The benefits of voxelotor in patients with sickle cell disease are durable, with no new safety signals, according to longer-term data from the HOPE-3 study. "Our results support the sustained and chronic use of voxelotor to reduce anemia and hemolysis, and show that the chronic use of this drug is as an important new treatment option that has the potential to address the substantial morbidity of hemolytic anaemia in sickle cell disease," researchers write in The Lancet Haematology. Voxelotor is a first-in-class oral, once-daily therapy that inhibits sickle hemoglobin polymerization, the root cause of sickle cell disease (SCD). It was approved in the United States in 2019 for adults and adolescent patients aged 12 and older at a dose of 1,500 mg once daily. The approval was based on 24-week results from the HOPE-3 study, which was funded by Global Blood Therapeutics, which makes voxelotor (Oxbryta). The trial enrolled 274 SCD patients, with random allocation to voxelotor (900 or 1500 mg once daily) or placebo for 72 weeks. At 24 weeks, treatment with voxelotor led to significant improvements in hemoglobin levels, accompanied by reductions in hemolysis, according to a June 2019 report in The New England Journal of Medicine. Half of the patients (51%) receiving voxelotor 1,500 mg/daily achieved an increase of greater than 1 g/dL in hemoglobin compared with 7% receiving placebo (P<0.001). The complete results now show that the improvements in hemoglobin concentrations and reductions in markers of hemolysis were maintained out to week 72. Of note, nearly 90% of patients taking voxelotor 1,500 mg/daily achieved a hemoglobin improvement of greater than 1 g/dL from baseline at one or more time points during the study compared to 25% of placebo patients. Fifty-nine percent of patients taking voxelotor 1,500 mg achieved a hemoglobin increase of greater than 2 g/dL and 20% achieved greater than 3 g/dL at one or more time points. Patients treated with voxelotor had numerically fewer vaso-occlusive crises, consistent with the trends at 24 weeks, and were three times less likely to experience an acute anemic episode. Three-quarters (74%) of patients taking 1,500 mg voxelotor had their overall clinical status rated as "moderately improved" or "very much improved" by their clinician compared with 47% of placebo patients. "No new safety signals were identified in this long-term investigation of voxelotor," the team reports. The most common side effects seen in patients taking voxelotor are headache, diarrhea, abdominal pain, nausea, fatigue, rash and fever. "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," lead author Dr. Jo Howard of Guy's and St. Thomas' NHS Foundation Trust, in London, said in news release from Global Blood Therapeutics announcing the final results. "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," said Dr. Howard. The HOPE-3 study was funded by Global Blood Therapeutics. Several authors have disclosed financial relationships with the company. —Reuters Staff Source
