For theintent-to-treat population, there were no statistically significant differences at 16 weeks between active and placebo groups in exploratory endpoints, with the exception of levels of the biomarker NT-proBNP, which were markedly reduced in patients receiving mavacamten (p=0.004) across both treatment cohorts, as compared to the placebo group. NT-proBNP is a well-established biomarker of cardiac wall stress, and elevated NT-proBNP levels are associated with reductions in the rate of heart failure-related death or hospitalization, progression toend-stage disease and stroke.
In apre-specified subgroup representing patients believed to be at higher risk of morbidity and mortality, meaningful trends suggesting clinical benefit were observed for patients on treatment versus placebo across multiple endpoints of symptoms, function, biomarkers of cardiac stress and diastolic compliance.
Additionally, similar trends were observed in a subgroup of patients with elevated cardiac filling pressures (measured by E/e’), suggesting improvement driven by reduced left ventricular pressure, consistent with mavacamten’s targeted mechanism.
“The topline data reported today are important in the advancement of mavacamten across multiple indications. The safety and tolerability data, evidence of mavacamten’s beneficial impact on parameters of diastolic function, and placebo response observations confirm our assumptions and increase our confidence in theEXPLORER-HCM Phase 3 clinical study of mavacamten in obstructive HCM,” said Tassos Gianakakos, Chief Executive Officer of MyoKardia.
AboutMAVERICK-HCM
The Phase 2MAVERICK-HCM trial was designed to assess the safety and tolerability of a range of exposures over 16 weeks of treatment in patients with symptomatic,non-obstructive HCM. All study participants were required to be diagnosed withnon-obstructive HCM, with left ventricular wall thickness either >15mm or >13mm with a family history of HCM, New York Heart Association (NYHA) classifications of Class II or III, and NT-proBNP levels of greater than 300 pg/mL at rest. Baseline characteristics, such as age, weight, gender, pathogenic mutation status, background beta blocker use, NYHA classification and exercise capacity were evenly distributed between active and placebo arms.
A total of 59 participants were enrolled in the study and randomized into one of three groups to receive once-daily doses of mavacamten or placebo. The active mavacamten treatment arms were designed to assess a range of drug concentrations around target levels of 200ng/mL and 500ng/mL. All participants in the active treatment arms began the study receiving 5mg doses of mavacamten. At Week 4, pharmacokinetic (PK) assessments were conducted and doses were adjusted in a blinded fashion per the protocol based on the participant’s assigned cohort. Following the16-week treatment period, participants were monitored for an additional eight weeks and became eligible to participate in MyoKardia’s MAVA Long-Term Extension (LTE) study.
Conference Call and Webcast
MyoKardia management will host a conference call and live audio webcast this morning at 8:30 a.m. ET / 5:30 a.m. PT to review the topline data reported today from the MAVERICK Phase 2 clinical trial and new data from thePIONEER-OLE study. Investors and analysts are invited to participate in the call by dialing844-494-0913 (U.S.) or508-637-5584 using the conference ID 3177984. The webcast may be accessed live on the Investor Relations section of the MyoKardia website. A replay of the webcast will be available on MyoKardia’s website for 90 days following the call.
AboutNon-obstructive HCM
Hypertrophic cardiomyopathy is the most common genetic form of heart disease, affecting an estimated one in every 500 people worldwide. There are two main forms of HCM, obstructive HCM andnon-obstructive HCM, which often share the same underlying genetic defects in the sarcomere that results in hypercontractility. Innon-obstructive HCM, the heart contracts excessively and the left ventricle becomes abnormally thick, restricting the ability of the heart to relax and fill or pump to meet the body’s needs, but no physical obstruction is present in the outflow tract of the left ventricle.Non-obstructive HCM affects an estimatedone-third of all HCM patients and presents unique treatment challenges. Patients may progress to a more advanced state of disease than those with obstructive disease before being diagnosed, and there are no approved treatment options available. Asnon-obstructive HCM progresses, symptoms begin to resemble those of a congestive heart failure patient and heart transplantation may become the only viable treatment option.
About Mavacamten(MYK-461)
Mavacamten is a novel, oral, allosteric inhibitor of cardiac myosin being developed for the treatment of hypertrophic cardiomyopathy (HCM). Mavacamten is intended to reduce cardiac muscle contractility by inhibiting the excessive myosin-actin cross-bridge formation that underlies the excessive contractility, left ventricular hypertrophy and reduced compliance characteristic of HCM. MyoKardia is currently evaluating mavacamten in multiple clinical trials for the treatment of obstructive andnon-obstructive HCM. The pivotal Phase 3 clinical trial, known asEXPLORER-HCM, is being conducted in patients with symptomatic, obstructive HCM and MyoKardia anticipates data from this program in Q2’2020. Two long-termfollow-up studies are also ongoing, the PIONEER open-label extension study of obstructive HCM patients from MyoKardia’s Phase 2 PIONEER trial and theMAVA-LTE, an extension study for patients who have completed eitherEXPLORER-HCM orMAVERICK-HCM, the company’s Phase 2 clinical trial of symptomaticnon-obstructive HCM patients. In April 2016, the U.S. FDA granted Orphan Drug Designation for mavacamten for the treatment of symptomatic obstructive HCM.
