningful reduction in left ventricular outflow tract gradients in HOCM with its effects evident within 2 weeks of starting the drug. The benefits continued until the end of treatment 10 weeks later. No patients had to  discontinue the drug or take a break from treatment due to reduced left ventricular ejection fraction. And, the drug was well tolerated and appeared to be free from significant side effects.

Cytokinetics plans to commence a Stage 3 for CK-274 trial by the end of 2021. Full results of the Stage 2 REDWOOD study will be presented at an upcoming scientific meeting.

Cytokinetics Moves Forward with HCM Drug Trial

This week Cytokinetics announced that the first patient in Cohort 2 of their REDWOOD-HCM trial has been dosed.

Cytokinetics is testing the safety and tolerability of the cardiac myosin inhibitor CK-274 for the potential treatment of hypertrophic cardiomyopathy.  The trial already enrolled completed enrollment of 18 patients in the first cohort.  Sites are located across North America and Europe and results are expected in the middle of this year.

Separately, Cytokinetics announced that CK-274 has been granted an orphan drug designation by the FDA. This designation confers certain benefits and financial incentives for drugs intended to treat conditions affecting fewer than 200,000 people in the U.S.

Positive Signs from REDWOOD-HCM

Cytokinetics announced this week the progression of REDWOOD-HCM, its ongoing Phase 2 clinical trial of CK-274, a cardiac myosin inhibitor for the treatment of HCM.

According to the press release, preliminary results show substantial reductions in left ventricular outflow tract gradients (LVOT), with only modest decreases in left ventricular ejection fraction. (LVEF). 

Based on this early positive data, the study will continue and will enroll a second group of approximately 18 patients. 

Cytokinetics hopes to have results from REDWOOD-HCM in the middle of 2021, and hopes to begin a Phase 3 trial for CK-274 by the end of 2021.

For detailed information about this trial see ClinicalTrials.gov.

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.