Global Blood Therapeutics reported new data from its Phase III HOPE trial of voxelotor in sickle cell disease (SCD), showing the primary endpoint, improvement in hemoglobin greater than 1 g/dL at 24 weeks, was reached. The research was published in The New England Journal of Medicine and was presented on June 17, 2019 at the Presidential Symposium at the 24th European Hematology Association (EHA) Congress in Amsterdam.
The randomized, double-blind HOPE trial was a two-part study designed to evaluate the effectiveness and safety of voxelotor 1500 mg compared with placebo in sickle cell patients ages 12 to 65. The new results from the HOPE Study include 24-week efficacy data from 274 patients enrolled in the study from 60 institutions across 12 countries. In the study, voxelotor provided a rapid, statistically significant and sustained improvement in hemoglobin levels and reduced the incidence of worsening anemia and hemolysis. Hemoglobin improved rapidly from baseline to the earliest timepoint measured (2 weeks) with voxelotor 1500 mg and was sustained through 24 weeks. The improvement in hemoglobin was similar in patients with or without background use of hydroxyurea. Voxelotor 1500 mg increased hemoglobin levels to a mean of 9.8 g/dL at 24 weeks from a baseline of 8.6 g/dL, consistent with a clinically meaningful improvement in anemia. There were numerically fewer vaso-occlusive crises (VOCs) and a lower annualized incidence rate (per person-year) of VOCs with voxelotor versus placebo, despite the significant increases in hemoglobin with voxelotor treatment. Voxelotor was generally safe and well tolerated. There was no evidence of impairment of tissue oxygenation.
This data will form the basis of the rolling submission of a New Drug Application for voxelotor, which the company is on track to complete in the second half of this year for review under an accelerated approval pathway.
The FDA granted voxelotor Breakthrough Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations for the treatment of patients with SCD. The European Medicines Agency (EMA) has included voxelotor in its Priority Medicines (PRIME) program, and the European Commission (EC) has designated voxelotor as an orphan medicinal product for the treatment of patients with SCD.
About Sickle Cell Disease
SCD is a lifelong inherited blood disorder caused by a genetic mutation in the beta-chain of hemoglobin, which leads to the formation of abnormal hemoglobin known as sickle hemoglobin (HbS). In its deoxygenated state, HbS has a propensity to polymerize, or bind together, forming long, rigid rods within a red blood cell (RBC). The polymer rods deform RBCs to assume a sickled shape and to become inflexible, which causes hemolytic anemia (low hemoglobin due to RBC destruction) that can lead to multi-organ damage and early death. This sickling process also causes blockage in capillaries and small blood vessels. Beginning in childhood, SCD patients typically suffer unpredictable and recurrent episodes or crises of severe pain due to blocked blood flow to organs, which often lead to psychosocial and physical disabilities.
Voxelotor (previously called GBT440) is an oral, once-daily therapy. Voxelotor works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, Global Blood Therapeutics believes voxelotor blocks polymerization and the resultant sickling and destruction of red blood cells. With the potential to improve hemolytic anemia and oxygen delivery, the company believes that voxelotor may potentially modify the course of SCD.