Targeted Gene Therapy for HCM

The expanding field of personalized medicine has not left hypertrophic cardiomyopathy behind. In fact, two companies are currently developing targeted gene therapies for HCM patients. Each therapy targets a separate and distinct HCM gene mutation.

Tenaya Therapeutics, located in the San Francisco area, is developing a therapy called TN-201 which is directed at mutations in the Myosin Binding Protein C3 (MYBPC3) gene. The therapy has shown favorable results in mice.  In May of this year, Tenaya received Orphan Drug Designation from the U.S Food and Drug Administration. An Orphan Drug Designation confers certain tax and economic incentives on companies developing a treatment for rare conditions.

Meanwhile, this week, Lexeo Therapeutics acquired Stelios Therapeutics, a San Diego based company developing a therapy for HCM patients with a mutation in the TNNI3 gene. These TNNI3 patients comprise somewhere between 5% and 7% of all patients with HCM, or approximately 30,000 people.  The underpinnings of this research come from the University of California, San Diego.

HCMBeat will continue following these developments. It is a busy and exciting time in the treatment of HCM!

Drug Trial for Non-Obstructive HCM

Yet another company is developing a new drug for hypertrophic cardiomyopathy, and this time, the drug is intended for non-obstructive HCM patients.  The company is Imbria Pharmaceuticals, and this week they announced the randomizing of the first patient in their Phase 2 study of the drug IMB-101 in patients with non-obstructive HCM.  The study, called IMPROVE-HCM, is a Phase 2 study that will look at the safety and tolerability of this drug in non-obstructed HCM patients. IMB-101 is designed to increase the efficiency of the heart’s use of energy which will be measured through cardiopulmonary exercise testing over a 12 week period.

You can read this press release and you can read more about the trial on ClinicalTrials.gov here.

Can This Formula Predict AFib in HCM Patients?

HCM specialists at Tufts Medical Center and Toronto General Hospital have devised a formula which they hope will help predict which HCM patients may go on to develop atrial fibrillation (“AFib”) over time. This tool can assist doctors in determining which patients are at highest risk so that these patients can be closely monitored and treated appropriately. AFib can be extremely dangerous for HCM patients since it can precipitate a stroke if not appropriately treated.   

Because existing tools to predict atrial fibrillation have not proven to be accurate for HCM patients, the researchers studied 1900 HCM patients with the goal of devising a new tool to help HCM patients and their physicians learn their personal risk for AFib over a 2 and 5 year period.

CALCULATE YOUR RISK SCORE:

The formula works as follows:  Find your left atrial diameter on your most recent echocardiogram report.  On the chart below, find the number of points (listed in the 2nd column) that corresponds with your left atrial measurement (measured in millimeters). Then, find the number in the 2nd column that corresponds to your current age range.  Add these two numbers together. From that sum, subtract the number listed in the 2nd column that correlates with your age range when you were first diagnosed with HCM.  Lastly, if you have heart failure symptoms, add in 3 points.  The total is your score.

You can calculate using the table below, or you can use this online calculator which gives you your 2 and 5 year risk.

1624763659016blob

WHAT DOES YOUR RISK SCORE MEAN:

Low Risk scores are between 8 – 17

Intermediate Risk scores are between 18 – 21

High Risk scores are between 22 – 31

As always, discuss with your doctor. Everyone has individual factors which will influence their degree of risk. This tool is intended as a general guideline to facilitate discussion with your physician.

Positive Myectomy Outcomes for Patients 65+

According to a recent retrospective study at Oregon Health & Sciences University, appropriately selected patients 65 or older who underwent septal myectomy for obstructive hypertrophic cardiomyopathy (HOCM) have surgical outcomes similar to younger patients. Therefore, older age should NOT be an automatic disqualifier for myectomy. All potential treatments for outflow tract obstruction should be considered, with age being only one of many factors influencing the decision.  

More Positive Data on Mavacamten Presented at ACC Meeting

More positive data about the Bristol Myers Squibb experimental drug mavacamten was revealed at last weekend’s American College of Cardiology meeting and simultaneously published in The Lancet.

The data showed improvement in how patients felt taking the drug, as reported and quantified by the patients themselves. The clinical trial participants filled out a questionnaire called the KCCQ, or Kansas City Cardiomyopathy Questionnaire, 6 different times over the 38 weeks that the trial was ongoing.

Analysis of these responses showed that just over a third of patients who took mavacamten reported a substantial improvement in symptoms, though not all participants responded to the drug.  And, it is important to note that the improvements seen by patients returned to baseline once mavacamten was discontinued.

Mavacamten, formerly known as MYK-461, was developed by the San Francisco based company MyoKardia and acquired by Bristol Myers Squibb late last year for $13.1 billion.

You can read more about these results in

American Journal of Managed Care 

Fierce Biotech

Med Page Today

Healio.com

and here is an interview with Dr. Jay Edelberg of Bristol Myers Squibb about mavacamten.

Read more about history of mavacamten and other investigational drugs for HCM by searching the HCMBeat archives on the home page.

DISCLOSURES:  CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVED AS A PATIENT ADVISOR ON THE STEERING COMMITTEE OF MYOKARDIA’S EXPLORER TRIAL AND IS CREDITED AS AN AUTHOR OF THE EXPLORER STUDY.  until recently CYNTHIA also SERVED ON MYOKARDIA’S PATIENT ADVISORY BOARD.

Click to access PIIS0140-6736(21)00763-7.pdf

Click to access PIIS0140-6736(21)00763-7.pdf

Click to access PIIS0140-6736(21)00763-7.pdf

Click to access PIIS0140-6736(21)00763-7.pdf

Click to access PIIS0140-6736(21)00763-7.pdf

Click to access PIIS0140-6736(21)00763-7.pdf

100,000 Views!!!!

Today, HCMBeat.com surpassed 100,000 views!

 

Big thanks to everyone who has supported HCMBeat over the last 5 years, especially all of the doctors and researchers who spend their days working to improve the lives of patients with HCM.

 

I hope that this blog will continue to inform the HCM community about the latest news and information related to hypertrophic cardiomyopathy . 

 

The last few years have been exciting for HCM patients and the future looks even brighter!

 

Happy Mother’s Day to all.

 

Cynthia

 

Cynthia Burstein Waldman, HCM Patient, Founder and Editor, HCMBeat.com

Chinese Study Links Depression to Worse HCM Outcomes

A recent Chinese study found that patients with hypertrophic cardiomyopathy who also suffered from clinical depression had a higher risk of sudden cardiac death and/or heart failure. 

The researchers behind this study hypothesize that psychological treatment for depression could improve clinical outcomes in these patients and they suggest that further research is warranted.

Kids with HCM

A recent study published in the European Heart Journal using data collected from the SHaRe Registry found that while childhood onset HCM (15% of all HCM) is far less common than adult onset HCM, it is often more serious.

Children with HCM are more likely to have sarcomere mutations, have a higher risk of ventricular arrhythmias, and are twice as likely as adults to require advanced interventions like ventricular assist devices, heart transplant or other advanced heart failure therapies. 

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.