Global Blood Therapeutics, Inc. announced the completion of a planned review of Part A of the Phase 3 HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) Study, which is evaluating voxelotor for the treatment of sickle cell disease (SCD). On the primary endpoint (the proportion of patients with greater than 1 g/dL increase in hemoglobin versus baseline), a statistically significant increase was demonstrated with voxelotor at both the 1500 mg and 900 mg doses after 12 weeks of treatment versus placebo.
“Given the well-established association between chronic hemolytic anemia and SCD-related morbidity and mortality, we believe the clinically meaningful increase in hemoglobin and improvement in hemolysis together with the safety profile demonstrated in Part A are highly encouraging,” said Ted W. Love, M.D., president and chief executive officer of GBT. “Based upon voxelotor’s robust impact on hemolytic anemia, we believe it meets the standard for accelerated approval, and we look forward to providing further updates on our regulatory discussions as soon as possible, but no later than year-end.”
HOPE Study Part A Data
Results from the Part A analysis in 154 patients showed the following:
Efficacy and Safety
- 58 percent of patients taking the 1500 mg dose (p<0.0001) and 38 percent of patients taking the 900 mg dose (p=0.0021) achieved a greater than 1 g/dL increase in hemoglobin at 12 weeks versus 9 percent of patients taking placebo. This compares favorably to the hemoglobin increase assumption agreed to with the U.S. Food and Drug Administration (FDA) in the HOPE Study protocol of a 35 percent response.
- Statistically significant and dose-dependent improvements in hemoglobin, reticulocytes and bilirubin occurred with both voxelotor doses, further demonstrating an improvement in hemolytic anemia.
- Improvements in these clinical measures of anemia and hemolysis were similar in patients with or without background use of hydroxyurea. Approximately 64 percent of patients enrolled in Part A are on background use of hydroxyurea.
- There were numerically fewer VOC episodes in both voxelotor groups than in the placebo group, which as anticipated did not reach statistical significance due to limited patient follow-up.
- The patient reported outcomes (PRO) data were difficult to interpret due to low baseline symptom scores and high inter-subject and intra-subject variability. Given this, GBT does not plan to utilize the PRO as a key secondary endpoint.
- Voxelotor was generally safe and well tolerated with similar safety profiles between the two doses. There was no evidence of tissue hypoxia at either dose.
The independent Data and Safety Monitoring Board (DSMB) completed its most recent clinical safety review in May 2018 and did not identify safety concerns with voxelotor at either dose level across all patients dosed in the ongoing SCD clinical program, including adult patients in the Phase 3 HOPE Study and adolescent patients in the HOPE-KIDS 1 (GBT440-007) Study. The DSMB supported the initiation of dosing in children as young as age four.
GBT plans to present results from Part A at a medical meeting later this year.
Based on the positive Part A results and ongoing regulatory discussions, GBT continues to dose Part A patients, plus approximately 100 additional patients across all three treatment arms, to gather more data. At this time, GBT does not plan additional enrollment until it completes discussions with the FDA.
“The pathophysiology and morbidity associated with SCD result from two distinct pathways: hemolytic anemia and vaso-occlusion. New therapies that address each pathway are important and desperately needed,” said Elliot Vichinsky, M.D., director, Comprehensive Center for Sickle Cell Disease, UCSF Benioff Children’s Hospital Oakland. “Increasing hemoglobin levels by reducing hemolysis in SCD patients is likely to decrease morbidity and mortality.”
(Source: Global Blood Therapeutics, Inc.)
Filed Under: Drug Discovery