GMI-1070 to Treat Sickle Cell Disease

New Orleans—Patients with sickle cell disease who received GMI-1070 after hospitalization had faster vaso-occlusive crisis (VOC) resolution and a shorter length of hospital stay compared with a group taking placebo, according to a randomized, prospective, multicenter, placebo controlled, double-blind, phase 2 study.

Marilyn J. Telen, MD, lead author of the trial, said that the difference was not statistically significant because of a larger than expected variability within the groups. Dr. Telen presented the results during an oral abstract session at the ASH meeting. GlycoMimetics, Inc., the manufacturer of GMI-1070, supported the study.

The authors defined resolution of VOC as the first of the following to occur: sustained decrease in Visual Analog Scale (VAS) pain score of at least 1.5 cm from baseline and transition to oral analgesics; readiness for hospital discharge as determined by the patient and physician; or discharge to a home setting.

Patients receiving GMI-1070 achieved a mean resolution of VOC 41 hours earlier and a median resolution of VOC 63 hours earlier than the placebo group.

At 48 hours, 39.5% of patients in the GMI-1070 group and 24.2% of patients in the placebo group achieved a resolution of VOC. At 120 hours, 65.1% and 45.5% of patients, respectively, had a VOC resolution. Patients in the GMI-1070 group had a mean hospital length of stay of 132 hours compared with 182 hours for the placebo group.

Dr. Telen said VOC is the most common disease manifestation in sickle cell disease, accounting for more than 75,000 hospitalizations each year in the United States. In pre-clinical studies, researchers found that GMI-1070 reduced cell adhesion and abrogated VOC. In animal models, GMI-1070 increased survival, improved blood flow in the microvasculature, and reduced leukocyte/endothelial and leukocyte/red blood cell interactions. Phase 1 studies also demonstrated the drug’s safety in patients with and without sickle cell disease.

In this trial, 76 adult and pediatric patients received GMI-1070 or placebo in addition to the standard of care when they entered the hospital with VOC exacerbated by chronic pain. They had a mean age of approximately 25 years, and approximately 40% were males. Patients were excluded if they had a serious infection, acute chest syndrome, significant organ dysfunction, pain atypical of VOC, serum creatinine >1.2 mg/dL for adults or >1.0 mg/dL for children <16 years of age, a large number of hospitalizations for VOC, or a recent red blood cell transfusion.

The authors enrolled patients at 17 sites during a 31-month period from 2010 to 2012 and amended the protocol 4 times. They planned on including patients aged 16 to 45 years before adding patients aged 12 to 45 years and 45 to 60 years. They also doubled the dose of GMI-1070 as a result of the planned, interim pharmacokinetic analysis. Of the 76 patients, 45 received the higher dose regimen.

The authors found that approximately 45% of patients in each group first achieved a sustained reduction in VAS score of at least 1.5 cm and a transition to oral analgesics. For this end point, the GMI-1070 group had a significantly faster resolution of VOC, according to Dr. Telen. In addition, 42% of patients in the GMI-1070 group and 49% of patients in the placebo group first were deemed ready for hospital discharge. Patients receiving GMI-1070 were deemed ready for discharge by a mean of 35 hours and a median of 64 hours earlier than patients taking placebo. The time to discharge was reduced by a mean of 55 hours and a median of 84 hours in the GMI-1070 group compared with the placebo group.