Newly published results from a multinational study co-authored by Kenneth Ataga, MD, director of the Center for Sickle Cell Disease at the University of Tennessee Health Science Center (UTHSC) and the Memphis Consortium for Sickle Cell Disease and Non-Malignant Hematology Research, indicated voxelotor, a novel experimental drug for sickle cell disease, reduced anemia and boosted the health of red blood cells in patients. Dr. Ataga is also the Methodist Endowed Chair in Sickle Cell Anemia at Methodist Le Bonheur Healthcare.
Sickle cell disease is an inherited blood disorder that affects red blood cells. It is caused by a genetic mutation in hemoglobin, resulting in the formation of abnormal hemoglobin known as sickle hemoglobin (HbS). Deoxygenation and the sickling of red blood cells can lead to chronic anemia and hemolysis, and ultimately result in multiorgan damage, stroke, and premature death. More than 100,000 Americans are affected by sickle cell disease, and Memphis has one of the largest populations for adult sickle cell disease in the country. There are only two U.S. Food and Drug Administration-approved treatment options currently available.
“With the limited drug therapies available for patients with sickle cell disease, the findings of this trial are quite exciting,” said Dr. Ataga, who also serves as the Plough Foundation Endowed Chair in Sickle Cell Disease. “With the complex nature of sickle cell disease, the development of drugs that have different mechanisms of action offers an opportunity for combination drug therapy and for individualized therapy based on the presence of specific disease-related complications.”
The Biopharmaceutical company Global Blood Therapeutics, Inc. aims to bring voxelotor to the market as a third treatment option.
Designed to evaluate the efficacy and safety of voxelotor, the phase 3 Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization (HOPE) Study enrolled 274 patients, ages 12 to 65, with sickle cell disease, from 60 institutions across 12 countries. The patients were divided into three trial groups that received either a 900-mg or 1,500-mg daily dose of voxelotor or a placebo. Clinical assessments were performed at various time points throughout the trial.
The study found that 51 percent of the participants who were administered the higher dose of voxelotor experienced a significant increase in hemoglobin levels after six months of treatment compared to seven percent in the placebo group. In addition, voxelotor treatment reduced the incidence of worsening anemia and the amount of hemolysis. Voxelotor was also deemed safe and well-tolerated by participants.
“While voxelotor improved anemia in the study patients, more studies are required to show whether there are also improvements in other sickle cell disease-related complications,” Dr. Ataga said.
Longer-term follow-up studies are being planned to assess voxelotor’s effects on vaso-occlusive crisis (or sickle cell crisis), morbidity, and mortality in sickle cell patients.
The HOPE Study results were recently published in The New England Journal of Medicine and presented at the European Hematology Association 24th Congress in Amsterdam.