Success reported in Phase 3 study into sickle cell disease

SAN DIEGO  — Mast Therapeutics, Inc. , a biopharmaceutical company developing novel, clinical-stage therapies for sickle cell disease and heart failure, today reported top-line results from EPIC, a Phase 3 clinical study of its investigational new drug vepoloxamer (also known as MST-188) for the treatment of individuals with sickle cell disease experiencing vaso-occlusive crisis (VOC).  The study did not meet its primary efficacy endpoint of demonstrating a statistically significant reduction in the mean duration of VOC (82 hours in the vepoloxamer group compared to 78 hours in the placebo group in the intent-to-treat population (p=0.09)).  There were no statistically significant differences between treatment groups in the intent-to-treat population across the two secondary efficacy endpoints, rate of re-hospitalization for VOC and the occurrence of acute chest syndrome. Consistent with previously conducted studies, vepoloxamer was generally well tolerated with no statistically significant differences in treatment-related serious adverse events in the vepoloxamer group compared to the placebo group. No deaths occurred on the study.

“We are exceedingly disappointed with these top-line results. While clearly not the outcome we wanted, we believe the insights and data from the largest placebo-controlled clinical trial ever completed in sickle cell disease will substantially advance the understanding of vaso-occlusive crisis and the still maturing clinical science necessary to support the development of new therapeutics for this debilitating disease,” stated Brian M. Culley, the Company’s Chief Executive Officer. “We wish to reiterate our sincere appreciation for all of the patients, caregivers, and others who aided us in conducting this informative study.”

Top-line Data

“These analyses are limited to just top-line data, so in the coming weeks the Company intends to review the full data set from EPIC. In addition, we plan to perform an interim analysis of the ongoing heart failure trial of vepoloxamer. However, based on the data we’ve seen to date, we expect we will terminate all clinical development of vepoloxamer. Consequently, while we evaluate our options, we intend to significantly and immediately reduce our operating expenses and continue our efforts with AIR001, our lead asset in heart failure with preserved ejection fraction, which currently is the subject of a 100-patient phase 2 study expected to complete enrollment by the end of 2017,” continued Mr. Culley.

About the EPIC Study
The EPIC study was a randomized, double-blind, two-arm, placebo-controlled, Phase 3 clinical trial of vepoloxamer in individuals with sickle cell disease hospitalized for acute pain typical of vaso-occlusive crisis who required treatment with parenteral opioid analgesia. The primary objective of the study was to evaluate the efficacy of vepoloxamer in reducing the duration of vaso-occlusive crisis, with the duration of crisis measured from the time of randomization to the time at which the patient received the last dose of parenteral opioid analgesia for the treatment of vaso-occlusive crisis prior to hospital discharge.  Vepoloxamer or placebo (0.45% saline) was administered intravenously as a 1 hour loading dose infusion (100 mg/kg), immediately followed by a continuous maintenance infusion (30 mg/kg/hr) for at least 12 hours and up to 48 hours.  Randomization was stratified by age (≥4 to <16 years or ≥16 to ≤65 years), use of hydroxyurea (yes or no), and pain score (measured using the Wong-Baker FACES® Pain Rating Scale at time of randomization: <8 or ≥8). The study was 90% powered to detect a 17% (16-hour) difference in treatment arms, with a statistical significance level of p=0.05 (assuming an average crisis duration of 96 hours in the control arm and a coefficient of variation > 50%).  Secondary efficacy endpoints were to compare the rates of re-hospitalization for vaso-occlusive crisis within 14 days of initial hospital discharge and the occurrence of acute chest syndrome within 120 hours of randomization between the treatment and control groups.

A total of 388 patients, ages four to 46, were randomized in EPIC.  More than 75 study sites in 14 countries participated.  The average age was 15 years.  Patients under age 18 accounted for approximately 71% of total subjects.  Approximately 61% of patients were concurrently on hydroxyurea therapy.  – PRNewswire

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