HCM Clinical Trials – the Latest News

NEWS FROM MYOKARDIA

MyoKardia recently announced a new clinical trial of its drug, mavacamten (formerly known as MYK-461) which will compare the clinical results of mavacamten with septal reduction therapies currently used in clinical practice, i.e. the open heart surgical procedure known as septal myectomy and the catheter based procedure known as alcohol septal ablation.

The study will be run by the Cleveland Clinic with Dr. Milind Desai serving as principal investigator.  MyoKardia expect to begin enrolling patients in early 2020.

Read the press release here.

 

NEWS FROM CYTOKINETICS:

Cytokinetics released positive data from its Phase 1 study of the drug currently known as CK-274 in a poster session at the HFSA 23rd Annual Scientific Meeting in Philadelphia.  The study found that CK-274 was safe and well tolerated, while no serious adverse events or negative changes to vital signs, ECGs or laboratory tests were observed.

The company will now be moving into a Phase 2 clinical trial of CK-274 in patients with obstructive hypertrophic cardiomyopathy, expected to begin in late 2019.

Read their press release here.

 

 

DISCLOSURES:  HCMBEAT HAS RECEIVED PAST UNRESTRICTED EDUCATIONAL GRANTS FROM MYOKARDIA.  ADDITIONALLY, CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVES AS A PATIENT ADVISOR ON THE STEERING COMMITTEE FOR MYOKARDIA’S EXPLORER TRIAL.

2 Companies Testing Drugs for HCM

Two San Francisco based companies are now conducting clinical trials for three drugs specifically targeting HCM.

MyoKardia, which was founded in 2012 by a group of HCM researchers (including Stanford’s James Spudich, one of the founders of Cytokinetics – the second company conducting a HCM drug trial – see below), was the first entrant into the HCM area with the development of its drug, mavacamten (formerly known as MYK-461).

Mavacamten is currently the subject of the Phase 3 EXPLORER-HCM clinical trial for obstructive HCM, now fully enrolled with results expected in 2020, as well as the Phase 2 MAVERICK-HCM trial for non-obstructive HCM, with results are expected later this year.

And, MyoKardia announced this week that it is will begin testing a second drug for HCM.  The new drug, currently known as MYK-224, is the subject of a new Phase 1 clinical trial.  This drug targets the sarcomeric proteins of the heart muscle like MyoKardia’s first drug, mavacamten. According to the press release, MYK-224 may provide dosing advantages for some patients over other drugs.

Cytokinetics, a company founded in 1998 which was previously focused on other muscle related conditions like ALS, has decided to set its sights on HCM.  Cytokinetics is currently conducting a Phase 1 clinical trial assessing the safety and tolerability of its drug CK-274, a cardiac myosin inhibitor intended to reduce cardiac contractility.

At a recent cardiology meeting in Boston, Cytokinetics presented data showing that CK-274 decreased cardiac contractility in healthy animals.

Stay tuned to HCMBeat for the latest details and updates about these drugs.

UPDATE:  Data Presented at August 31, 2019 European Society of Cardiology Congress in Paris

At ESC, MyoKardia announced results from the PIONEER-Open Label Extension study from 12 patients who had been enrolled in the Phase 2 PIONEER-HCM study of mavacamten. These patients were evaluated after a total of 36 weeks on the drug.  The study results showed reduction in both resting and provoked left ventricular outflow tract gradients, while left ventricular ejection fraction remained normal at all times.  Further, certain biomarkers of heart disease showed improvement with mavacamten treatment.  Most strikingly, NT-proBNP, a blood indicator of cardiac wall stress, decreased almost to normal.   

DISCLOSURES:  HCMBEAT HAS RECEIVED PAST UNRESTRICTED EDUCATIONAL GRANTS FROM MYOKARDIA.  ADDITIONALLY, CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVES AS A PATIENT ADVISOR ON THE STEERING COMMITTEE FOR MYOKARDIA’S EXPLORER TRIAL.

Can a Smartwatch Detect HOCM?

According to a limited study recently published in Nature, researchers were able to detect obstructive HCM (HOCM) using a noninvasive optical sensor contained in many commercial smartwatches.

How the Technology Works

These watches used photoplethysmography, a noninvasive optical method used to detect blood volume changes in the microvascular bed at the skin surface.  The same technology is used in clinical pulse oximeters and is now widely incorporated in commercial smartwatches that have heart rate detection.

Continue reading “Can a Smartwatch Detect HOCM?”

Positive Results for MyoKardia Drug Mavacamten

This week in the journal Annals of Internal Medicine, MyoKardia reported positive results from its open label phase 2 clinical trial of its drug mavacamten (formerly known as MYK-461) for obstructive hypertrophic cardiomyopathy. The study was conducted at 5 HCM centers and enrolled 21 subjects with  obstructive HCM. All subjects saw some degree of improvement to their condition after taking mavacamten.

Continue reading “Positive Results for MyoKardia Drug Mavacamten”

MyoKardia Announces Positive Result for Mavacamten for Treatment of HOCM

This week, MyoKardia announced positive data on its experimental drug for HCM, mavacamten (formerly known as MYK-461), for obstructive HCM.

Continue reading “MyoKardia Announces Positive Result for Mavacamten for Treatment of HOCM”

MyoKardia Drug Moves to Next Phase

According to this press release, MyoKardia expects to dose the first patient in the EXPLORER-HCM trial of mavacamten (formerly known as MYK-461) for obstructive HCM in the second quarter of 2018.

MyoKardia says that it expects 220 patients to enroll in the 30 week long trial.  These patients will be randomly assigned to receive either mavacamten or a placebo.  Participants will also be able to continue on their normal beta blockers or calcium channel blockers.

 

HIGHLIGHTS FROM THE INTERNATIONAL HCM SUMMIT, PART IV

Editor’s Note:  This is the 4th of 4 blog entries which summarizes the presentations given at the recent International HCM Summit VI in Boston.  The presenter and their hospital affiliation are noted below, along with the topic of their presentation.  When possible, you may access the presenters’ slides via hyperlink by clicking on the name. (Note that not all presenters made their slides available).

To see Part I of this series of highlights from the HCM Summit VI, click here, to see Part II of this series click here, and to see part III of this series. click here.

Continue reading “HIGHLIGHTS FROM THE INTERNATIONAL HCM SUMMIT, PART IV”

Encouraging Results for MyoKardia HCM Drug

MyoKardia’s stock prices jumped today after their recent Stage II trial of the experimental drug mavacamten (formally known as MYK-461)  demonstrated a statistically significant reduction to left ventricular outflow tract gradients as well as improvement to aerobic capacity in patients with obstructive hypertrophic cardiomyopathy.  

Of the 10 patients who completed the study, 8 saw their gradient reduced to normal levels after 12 weeks on the drug.  The study also showed improvements in both peak oxygen consumption (peak VO2) and New York Heart Association classifications:  7 patients moved up one NYHA class while 2 patients improved by two classes.

The drug seemed to have mild to moderate side effects, though one patient was forced to drop out of the trial due to a recurrence of atrial fibrillation which necessitated discontinuation of mavacamten and a return to anti-arrythmic drugs which had been discontinued due to participation in the trial.

MyoKardia hopes to enroll between 200 and 250 patients in its next phase trial (Explorer HCM) which it plans to begin before the end of 2017.

MyoKardia also plans a clinical trial of mavacamten in non-obstructive HCM patients in the second half of 2017.

For more information on MyoKardia and  recent drugs being developed for HCM read these past blog entries:

MyoKardia HCM Drug Has Success in Cats

End of the Road for Eleclazine and Liberty HCM Study

HCM Drug Trial Advances to Next Round

Drug for Non-Obstructive HCM Moves Along

MyoKardia HCM Drug Has Success in Cats

MyoKardia’s experimental drug MYK-461, currently in Stage 2 trials for humans, has now been shown to eliminate left ventricular obstruction in five cats with HCM. It has already been shown to inhibit traits of HCM in mice.

Addressing these findings, Associate Professor Joshua Stern, chief of the Cardiology Service at the University of California, Davis, veterinary hospital, stated:

“There has been little to no progress in advancing the treatment of HCM in humans or animals for many years,” Stern said. “This study brings new hope for cats and people.

Based on these positive results, U.C.Davis is hoping to conduct a clinical trial of MYK-461 to determine whether it could become the standard of care for cats with HCM.

The full text of the article published in Plos One can be found here.

End of the Road for Eleclazine and Liberty HCM Study

 Eleclazine:  The Liberty HCM Trial

It appears to be the end of the road for the Gilead drug eleclazine, a late sodium channel inhibitor previously known as GS-6615.  Eleclazine, with properties similar to the anti-angina drug ranolazine (which was approved by the FDA in 2006), was the subject of a recently terminated HCM clinical trial known as Liberty-HCM.  The HCM eleclazine study focused on whether the drug would improve symptoms and exercise capacity in patients with HCM by increasing their peak oxygen uptake, resulting in improved VO2 max readings on exercise testing.  The HCM study began enrolling patients in February 2015. Data collection had been scheduled to continue through June 2017. Continue reading “End of the Road for Eleclazine and Liberty HCM Study”