Global Blood Therapeutics, Inc. announced The Lancet Haematology has published the complete analysis of 72-week data from the Phase 3 HOPE Study of Oxbryta® (voxelotor) tablets in patients with sickle cell disease (SCD). The results showed significant and sustained improvement in haemoglobin levels, reduction in hemolysis and improved overall health status in patients treated with Oxbryta. These findings support the long-term use of Oxbryta to reduce haemolytic anemia and haemolysis in SCD, potentially mitigating life-threatening complications of the condition.
Oxbryta, a first-in-class oral, once-daily therapy, directly inhibits haemoglobin polymerization, the root cause of the sickling and destruction of red blood cells in SCD. Oxbryta is approved in the United States for the treatment of SCD in patients ages 12 years and older, and is also pending full marketing authorisation by the European Medicines Agency (EMA) in Europe.
“Sickle cell disease is a devastating disease that can lead to organ damage and a shortened life expectancy and is complicated by significant disparities in access to quality care,” said Professor Jo Howard of Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London. “Fortunately, we have entered a new era of treatment. The HOPE Study is the longest registrational trial to date among recently approved therapies for sickle cell disease, and these results further demonstrate that by sustainably improving both the hemolysis and anemia manifestations of the disease, Oxbryta has the potential to be a safe and effective disease-modifying treatment in patients with sickle cell disease.”
The HOPE Study, a randomized, double-blind, placebo-controlled, international, multicenter trial in 274 patients ages 12 to 65 years with SCD, showed treatment with the U.S. FDA-approved dose of Oxbryta 1500 mg resulted in rapid and durable improvements in hemoglobin levels throughout 72 weeks of treatment. Approximately 90 percent of patients treated with Oxbryta achieved a haemoglobin improvement of >1 g/dL from baseline at one or more time points during the study compared to placebo (25 percent). In addition, approximately 59 percent of patients treated with Oxbryta 1500 mg were able to achieve a hemoglobin increase of >2 g/dL and 20 percent achieved >3 g/dL at one or more time points, compared to approximately 3 percent and no patients in the placebo group, respectively. The analysis also showed that study participants treated with Oxbryta had numerically fewer vaso-occlusive crises (VOCs), consistent with the trends at 24 weeks, and were three times less likely to experience an acute anaemic episode (decrease in hemoglobin >2 g/dL from baseline).
Additionally, approximately 74 percent of patients (39 of 53) taking Oxbryta had their overall clinical status rated as “moderately improved” or “very much improved” by their clinician compared with approximately 47 percent (24 of 51) of the placebo group, a statistically significant difference. Treatment with Oxbryta remained generally well tolerated, and rates of adverse events were similar between treatment groups over 72 weeks.
“The sickle cell disease community, which for decades has been dramatically underserved, deserves treatments that address the sickling and destruction of red blood cells due to hemoglobin polymerization – the root cause of this disease,” said Ted W. Love, M.D., President and Chief Executive Officer of GBT. “The HOPE Study represents a significant milestone in advancing the treatment of SCD, and we are building on this groundbreaking trial with our commitment to increase access to Oxbryta and develop novel therapeutics that can transform SCD into a well-managed disease.”
Findings from a post hoc analysis of the HOPE Study published recently in the American Journal of Hematology evaluated the incidence and outcomes of leg ulcers in SCD patients and further support the foundational role of haemoglobin S polymerization inhibition in SCD treatment.1 Results of the analysis showed leg ulcers improved or resolved by week 72 in all patients (5 of 5) receiving Oxbryta 1500 mg compared with 63 percent of patients (5 of 8) in the placebo group. Resolution of leg ulcers was associated with increases in hemoglobin levels and decreases in hemolysis. Patients who experienced a hemoglobin increase of >1.0 g/dL while treated with Oxbryta were most likely to experience resolution of their leg ulcers within 24 weeks. These results highlight the potential of Oxbryta to meaningfully impact major patient outcomes.
- Minniti CP, et al. The impact of voxelotor treatment on leg ulcers in patients with sickle cell disease. Am J Hematol. 2021. https://doi.org/10.1002/ajh.26101. Accessed March 2, 2021.