September 25, 2017

MyoKardia released additional positive data from the first patient cohort of its phase II PIONEER-HCM study of mavacamten in symptomatic, obstructive hypertrophic cardiomyopathy (oHCM) patients. PIONEER-HCM is an open-label study. oHCM patients with left ventricular ejection fraction (LVEF)=55%, LVOT gradient (resting gradient=30 mmHg, post-exercise peak LVOT gradient=50 mmHg) and New York Heart Association (NYHA) Functional Class=II were treated with mavacamten for 12 weeks, followed by a four-week washout phase. In this first patient cohort of PIONEER-HCM, 11 symptomatic oHCM patients enrolled and 10 completed the study. Patients were treated with a 10mg or 15mg 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. Time-series of mean resting LVOT gradient and mean LVEF were reported 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). All other adverse events (AEs) were mild to moderate. MyoKardia intends to discuss the mavacamten clinical development plan in an end-of-phase II meeting with the FDA and seek feedback on the potential for EXPLORER-HCM, its next study of mavacamten in symptomatic oHCM.

September 6, 2016

CardioCell reported results of a phase IIa trial of intravenous (IV) infusion of ischemia-tolerant allogeneic mesenchymal stem cells (itMSC)in patients with non-ischemic cardiomyopathy. The single-blind, placebo-controlled, crossover study delivered itMSCs to 22 patients with non-ischemic cardiomyopathy and LVEF ≤40%. The study randomized patients into a treatment group and a control group with a 1:1 randomization scheme. CardioCell’s treatment and the placebo were administered intravenously. At 90 days after the first injection, the control group received CardioCell’s treatment, and the original treatment group received the placebo solution. IV itMSC injections exhibit improvements in several clinical-efficacy endpoint measurements, including statistically significant improvement in six-minute walk test (p=0.02), Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary score (p=0.02) and trend to improvement in KCCQ Functional Status score (p=0.06). There was a statistically significant reduction in natural killer cells, the magnitude of which correlated with the magnitude of improvement in left ventricular ejection fraction. In an exploratory data analysis before the 90-day crossover, there was a statistically significant improvement in the left ventricular end systolic and diastolic volumes in the itMSC-treated groups, whereas this was not seen in the placebo-treated group.