MyoKardia announces pipeline updates at its R&D Day
MyoKardia announced an update on its clinical-stage and emerging pipeline at its R&D Day. MyoKardia shared interim data from the PIONEER Open-Label Extension, or OLE, study of mavacamten for the treatment of symptomatic oHCM. Twelve of twenty patients with oHCM who previously completed MyoKardia's Phase 2 PIONEER-HCM trial have enrolled in PIONEER-OLE, and seven patients have completed a twelve-week assessment. Despite treatment with therapies such as beta blockers and calcium channel blockers, patients entered PIONEER-OLE with significant left ventricular outflow tract, or LVOT, obstruction. Following resumed mavacamten treatment with individualized dosing, evaluable patients in PIONEER-OLE achieved a statistically significant reduction in LVOT obstruction, to a mean provoked gradient of 22.3mmHg. For reference, LVOT obstruction is defined as a gradient of 30.0mmHg or greater at rest and a gradient of greater than 50.0mmHg is considered to be hemodynamically significant. In MyoKardia's Phase 2 PIONEER-HCM clinical trial of mavacamten, reductions in LVOT obstruction correlated to improvements in patients' symptoms and exercise capacity. All patients maintained ejection fractions well in the normal range of greater than 50%. There have been no significant adverse events reported. The longest duration of treatment thus far has been 25 weeks. MyoKardia plans to present additional data from PIONEER-OLE in Q1 of 2019, including gradient and ejection fraction data from longer term exposures, NT-proBNP and NYHA functional classification changes. MyoKardia announced the expansion of its pipeline with MYK-224, a second HCM-targeted candidate with differentiated pharmaceutical properties. Like mavacamten, MYK-224 is designed to correct excess contractility and address impaired diastolic function, without affecting myosin-actin cross-bridge kinetics or inducing an increase in calcium transient or energy burden. MYK-224 has been optimized to enable rapid dose adjustment and simplify dose finding in patients. MyoKardia plans to initiate a Phase 1 clinical trial in 2019 followed by a Phase 2a trial in 2020 addressing a complementary HCM population to mavacamten. MyoKardia shared preclinical data from its emerging LUS-1 program, a class of agents targeted at improving diastolic compliance, or the ability of the heart to relax and fill. Experience in preclinical studies and observations from clinical trials of mavacamten suggests that it may improve diastolic function and compliance. Building on these data, MyoKardia has discovered compounds that improve diastolic compliance with minimal impact on contractility. Preclinical data were shared that demonstrate that MyoKardia's proprietary agents successfully uncouple contractility inhibition from improved diastolic compliance, with a net positive impact on stroke volume. MyoKardia plans to share more mavacamten clinical data relating to its potential diastolic benefits at the upcoming American Heart Association Annual Meeting in November and will disclose additional preclinical data in relevant disease models for its LUS-1 program in 2019.