Tenaya Therapeutics Gets Go-Ahead for HCM Gene Therapy Trial

Tenaya Therapeutics announced on Monday that they have received FDA clearance to begin a Phase 1 clinical trial of targeted gene therapy for HCM.

Tenaya is developing TN-201, a first in class adeno-associated virus based therapy being developed to treat HCM caused by mutation(s) in the MYBPC3 gene. They anticipate that the trial will begin in the third quarter of 2023. The therapy delivers one fully functional MYBPC3 gene to the patient via injection with a deactivated virus. Tenaya hopes that this therapy will restore normal levels of the MYBPC3 protein, thereby halting disease progression, and even potentially reversing the course of the disease, after just a single treatment.

The TN-201 Phase 1b clinical trial will be a multi-center, open-label study designed to assess the safety of an intravenous infusion of TN-201. They hope to enroll at least 6 symptomatic, non-obstructive HCM patients who carry the MYBPC3 gene and who already have received an automatic implantable cardioverter defibrillator (ICD) as part of their treatment plan to date.

You can read the full  press release here.

Stay tuned to HCMBeat for updates!

Damar Hamlin’s Cardiac Arrest Should Move America to Action

Sudden cardiac arrest (SCA) has had a moment in the public eye this week.  The NFL game between the Cincinnati Bengals and Buffalo Bills, which was postponed after Bills safety Damar Hamlin suffered a cardiac arrest and collapsed on the field, was, according to CNN, the most-watched “Monday Night Football” telecast in ESPN history, averaging 23.8 million viewers.  

Damar Hamlin’s misfortune shined a public light on the grim reality that we as HCM patients live with every day:  the possibility we could suffer SCA at any moment without warning.

HCMBeat has written before about fellow HCM patient Lindsay Davis, who uses her platform as a former Miss Ohio to effect positive change for those with heart issues.

Lindsay pic 2022

In fact, Lindsay successfully lobbied for what is now known as “Lindsay’s Law,” which educates coaches, parents and athletes on the signs and symptoms of an underlying heart condition and removes a child with symptoms of heart disease from play until cleared by a cardiologist.

Now Lindsay has taken the opportunity to write a compelling op-ed for Newsweek about the need for cardiopulmonary resuscitation (CPR) and automatic external defibrillator (AED) training in the community. As Lindsay correctly points out, Damar Hamlin suffered a cardiac arrest in a NFL stadium surrounded by trainers, medical personnel and the most up to date equipment.  Children who play sports do not have the same  advantages. If a similar situation occurred on a school baseball diamond or a playground basketball court, it is likely that the bystanders would not be so prepared to render aid.

Some of you may know that I have been a lifelong fan of the New Orleans Saints football team. Gayle Benson, the owner of the Saints and the Pelicans, the local NBA team, did something that I hope will serve to inspire other professional teams to do for their communities. Mrs. Benson reached out and, finding there was a need, donated a total of 67 AEDs to the New Orleans Recreation Department (NORD) and the neighboring Jefferson Parish Recreation Department (JPRD).  Mrs. Benson will also provide CPR and AED training to NORD and JPRD personnel so they know what to do in the event of a cardiac arrest at their facilities.

Time is key when a person suffers a cardiac arrest.  According to the American Heart Association (AHA), 350,000 cases of cardiac arrest occur each year outside of a hospital, and the survival rate is less than 12 percent. CPR can double or triple the chances of survival.

A 2018 study highlighted on the AHA website shows the great benefit of being resuscitated by an AED following a cardiac arrest.  Read the following statistics:

  • Cardiac arrest victims who received a shock from a publicly-available AED had far greater chances of survival and being discharged from the hospital than those who did not; 66.5 percent versus 43 percent.
  • Cardiac arrest victims who received a shock from a bystander using a publicly-available AED had 2.62 times higher odds of survival to hospital discharge and 2.73 times better outcomes compared to victims who received their first  AED shock from emergency responders.
  • Victims who received an AED shock from a bystander (57.1 percent) using a publicly-available device instead of having to wait for emergency responders (32.7 percent) had near normal function and better outcomes.
  • Without a bystander using AED shock therapy, 70 percent of cardiac arrest patients either died or survived with impaired brain function (emphasis added).

More information about the chain of survival can be found on the American Heart Association website.

If you are looking for a New Year’s Resolution (or even if you aren’t!) take the time to learn CPR and learn how to use an AED today.  AEDs are so simple to use that even a 5th grader can administer properly.

And here is short video from Mayo Clinic showing how to do hands-only CPR.

And if you are a heart patient, think about getting an AED for your home.  I myself have one in my dining room.

AED dining room

Finally, I am sending out my best personal wishes to Damar Hamlin for a complete recovery. (As of this writing, he appears to be well on his way.)  

Most of all, I am sending out my sincere hope that this disturbing incident will improve the chances that the next person who suffers cardiac arrest will be lucky enough to be in the right place at the right time for complete resuscitation.

Wishing the entire HCM community a happy, and most of all a healthy, New Year. 

Cynthia Burstein Waldman  © 2023

All views expressed herein are my own.

Results Published from REDWOOD-HCM Phase 2 Trial

Results from Cytokinetics’ REDWOOD-HCM Phase 2 clinical trial of the experimental drug aficamten were just published in the Journal of the American College of Cardiology

Aficamten, a second generation myosin inhibitor, was administered to a small group of 28 patients as part of a phase 2 trial to determine safety of the drug of the drug in obstructive HCM over a 10 week period. 

No safety issues were found, while most trial participants experienced substantial reductions in left ventricular outflow tract gradients. Study participants also reported improvement to their symptoms, while blood tests showed improvement to certain biomarkers of heart stress.   

You can read more about the drug aficamten and Cytokinetics, the company behind it, in the below posts on HCMBeat. Next for aficamten is the Phase 3 trial entitled SEQUOIA-HCM.

Promising Data about Aficamten Presented at Meetings

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

LGE Seen on MRI Top Risk Factor for HCM

To date, risk assessment in patients with hypertrophic cardiomyopathy (HCM) has largely focused on whether there is a need for an implantable defibrillator by evaluating an individual patient’s short term risk of sudden death, but has not looked at the long term risks of heart failure and other adverse outcomes over time.

A recent retrospective study by European HCM specialists asked the question of whether the addition of advanced imaging could assist in pinpointing patients at high risk of heart failure and/or other serious HCM complications over time. 

Continue reading “LGE Seen on MRI Top Risk Factor for HCM”

HCM Genes Common in General Population

A recent study sought to find how common genetic cardiomyopathies are in the general population. 

By studying United Kingdom Biobank samples from 200,643 people who had undergone complete genetic sequencing, researchers established that genes linked to HCM are found in one out of every 149 people! 

More than half of those identified as having a HCM gene had a mutation in the MYBPC3 gene, making it the most common HCM gene in this sampling.

Jardiance for HCM Patients?

A recent study published in the American Journal of Cardiology found that patients with non-obstructive hypertrophic cardiomyopathy and diabetes showed significant improvements to diastolic heart function and BNP (a hormone produced by the body which indicates heart wall stress) from the use of a drug used for diabetes known as a sodium glucose co-transponder 2 inhibitor (SGLT2).  

This class of drugs is commonly used to lower blood sugar in diabetics.  One SGLT2 in common usage is Jardiance (empagliflozin).

Since treatments for non-obstructive HCM patients are so limited, this class of drugs presents a potential treatment opportunity for non-diabetic HCM patients as well. 

Hey all you researchers out there – sounds like a good clinical trial!

HCM Impact on Mental Health

A recent study by Korean researchers found that HCM is associated with mental health disorders, especially during the first year after a HCM diagnosis.  

This study only scratches the surface of the topic, but it does bring up an important point which we hope that medical providers will take to heart:  the mental health of HCM patients is just as important as their physical health and sometimes, mental health referrals and/or medications may be a necessary part of the HCM treatment plan.

Mavacamten Approved in Canada

Bristol Myers Squibb’s first in class drug  mavacamten (brand name Camzyos) has been approved by Health Canada for the treatment of obstructive hypertrophic cardiomyopathy.

Longer Term Results for Mavacamten

The VALOR-HCM trial  was a Phase 3 clinical trial which compared the Bristol Myers Squibb drug mavacamten (brand name Camzyos) to septal reduction therapy (myectomy and septal alcohol ablation) over a 16 week period.  At the end of the 16 week period, the patients originally randomized to the placebo were prescribed mavacamten, while those originally prescribed mavacamten continued taking the drug for an additional 16 weeks for a total of 32 weeks

At last weekend’s American Heart Association meeting in Chicago and simultaneously published in Circulation, lead investigator Dr. Milind Desai of the Cleveland Clinic announced that after 32 weeks of mavacamten treatment, patients continued to see positive cardiac remodeling, as well as improvement to left ventricular outflow tract gradient, diastolic function and quality of life. This ultimately allowed a whopping 88% of patients enrolled in the trial to avoid a septal reduction procedure. 

Similar results were noted in those patients who began mavacamten after an initial 16 weeks on a placebo.

This is good news for HCM patients!

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.

Continue reading “The Future of HCM Treatment”