Currently Viewing:
American Heart Association Scientific Sessions 2019
Kiersten Combs Discusses Findings of the DAPA-HF Study in Population Without Diabetes
November 17, 2019
Dr Jay Edelberg Outlines the Clinical Burdens and Treatment Options for Hypertrophic Cardiomyopathy
November 17, 2019
Details of DAPA-HF Results Point to Dapagliflozin for Some Heart Failure Patients Without Diabetes
November 17, 2019
In Stable Heart Disease, Study Finds Stents Might Be No Better Than Drugs
November 17, 2019
Dapagliflozin Meets Quality-of-Life Marks, Efficacy Among Seniors, Data Show
November 17, 2019
From Self-Reporting Accuracy to Therapy Access: AHA Posters Cover Issues in Disparities
November 18, 2019
Dr John Pfeifer Outlines Necessary Steps for Preventive Action in Patients With Atrial Fibrillation
November 18, 2019
Sara Levintow Analyzes 2013 ACC/AHA Cholesterol Guidelines in Relation to Trends in US Lipid Testing
November 18, 2019
Plaques May Be Key to Vascepa's Role in Preventing CV Events
November 18, 2019
Currently Reading
48-Week Results for Mavacamten Draw Crowd at AHA Session
November 19, 2019
Dr Stephen Heitner Details the Significance of the PIONEER-OLE Study in Treating Obstructive HCM
November 19, 2019
Dr Stephen Heitner Outlines the Next Steps After MAVERICK-HCM Study Findings
November 21, 2019
Dr Stephen Voyce Details Innovations and Preventive Strategies in Detection of Atrial Fibrillation
November 24, 2019
Dr Brent Williams Discusses Study Findings on Detection of Atrial Fibrillation
November 27, 2019
Dr Brandon Fornwalt Discusses the Preventive Efficacy of AI in Monitoring for Atrial Fibrillation
November 30, 2019
Dr Douglas Losordo Discusses the Evolution and Importance of CD34+ Treatment in Patients With CMD
December 04, 2019
Dr Brian Ghoshhajra Details the Significance of the PDS-2 System in Affecting Progression of HoFH
December 05, 2019
Dr Roland Chen Outlines the GUARD-AF Trial as a Preventive Mechanism in Reducing Risk of Stroke
December 06, 2019
Dr Darryl Sleep: Identifying and Treating Elevated LDL-C in Patients Can Mitigate Heart Attack Risk
December 06, 2019

48-Week Results for Mavacamten Draw Crowd at AHA Session

Mary Caffrey
Mavacamten is a first-in-class small-molecule therapy that reduces the contractility of cardiac muscles by binding with myosin, a protein involved in muscle contraction that is often affected by a gene mutation in hypertrophic cardiomyopathy.
One of the last events of the 2019 American Heart Association Scientific Sessions had no empty seats and dozens left standing to hear about mavacamten after recent news that a treatment might be near for patients who suffer from dangerous thickening of the heart muscle.

A week prior, MyoKardia had released encouraging results from PIONEER-OLE, an open-label extension of its original phase 2 study. As lead investigator Stephen B. Heitner, MD, explained Monday during the AHA’s final “rapid fire” abstract session, the 13 patients who continued to the 48-week mark are seeing a reduction in symptoms of obstructive hypertrophic cardiomyopathy (HCM), and the treatment is measurably undoing damage. Echocardiography shows interventricular septal thickness reduced by an average of 3.2 mm, and 1.3 mm of that reduction came after the 36-week mark.

Heitner, director of the Hypertrophic Cardiomyopathy Clinic at the Oregon Health and Sciences University Knight Cardiovascular Institute, explained that mavacamten is a first-in-class small-molecule therapy that reduces the contractility of cardiac muscles by binding with myosin, a protein involved in muscle contraction that is often affected by a gene mutation in HCM.

In HCM, the heart muscle thickens or becomes “hypertrophied” without any apparent cause, although there’s been extensive work in recent years to understand the genetic causes of many cases. HCM may not show symptoms for years, and when they emerge as tiredness or shortness of breath, cardiomyopathy might not be an obvious culprit. But if undetected, HCM can cause sudden cardiac death.

In most cases of HCM, as blood exits the heart through the left ventricle, the left ventricular outflow tract (LVOT) becomes blocked by the enlarged heart muscle, which restricts blood flow to the body; this is known as obstructive HCM. In remaining cases, called non-obstructive HCM, the disease is marked by diastolic impairment and can still limit daily activities.

The 13 patients (9 male, mean age 57.8 years) in PIONEER-OLE were among the 21 who took part in the earlier phase 2 PIONEER study, Heitner said; those results were reported earlier this year in Annals of Internal Medicine.

“We employed a [pharmacokinetic]-directed dosing strategy individual to each patient,” he said, with doses starting at 5 mg and titrated up to maximum of 15 mg per day. The only major change from the early phase 2 study was that patients were permitted to be on beta blockers.

Results at 48 weeks were as follows:
  • The LVOT gradient, which measures obstruction of the left ventricle, decreased from an average of 89.9 mmHg at baseline to 21.4 mmHg, with statistical significance among 12 patients. Heitner noted that the study had statistical significance at 36 weeks; the fact that the data missed at 48 weeks “needs to be viewed with a pinch of salt, because there are only 13 patients in the study.”
  • Resting LVOT fell from 67.3 mmHg at baseline to 15.3 mmHg at week 48; every patient achieved a level below 55 mmHg, which is the threshold for surgical intervention. Thus, mavacamten has the potential to eliminate the need for costly and risky surgeries in patients whose disease has progressed.
  • NT-proBNP, a marker of cardiac wall stress, decreased from 1836 pg/mL to 206 pg/mL at week 48.
  • New York Heart Association classifications were remeasured at weeks 24 and 48, and 9 of the 12 patients evaluated achieved Class I status.
Best of all, Heitner said, “Patients felt better.” This was confirmed with a Kansas City Cardiomyopathy Questionnaire, which showed an improvement of 14 points on a scale of 0 to 100; an improvement of 6 points is considered clinically significant.

Some patients have been on mavacamten for almost 18 months, and thus far, the drug is very well tolerated. At 48 weeks, there were 64 adverse events (AEs) of which 4 were serious, but Heitner said it was not felt that any were related to the study drug.

The effects are “persistent and durable,” he said, and echocardiography shows that the improvements in the heart muscle are occurring over time without damage to the heart wall. “The data suggest that mavacamten has a favorable impact on the cardiac structure,” Heitner said.

Enrollment of 251 patients in EXPLORER, a phase 3 trial, was complete in July 2019, and topline results are expected in the second quarter of 2020, according to MyoKardia’s recent third-quarter financial results.

Reference

Heitner SB, Lester S, Wang A, et al. Precision pharmacological treatment for obstructive hypertrophic cardiomyopathy with mavacamten: one-year results from PIONEER-OLE. Presented at the 2019 American Heart Association Scientific Sessions, Philadelphia, Pennsylvania; November 18, 2019. Abstract RF295.

 
Copyright AJMC 2006-2019 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
x
Welcome the the new and improved AJMC.com, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up