Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use.
Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and abrogating VOC. We studied GMI-1070 in a prospective multicenter, randomized, placebo-controlled, double-blind, phase 2 study of 76 SCD patients with VOC. Study drug (GMI-1070 or placebo) was given every 12 hours for up to 15 doses. Other treatment was per institutional standard of care. All subjects reached the composite primary end point of resolution of VOC. Although time to reach the composite primary end point was not statistically different between the groups, clinically meaningful reductions in mean and median times to VOC resolution of 41 and 63 hours (28% and 48%, P = .19 for both) were observed in the active treatment group vs the placebo group. As a secondary end point, GMI-1070 appeared safe in acute vaso-occlusion, and adverse events were not different in the two arms. Also in secondary analyses, mean cumulative IV opioid analgesic use was reduced by 83% with GMI-1070 vs placebo (P = .010). These results support a phase 3 study of GMI-1070 (now rivipansel) for SCD VOC. This trial was registered at www.clinicaltrials.gov as #NCT01119833.
Department of Medicine, Division of Hematology, Duke University, Durham, NC;
Marilyn J
MJ
Telen
Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis Medical Center and VA Northern California Health Care System, Sacramento, CA;
Ted
T
Wun
Department of Pediatric Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX;
Timothy L
TL
McCavit
Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh, Pittsburgh, PA;
Laura M
LM
De Castro
Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA;
Lakshmanan
L
Krishnamurti
Department of Medicine, Division of Hematology, Johns Hopkins School of Medicine, Baltimore, MD;
Sophie
S
Lanzkron
Department of Pediatrics, University of Illinois, Chicago, IL;
Lewis L
LL
Hsu
Division of General Internal Medicine, Virginia Commonwealth University, Richmond, VA;
Wally R
WR
Smith
Rho, Inc., Chapel Hill, NC; and.
Seungshin
S
Rhee
GlycoMimetics, Inc., Gaithersburg, MD.
John L
JL
Magnani
GlycoMimetics, Inc., Gaithersburg, MD.
Helen
H
Thackray
D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006017:Glycolipids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014652:Vascular Diseases / Q000150:complications* / Q000188:drug therapy*; D055815:Young Adult
D000700:Analgesics; D000701:Analgesics, Opioid; D006017:Glycolipids; C553182:rivipansel