The hallmark of sickle cell disease is damage to a red blood cell protein called hemoglobin that carries oxygen to organs and tissue. The damage causes the cells to become shaped like sickles rather than having a normal disc shape. The sickling interferes with hemoglobin’s ability to deliver oxygen to tissue.
Global Blood designed voxelotor to increase sickle-shaped hemoglobin’s ability to carry oxygen.
The primary objective of the 24-week, Phase 3 HOPE trial (NCT03036813) is to see whether voxelotor does increase sickled hemoglobin’s ability to transport oxygen. Patients have been divided into two groups. One is receiving 900 mg of the therapy, and the other 1,500 mg.
One of the trial’s secondary objectives is to see if voxelotor can reduce the number of patients’ flare-ups. Common symptoms of the disease include weakness and pain in the hands or feet, belly, back, or chest.
One yardstick researchers will use to measure the therapy’s effectiveness is changes in patients’ scores in the Sickle Cell Disease Severity Measure index between the start and end of the trial. Another barometer will be changes in the same index’s Total Symptom Score.
The review board found no serious adverse events generated by voxelotor in either of the treatment groups. In addition, no patients had to drop out of the trial due to treatment reactions. The board found no safety concerns with voxelotor at either dose level.
Besides recommending that the study continue as planned, the board approved Global Blood Therapeutics’ request to add adolescents aged 12 to 17. The U.S. Food and Drug Administration had specified that the board needed to approve enrolling adolescents before they could be added.
The first review of the trial, “which opens up enrollment to younger patients, is an important milestone for the HOPE study,” Dr. Ted W. Love, president and chief executive officer of Global Blood Therapeutics, said in a press release. “We are encouraged that this independent committee has determined that voxelotor continues to be well tolerated.”
Love added that “the opportunity to include adolescent SCD [sickle cell disease] patients in the HOPE Study is a great step forward as we believe voxelotor has the potential to be a disease-modifying therapy that is needed in all age groups who suffer from this devastating disease.”
Recognizing that voxelotor may meet a critical need for new sickle disease treatments, both the FDA and the European Medicines Agency have taken steps to accelerate its development and regulatory approval. The FDA has given it fast track, orphan drug and rare pediatric disease designations. European regulators have included it in their priority medicines, or PRIME, program.
Global Blood is also conducting an ongoing Phase 2a trial of voxelotor’s ability to treat sickle cell disease patients from 6 to 17 years old. The HOPE-KIDS 1 study is assessing its safety, therapy properties, preliminary effectiveness, and patients’ ability to tolerate it.
“We remain on track to announce top-line data for our HOPE study in the first half of 2019, and we look forward to providing an interim update on our ongoing HOPE-KIDS 1 study” at the American Society of Hematology Annual Meeting in Atlanta, Dec. 9-12, Love said.