News | Heart Failure | September 21, 2017

MyoKardia Presents Additional Positive Data From Phase 2 PIONEER-HCM Study at HFSA 2017

New positive data on secondary and exploratory endpoints consistent with previously reported topline results with mavacamten

MyoKardia Presents Additional Positive Data From Phase 2 PIONEER-HCM Study at HFSA 2017

September 21, 2017 — MyoKardia Inc. announced that additional positive data from the first patient cohort of its Phase 2 PIONEER-HCM study were presented at the Heart Failure Society of America (HFSA) 21st Annual Scientific Meeting, Sept. 16-19 in Dallas. PIONEER-HCM was a study of mavacamten in symptomatic, obstructive hypertrophic cardiomyopathy (oHCM) patients.

In an oral presentation as part of the “Big Trials of the Last Year” session at HFSA, Stephen Heitner, M.D., director of the HCM Clinic at Oregon Health and Science University’s Knight Cardiovascular Institute, and the lead investigator in the PIONEER-HCM study, presented new time-series plots of individual patient data on the primary endpoint, post-exercise peak left ventricular outflow tract (LVOT) gradient, and time-series plots of mean data on several additional measures, including resting LVOT gradient and resting left ventricular ejection fraction (LVEF) from baseline to week 12. Additional measures of exercise capacity, functional capacity and symptoms were also presented, as well as data on the safety profile of mavacamten.

MyoKardia initially reported positive topline results from this first patient cohort on Aug. 7, 2017, which met the primary endpoint of change in post-exercise peak LVOT gradient from baseline to week 12 as well as key secondary endpoints, including peak oxygen consumption (peak VO2).

The additional results presented by Heitner indicated that mavacamten treatment led to a meaningful reduction, in the first few weeks of treatment, in resting LVOT gradient with a less pronounced reduction in resting LVEF. The rapid reduction in LVOT gradient, observed in 9 out of 10 patients by week 2, supported the addition of a second, low-dose cohort in the PIONEER-HCM trial.

Furthermore, data following the washout period (from week 12 to week 16) were presented for the following measures: post-exercise peak LVOT gradient, resting LVOT gradient, resting LVEF, dyspnea score, NYHA Functional Class and NT-proBNP. For all of these measures, reversion towards baseline values was observed, on average across the cohort, after mavacamten therapy was discontinued.

“These data strengthen the case, initially seen with the release of the topline results, that mavacamten, by targeting the underlying biomechanical defect of the disease, can affect multiple clinically meaningful metrics that characterize the oHCM disease burden,” said Heitner. “On behalf of the investigators, I am pleased to present these additional data showing the concordant and positive effects of mavacamten, with patients feeling better and displaying improvements in exercise capacity.”

In this first patient cohort of PIONEER-HCM, 11 symptomatic, oHCM patients enrolled and 10 completed the study. Patients were treated with a 10 mg or 15 mg starting daily dose of mavacamten for 12 weeks, followed by a four-week washout phase. In this first cohort, patients were required to discontinue background therapy including beta blockers.

The following table summarizes the baseline characteristics of the 11 patients enrolled in the first cohort of PIONEER-HCM:

Age, years; mean (min-max)
56 (22-70)

Sex, % male

NYHA Functional Class
64% Class II; 36% Class III

History of Paroxysmal Atrial Fibrillation

History of Septal Myectomy

Previous Background Beta Blocker Therapy, Discontinued Prior to Study Start per Protocol

Resting LVEF, %;mean ± SD
70 ± 7.0

Exercise LVEF, %; mean ± SD
76 ± 7.8

Resting LVOT Gradient, mmHg; mean ± SD
68 ± 34.4

Post-Exercise Peak LVOT Gradient, mmHG; mean ± SD
125 ± 60.0

Peak VO2, mL/kg/min; mean ± SD
20.7 ± 7.44

Impact of mavacamten on additional secondary and exploratory endpoints

  • Time-series of mean resting LVOT gradient and mean LVEF were reported today for the first time, showing concordance with data previously reported. Resting LVOT gradient was reduced to 14 ± 24.6 mmHg (mean ± SD) at week 12 from a baseline value of 68 ± 34.4 mmHg. Resting LVEF was reduced to 55 ± 13.1% at week 12 from a baseline value of 70 ± 7.0%.
  • A mean time-series plot of dyspnea numerical rating scale (NRS), a common measure of patient symptoms, was also reported. At week 12, patients achieved an average dyspnea NRS of 1.7 ± 1.8 compared to a baseline of 4.9 ± 1.6 (p=0.002).
  • Furthermore, additional CPET measures of exercise capacity, including VE/VCO2 and circulatory power, also showed similar trends as previously reported data.


Safety overview

  • Mavacamten was generally well-tolerated in this first patient cohort of PIONEER-HCM. As previously reported, one patient experienced a serious adverse event due to a recurrence of atrial fibrillation and elected to stop study drug at week 4.
  • All other adverse events (AEs) were mild to moderate. A majority of AEs were deemed unrelated to study drug. Of these non-serious AEs, the most common observations (defined as three or more events) in this cohort were: headache (4), reduction in ejection fraction (3) and nausea (3). None of these patients with an adverse event report of reduction in ejection fraction had symptoms of decompensated heart failure.
  • Finally, a time-series plot of mean NT-proBNP, a biomarker commonly used to track severity of heart failure, was presented, providing additional support for the favorable safety profile observed.

MyoKardia intends to discuss the mavacamten clinical development plan in an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) and seek feedback on the potential for EXPLORER-HCM, its next study of mavacamten in symptomatic oHCM, to be a pivotal study with peak VO2 as the primary endpoint. The key inclusion and exclusion criteria for EXPLORER-HCM are anticipated to be similar to those for PIONEER-HCM. 

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