Trial of MST-188 in sickle cell disease fails to meet primary endpoint

A randomized phase 3 trial designed to evaluate the investigational drug vepoloxamer failed to meet its primary endpoint of significantly reducing the mean duration of vaso-occlusive crisis in patients with sickle cell disease, according to study results released by the agent’s manufacturer.

Clinical development of vepoloxamer (MST-188, Mast Therapeutics) — which also is being evaluated for patients with chronic heart failure — likely will be terminated, Brian M. Culley, CEO of Mast Therapeutics, said in a press release.

The double blind, placebo-controlled EPIC trial included 388 individuals with sickle cell disease hospitalized for acute pain typical of vaso-occlusive crisis who required treatment with parenteral opioid analgesia.

Study participants ranged in age from 4 to 46 years (mean age, 15 years). The majority (71%) were aged younger than 18 years, and most (61%) were on concurrent hydroxyurea therapy.

Study participants received vepoloxamer or placebo via IV as a 1-hour loading dose infusion (100 mg/kg), followed by a continuous maintenance infusion of 30 mg/kg per hour for at least 12 hours and up to 48 hours.

Efficacy of vepoloxamer for reducing the duration of vaso-occlusive crisis served as the primary study objective. Researchers defined this as the time between randomization to the point when a patient received the last dose of parenteral opioid analgesia prior to hospital discharge.

Secondary efficacy endpoints included re-hospitalization rates for vaso-occlusive crisis within 14 days of initial hospital discharge, as well as occurrence of acute chest syndrome within 120 hours of randomization.

Vepoloxamer did not significantly reduce the mean duration of vaso-occlusive crisis compared with placebo (82 hours vs. 78 hours). Researchers observed no statistically significant differences in secondary efficacy endpoints between treatment groups.

Vepoloxamer appeared well tolerated. Researchers reported no significant differences in treatment-related serious adverse events between treatment groups, and no patients died during the study period.

“We are exceedingly disappointed with these top-line results,” Culley said. “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.”