The Phase 3 RESET trial testing the effectiveness and safety of rivipansel (GMI-1070), Pfizer‘s investigational candidate to treat vaso-occlusive crisis (VOC) in hospitalized patients with sickle cell disease (SCD), failed to reach both its primary and secondary goals, top-line study results show.
“We are disappointed with the results, as we have been working in close partnership with the SCD community to advance rivipansel as a potential treatment option for acute VOC,” Brenda Cooperstone, MD, senior vice president and chief development officer, Rare Disease, Pfizer Global Product Development, said in a press release.
“We plan to share the study data at an upcoming scientific meeting as we want to ensure the learnings from this trial help inform future sickle cell programs,” Cooperstone added. “We express our sincere gratitude to everyone who made this study possible, including the study investigators, and in particular, the patients and their families.”
VOC, characterized by a reduced blood flow and ultimate closing of blood vessels due to the adhesion of sickle cells to vessel walls, is a serious complication of SCD linked with severe pain. Currently, VOC symptoms are managed with analgesics, including opioids and non-steroidal anti-inflammatory drugs (NSAIDs), but more effective therapies are needed.
Rivipansel, developed by GlycoMimetics in partnership with Pfizer, was designed to block the activity of cell adhesion molecules called selectins in blood vessels. These molecules are unusually abundant in the blood vessels of SCD patients, leading blood cells to stick to surfaces and to other cells, eventually obstructing blood flow.
Previous clinical data from a Phase 1 trial showed that treatment could decrease several biomarkers of cellular adhesion in SCD patients while maintaining a good safety profile. A follow-up Phase 2 trial confirmed rivipansel’s benefits, and showed that the therapy led to an 83% drop in opioid use for pain management while also reducing the length of hospital stays.
Supported by these data, the RESET trial (NCT02187003) enrolled 345 SCD patients, ages 6 and older, experiencing an VOC requiring hospitalization and intravenous opioid treatment for pain management to further evaluate rivipansel’s therapeutic effects.
Participants were randomized to rivipansel or a placebo delivered intravenously (into the blood) every 12 hours up to a maximum of 15 infusions. They were followed for 35 days after their last dose.
The study’s main goal (primary endpoint) was the change in time to readiness-for-discharge after treatment. Additional (secondary) efficacy endpoints included time-to-discharge, the need for opioids. and the time at which patients no longer required these drugs for pain management.
“We recognize this is a significant setback for the SCD community, who are eagerly awaiting new treatment options, and we share in their disappointment,” said Freda Lewis-Hall, MD, DFAPA, chief patient officer and executive vice president at Pfizer.
“Many of us have witnessed first-hand the devastating impact of SCD on patients and their families, but we have also been moved by their incredible strength and bravery, and we will continue to support this courageous community,” Lewis-Hall added.
Detailed analyses of RESET safety and effectiveness findings, many of which are not yet available, will be presented at future scientific meetings.