Dr. Harry Lever Speaks Out About Problems With Generic Drugs

This Medscape article highlights the extraordinary efforts of Dr. Harry Lever, Director of the Cleveland Clinic’s Hypertrophic Cardiomyopathy Center, in educating patients and physicians alike about quality issues with generic drugs.  Dr. Lever has been instrumental in publicizing the fact that generic drugs are NOT always the same as their name brand counterparts, and that foreign generics are not put through the same level of scrutiny as drugs in the U.S.

Journalist Katherine Eban who recently published a book entitled Bottle of Lies: The Inside Story of the Generic Drug Boom is quoted in the Medscape article and has this to say:

“Dr Lever has been tireless in raising the alarm publicly, and with the FDA, about those generics that he felt were actively harming his patients, and remarkably, in case after case, he has been correct in his clinical judgments, and often far ahead of the FDA in detecting problematic drugs. His patients, many of whom I interviewed for Bottle of Lies, are grateful to him, as we all should be.”

And, in June of 2014, Dr. Lever discussed quality control issues with generic Toprol and was interviewed for this article featured in the New York Times.  Dr. Lever was alerted to the issue when many of his patients complained of a return of symptoms after having switching from the brand drug Toprol to one of the many generic formulations of the drug.

So, after all of these experiences, what does Dr. Lever himself do when prescribing drugs for his patients?  As the Medscape article goes on to say:

Despite all his misgivings, Lever still prescribes generic drugs. Brand name drugs are simply too expensive, or patients’ insurers will cover only generics. However, he does try to specify that the generics come from American companies that manufacture in this country under the eye of the FDA.

HCMBeat would like to join with Dr. Lever’s patients and thank him for his tireless efforts on behalf of HCM patients.  It is greatly appreciated.

Dr. Srihari Naidu Talks About HCM Medical Education

Recently, Cynthia Waldman of HCMBeat corresponded with Dr. Srihari S. Naidu of Westchester Medical Center the second edition of an HCM textbook he recently edited, as well as about medical education surrounding hypertrophic cardiomyopathy in general. What follows is a transcript of their correspondence (which has been slightly edited for readability).

Continue reading “Dr. Srihari Naidu Talks About HCM Medical Education”

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.

Should Children from HCM Families be Screened Earlier?

A recent study by doctors at Toronto’s Hospital for Sick Children suggests that current screening guidelines for children from HCM families are inadequate and should instead recommend earlier screening exams. In the U.S., screening begins at age 12 pursuant to American College of Cardiology (ACC)/American Heart Association (AHA) guidelines.  In Europe, screening begins at age 10 pursuant to the European Society of Cardiology (ESC) guidelines.

In particular, the doctors found that out of 524 children who underwent
family screening prior to age 18, 9.9% showed evidence of HCM at first screening and only 1.1% of these children were symptomatic. An additional 28 (5.4%) children developed HCM over 3 years of follow-up, while 41% of major cardiovascular events [death, sudden cardiac death, or need for major interventions such as myectomy, ICD implantation, or heart transplant] occurred in children before the age of 10 year. Therefore, the doctors suggest that certain children appear to be at elevated risk and should be followed from earlier ages.

In particular, the study showed that children at greatest risk are:

  • male
  • have a pathogenic genetic mutations in MYH7 or MYBCP3
  • Have a family history of sudden cardiac death

A companion editorial by Dr. Christopher Semsarian of the University of Sydney in Australia and Dr. Carolyn Ho of the Brigham and Women’s Hospital in Boston points out that even under current guidelines, while screening is optional before age 12 (2011 ACC/AHA Guidelines) or age 10 (2014 ESC Guidelines), screening should still be considered if there is a particularly malignant family history, the child is an athlete or if there are symptoms or other indications of disease.

Semsarian and Ho note that even though screening tests (echocardiograms and EKGs) and non-invasive, there can be both monetary and emotional costs to the family resulting from screening. Hence, they recommend individualization in screening as opposed to a blanket rule; especially given that information relating to genetic status, gender and family history are easily available.  Each family situation should be assessed individually, taking into consideration their own set of unique risk factors and their tolerance for risk.

Editor’s Note:  HCMBeat recently highlighted this study from the U.K. which similarly concluded that the age of screening children in HCM families should be lowered.

 

 

 

Scientists Get $10 Million Grant to Develop HCM Treatments

A group of scientists led by Stanford University’s Dr. James Spudich, working together with researchers from the University of California-Santa Barbara, the University of Washington and the Institut Curie in Paris, has recently been awarded a $10 million grant by the National Institute of General Medical Sciences to develop novel treatments for hypertrophic cardiomyopathy (HCM). 

The researchers hope that the added resources from this grant will help them find ways to correct pathological heart protein changes they believe to be at the root of HCM. The team then plans to partner with pharmaceutical companies to develop more personalized approaches to HCM treatment.

Dr. Spudich has long been involved in HCM research and has been a founder of two separate companies which are currently engaged in drug trials for potential HCM treatments:  MyoKardia and Cytokinetics.

A story about Dr. Spudich and the inspiration for his work was featured in this recent post on HCMBeat.

Docs Reliably Identify HCM Patients in Need of ICDs

According to a paper published last week in JAMA Cardiology, doctors at Tufts University’s HCM Center have been able to identify 95% of their patients at high risk of sudden cardiac death (SCD) from HCM.  Tufts applied an updated and modified version of the risk factors enumerated in the American College of Cardiology/American Heart Association Guidelines promulgated  in 2011.

Continue reading “Docs Reliably Identify HCM Patients in Need of ICDs”

Wall Street Journal Highlights Risks in Genetic Testing

This story in the Wall Street Journal about genetic testing shows the speed of changes in the medical community’s understanding of how and whether certain genes cause hereditary disease.

The article quoted Dr. Jodie Ingles, a geneticist from the University of Sydney in Australia who specializes in HCM and has published a recent article on the subject.  Dr. Ingles said that 22 out of 33 genes comprising a genetic testing panel commonly used to test for HCM had either limited or no evidence of being disease causative.

Continue reading “Wall Street Journal Highlights Risks in Genetic Testing”

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”

Are Your Genetic Test Results Valid?

A recent study by several HCM genetics researchers around the globe, led by Australia’s Dr. Jodie Inglesfound that 2/3 of genetic mutations previously reported to patients as HCM causative may actually NOT trigger HCM.

Continue reading “Are Your Genetic Test Results Valid?”

The High Hanging Fruit: Treatment for Non-Obstructive HCM – Commentary by Dr. Sharlene Day

A recent study conducted in the U.K. evaluated whether the anti-anginal drug trimetazidine would improve symptoms and exercise capacity for those patients with non-obstructive hypertrophic cardiomyopathy. 

Unfortunately, this study which was conducted by Dr. Perry Elliott and his colleagues at University College London, found that trimetatazidine did not improve exercise capacity in these patients. Following the results of this study, trimetazidine will now join ranolazine and spironolactone in the compost heap of drugs which tried and failed to improve HCM symptoms.  While a third drug, perhexiline, was found to improve symptoms for non-obstructive HCM, its limitations, including potentially serious side effects, stand in the way of its common usage.

In a companion editorial to this study entitled “Non-Obstructive Hypertrophic Cardiomyopathy-the High Hanging Fruit,” Dr. Sharlene Day of the University of Michigan’s HCM Center discusses the difficulties seen in drug trials related to non-obstructive HCM.

Continue reading “The High Hanging Fruit: Treatment for Non-Obstructive HCM – Commentary by Dr. Sharlene Day”