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Novel agent reduced time to resolution of vaso-occlusive crisis
NEW ORLEANS — Treatment with the pan-selectin inhibitor GMI 1070 resulted in a clinically meaningful reduction of time to resolution of vaso-occlusive crisis and corresponding opioid use, according to results of a double blind, phase 2 trial presented at the ASH Annual Meeting and Exhibition.
“Considering both the efficacy and the safety data, we feel that these results are strongly in support of proceeding with a phase 3 trial of GMI 1070 to demonstrate statistically significant efficacy,” Marilyn J. Telen, MD, of the department of medicine in the division of hematology at the Duke University Medical Center, said during a press conference. “Further research on this drug will also hopefully bring to clinical practice a new treatment for vaso-occlusive crisis, one that would be directed toward pathophysiologic mechanisms as opposed to symptoms.”
Telen and colleagues evaluated data from 76 patients (59% women) aged 12 to 51 years with sickle cell anemia or HbS beta 0-thalassemia who presented with vaso-occlusive crisis.
Forty-three patients received a loading dose of GMI 1070, followed by up to 14 subsequent doses every 12 hours. The other 33 received placebo.
Resolution of vaso-occlusive crisis — defined as a 1.5 cm sustained decrease from baseline in visual analog scale pain score and transition to oral analgesia; documented readiness; or order for discharge — served as the primary efficacy endpoint.
Cumulative opioid use and adverse events served as secondary endpoints.
All patients reached the primary endpoint. Fifty-eight patients continued the study drug until criteria for resolution of vaso-occlusive crisis was met or the maximum number of doses were administered. Eighteen patients discontinued treatment due to adverse events, a lack of improvement at day 5 or other reasons.
Patients assigned to GMI 1070 demonstrated markedly reduced mean time to resolution of vaso-occlusive crisis than those assigned to placebo (103.6 hours ± 20.9 vs. 144.6 hours ± 23.5; P=.192).
Kaplan-Meier analysis showed median time to resolution with GMI 1070 was 69.6 hours (95% CI, 44.3-115.5) vs. 132.9 hours (95% CI, 67-164.2) with placebo (P=.187). Researchers observed similar reductions in time to discharge between all age and dose groups.
Pediatric patients assigned to GMI 1070 demonstrated a significant decrease in time to transition to oral pain medication than those assigned to placebo (87.8 hours; P=.037).
Median time to discharge was shorter with GMI 1070 (72.2 hours; 95% CI, 59.9-121) than with placebo (156.1 hours; 95% CI, 75.4-185.8; P=.092).
Patients treated with GMI 1070 demonstrated an 83% reduction in mean cumulative IV opioid analgesic use (P=.01).
Incidence and grade of adverse events did not significantly differ between study arms.
“If this drug continues to demonstrate efficacy in our ongoing studies, it would be the first to actually interrupt the mechanism of vaso-occlusive crisis,” Telen said. “This would signal a major breakthrough since, even though we have increased our understanding of how these debilitating crises develop, we have not been able to intervene once they happen. This potential new drug would change that.”
For more information:
Telen MJ. Abstract #776. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2013; New Orleans.
Disclosure: The researchers report research funding from, consultant, employment or committee roles with, and equity ownership in Dilaforette, Emmaus Inc., GlycoMimetics, Novella Clinical, Pfizer and Rho Inc.