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!

VANISH Trial: Valsartan Shows Positive Results for Early HCM

A common cardiac drug called valsartan has shown positive results in those who carry the gene for hypertrophic cardiomyopathy but who do not have overt disease. 

As reported by Dr. Carolyn Ho of Brigham and Women’s Hospital and Harvard Medical School at the online European Society of Cardiology meeting, the Phase 2 double blind VANISH trial looked at 178 pre-symptomatic young people who carried a sarcomere gene mutation known to cause HCM.  These patients were randomly assigned to take either  valsartan, an angiotensin II receptor blocker (ARB), or a placebo.  

At the time of trial enrollment, these patients showed no or only mild signs of the disease.  At the end of the two year trial, the individuals who took valsartan had a better overall cardiac picture compared to the group taking only the placebo.

Dr. Ho had this to say in a story about the trial results in Mirage News:  

“Valsartan improved cardiac structure/function and remodeling in patients with early stage sarcomeric HCM, suggesting that this strategy may help prevent disease progression among those who have received a genetic diagnosis of HCM.”  

“Our results suggest that valsartan may not only stabilize disease progression but may also promote improvement.” 

You can also read this summary of the presentation on MedPage Today.