Sickle Cell Disease

February 16, 2015

Emmaus Life Sciences released results of a phase III study of oral pharmaceutical grade L-glutamine (PGLG) treatment for sickle cell anemia and sickle beta-0 thalassemia. The multi-center, double-blind clinical trial studied PGLG for sickle cell disease (SCD) in 230 pediatric patients as young as five years old and adults. Study participants were randomized to receive daily PGLG (152 patients) or placebo (78 patients) for 48 weeks, after which treatment levels were tapered to zero. Researchers observed patients who received PGLG experienced fewer painful crises (three v. four events during the study period, a 25% reduction) and a longer time to a pain crisis than patients receiving placebo. Treated patients also were less likely to be hospitalized (two v. three events during the study period, a 33% reduction) and spent less time in the hospital for these events (6.5 v. 11 days, a 41% reduction) than those receiving placebo. The percentage of patients experiencing acute chest syndrome, a severe complication of SCD, was less than half among the PGLG group as compared to the placebo group (11.9% v. 26.9%, or 58% fewer cases). The therapy has Orphan Drug designation in the U.S. and Europe and Fast Track designation from the FDA.

December 3, 2012

AesRx released results from a phase I trial of Aes-103 for the treatment of sickle cell disease. This first-in-human, double-blind, placebo-controlled study enrolled 20 healthy volunteers of African-American descent. Subjects received single doses of Aes-103 at 300mg, 1000mg, 2000mg and 4000mg, or placebo. The pharmacokinetics of Aes-103 showed five-fold to 10-fold higher drug concentrations in red blood cells, which is the site of action of Aes-103 on hemoglobin, compared to drug concentrations in plasma. Aes-103 was rapidly absorbed and the amount of Aes-103 in plasma and red blood cells was largely dose proportional. In a hypoxia challenge test, subjects inhaled low levels of oxygen (12%) while their blood oxygen levels (SpO2%) were monitored. Aes-103 in 1000-4000mg doses reduced the hypoxia-related drop in subjects’ SpO2% compared to placebo and the 300mg dose. The drug’s ability to provide protection in a hypoxia challenge of healthy volunteers indicated biological activity in humans in a manner consistent with Aes-103’s proposed mechanism of action in sickle cell disease. Aes-103 was well tolerated. All adverse events were mild and transient. Based on these results, AesRx initiated a phase II trial of similar design enrolling patients with sickle cell disease.

October 20, 2008

BioMarin released positive results from a phase IIa trial of 6R-BH4 for the treatment of sickle cell disease. This multi-center, open-label study enrolled 32 subjects with sickle cell disease not receiving hydroxyurea therapy, in the US. The subjects received 6R-BH4 orally at 2.5 mg/kg, 5 mg/kg, 10 mg/kg and 20 mg/kg for four weeks each in this 16-week dose-escalation study. Data are from 21 subjects who completed the trial. Endothelial dysfunction showed improvement over baseline levels at week eight (5 mg/kg; p=0.042), week 12 (10mg/kg; p=0.003) and week 16 (20 mg/kg; p=0.075). The subjects with abnormal peripheral arterial tonometry (PAT) scores of less than or equal to 1.67 at baseline demonstrated greater improvement at all dose levels (2.5, 5, 10 and 20 mg/kg). The mean endothelial function PAT score improved from the abnormal to the normal range (>1.67) in subjects an abnormal PAT score at baseline. Treatment was well tolerated. Based on the results, BioMarin plans to move forward with the development of 6R-BH4 for the treatment of sickle cell disease.

April 9, 2007

Icagen released negative results from a phase III trial of senicapoc for the treatment of sickle cell disease. This randomized, double-blind, placebo-controlled trial enrolled 300 subjects who were to receive senicapoc or placebo for up to 1 year. The primary endpoint was rate of vaso-occlusive crisis. Secondary endpoints included change in hemoglobin levels. Treatment was safe and well tolerated, with no differences between the senicapoc and placebo groups. Expected increases in hemoglobin and hematocrit and decreases in reticulocytes as well as lactate dehydrogenase and bilirubin, markers of hemolysis, were observed. However, the study looked unlikely to meet the primary endpoint. Based on the results, Icagen terminated the trial. The company plans to further analyze the data in order to determine a future course of action for senicapoc.

August 25, 2003

SuperGen reported positive results from a phase I/II study investigating Dacogen (decitabine), an anticancer agent for the treatment of sickle cell anemia. Data showed that all subjects treated with Dacogen had increased levels of fetal hemoglobin and levels of total hemoglobin increased an average of 26%. Results also showed that clinical indicators of sickle cell disease also improved among Dacogen treated subjects. The treatment was well tolerated, with the only significant toxicity being neutropenia. The study enrolled eight subjects with sickle cell anemia who were resistant or intolerant to hydroxyurea. Subjects received Dacogen administered subcutaneously, one-to-three times per week, in two cycles of six-week duration. Results were published in the August issue of the journal Blood.