MST-188 Trial Fails to Achieve Goal as Sickle Cell Disease Therapy

Mast Therpeutics has announced that the clinical development of Vepoloxamer (MST-188) is likely to be terminated. Results from a Phase 3 clinical trial evaluating the investigational drug in patients with sickle cell disease (SCD) failed to meet its primary goal.

Brian M. Culley, Mast Therapeutics’ chief executive officer, announced in a press release that  Velopoxamer didn’t meet its primary endpoint of significantly reducing the mean duration of vaso-occlusive crisis (VOC) in SCD patients.

“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,” he said.

The Phase 3, double-blind, placebo-controlled EPIC clinical trial (NCT01737814) included 388 SCD patients who were hospitalized for acute pain typical of VOC and required treatment with parenteral opioid analgesia.

Participants ranged in age from 4 to 46 years old, with a mean age of 15. Most patients were younger than 18 (71%) and 61% were on concurrent hydroxyurea therapy. Participants were given vepoloxamer or placebo intravenously as a one-hour loading dose infusion (100mg/kg), followed by a continuous maintenance infusion of 30mg/kg per hour for a minimum of 12 hours and a maximum of 48 hours.

The primary study objective was to measure the efficacy of Vepoloxamer in reducing VOC’s duration. The study’s investigators defined this as the time between randomization to the point when a patient received the last dose of parenteral opioid analgesia before hospital discharge.

The study’s secondary efficacy endpoints included re-hospitalization rates for VOC within 14 days of initial hospital discharge, as well as reports of acute chest syndrome within 120 hours after randomization.

The trial results indicate that Vepoloxamer did not significantly reduce the mean duration of VOC vs. placebo (82 hours vs. 78 hours). In addition, no statistically significant differences in secondary efficacy endpoints were observed between treatment groups.

The investigational drug was found to be well-tolerated, however, with no significant differences in treatment-related serious adverse reactions reported in either treatment group, and no patients died during the trial, according to the press release.