When Stanford biochemist Jim Spudich settled down in bed with a book recommended by his wife, he had no idea that the book would inspire one of the biggest discoveries of his career. Spudich drifted off to sleep while reading The Haunted Mesa, a science fiction novel by Louis L’Amour. His scientific discovery was based on an image he saw in his dreams when the image of a mesa morphed into a myosin molecule.
Myosins are proteins that make the contraction of heart muscle possible. In hypertrophic cardiomyopathy, these proteins work too well, causing a heartbeat that is too strong.
The mesa in the book inspired Spudich to look at the head of the myosin. His previous research had focused on random locations along the entire length of the myosin.
Spudich’s groundbreaking work ultimately led to current clinical trials of the drug mavacamten which is being developed by the San Francisco biotech company MyoKardia.
This article tells the whole story of the beginnings of this groundbreaking research.
This week, MyoKardia announced positive data on its experimental drug for HCM, mavacamten (formerly known as MYK-461), for obstructive HCM.
After 6 months on the drug, of the 13 patients enrolled in the open label extension to the Pioneer study, NYHA Class improved in 8 of 10 patients, while 7 of the 8 patients were considered asymptomatic by the end of the study.
In addition to seeing an improvement in symptoms, patients also showed improvement to certain markers of cardiac function including left ventricular filling pressure,
NT-proBNP, a marker of cardiac wall stress, and left atrial volume index. Ejection fractions remained within normal levels for all patients in the study.
The complete results of this study will be presented by Oregon Health & Science University’s Dr. Steven Heitner at next weekend’s meeting of the American College of Cardiology in New Orleans.
DISCLOSURES: HCMBEAT HAS RECEIVED 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.
MyoKardia is collaborating with 23andMe, a genetic testing company which provides ancestry and health information directly to consumers, to create an online patient community intended to advance research efforts related to hypertrophic cardiomyopathy. The companies plan to allow 23andMe customers access to the latest information about HCM, as well as the opportunity to participate in research.
The companies will use a custom designed survey to collect baseline and follow-up data from HCM patients. They are hopeful that this collaboration will yield unique insights into HCM.
Research findings gained through the collaboration will be shared with HCM patients through the 23andMe platform. Currently more than 6,000 HCM patients are customers of 23andMe
More details of the collaboration can be found:
Press release from MyoKardia and 23andMe
DISCLOSURES: HCMBeat has received 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.
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.
MyoKardia, a San Francisco biotech company currently in clinical trials on a HCM drug called Mavacamten, has come up with a way to spot HOCM simply by using a wristband fitness monitor. The wristband works through the use of optical biosensors which monitor arterial pulse waves.
During MyoKardia’s trials, the bracelet biosensors were used on HOCM patients and non-affected controls. The algorithm was able to distinguish HOCM patients from unaffected individuals more than 95% of the time, suggesting that a non-invasive way to screen for HOCM may not be too far in the future.
The linked article at Medgadget contains an interview with MyoKardia’s Dr. Robert McDowell, MyoKardia’s Chief Scientific Officer, and Dr. Eric Green, MyoKardia’s Senior Director of Translational Research with more on the happenings at MyoKardia.
A few months ago, HCMBeat featured this post about HCM Care, a new educational website and downloadable app for HCM patients and their families, featuring essential information for patients trying to understand their HCM diagnosis, explained in written and video formats. HCM Care also provides useful information about genetic testing and family screening for their family members.
Dr. Andrew Wang of Duke University’s HCM Clinic in Durham, N.C., developed HCM Care along with 8 other HCM specialists from 6 hospitals, including Mayo Clinic, Cleveland Clinic and Tufts Medical Center. Funding and support for the project were provided by MyoKardia, a San Francisco biotech company engaged in the development of a precision medicine approach to the treatment of genetic cardiomyopathies. Their HCM medication, MYK-461, is currently in clinical trials in the U.S.
Cynthia Burstein Waldman of HCM Beat had the opportunity via email to talk with Dr. Wang about his HCM practice and his involvement with the development of HCM Care. What follows is their written correspondence, edited for clarity:
Continue reading “A Conversation with Duke’s Dr. Andrew Wang – Creator of the HCM Care App”
NOTE: As of July, 2018 the website and app have been updated to include even more information for HCM patients. Check it out.
Have you heard that there is a new online educational resource about HCM? Check out HCM Care.com, an informational website about HCM developed by MyoKardia in partnership with Duke Clinical Research Institute.
This website features general information about HCM including diagnosis, testing, treatment, lifestyle, genetics and family screening. It is also available as a FREE downloadable app for both Apple and Android operating systems.
Click here to find on iTunes and Google Play.
HCMCare features video clips from the following physicians:
- Dr. James Daubert from Duke University Medical Center
- Dr. Milind Desai from Cleveland Clinic
- Dr. Carolyn Ho from Brigham and Women’s Hospital
- Dr. Martin Maron from Tufts Medical Center
- Dr. Andrew Wang from Duke University Medical Center
Be sure to check out HCMCare, as well as many other helpful resources which are listed on HCMBeat’s Resources page.
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.
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”