- Global Blood Therapeutics is gambling initial data from a late-stage study of its experimental sickle cell disease drug will be sufficient to garner an OK from the Food and Drug Administration, announcing Wednesday its intent to file for an accelerated approval.
- Results from Part A of the Phase 3 trial showed Global Blood's treatment, called voxelotor, led to increased hemoglobin levels in significantly more patients than did placebo — signaling a beneficial effect on hemolytic anemia caused by the disease's characteristic sickling of red blood cells.
- Other measures tested, however, showed less clear-cut results in favor of voxelotor. While new options are desperately needed by sickle cell patients, it's not clear whether the FDA will agree to a speedy review of Global Blood's drug. Perhaps reflecting this uncertainty, shares in the biotech fell by 6% Wednesday.
Global Blood set up its Phase 3 trial of voxelotor with two parts. Part A tested two doses, 1500 mg and 900 mg, against placebo for three months and sought to finalize secondary endpoints for Part B, which would randomize more patients over six months.
On the primary measure comparing hemoglobin increases, voxelotor posted convincing results in Part A. Nearly 60% of individuals given the higher dose of the drug achieved a greater than one gram per deciliter increase in hemoglobin, compared to only 9% of those on placebo. Notably, this also widely surpassed the assumed 35% response in the study protocol.
This data spurred Global Blood to speed up its plans, pausing enrollment into Part B while it discusses submitting voxelotor for accelerated approval.
"I've become more and more convinced that it would be inappropriate for us not to pursue accelerated approval," said company CEO Ted Love on a conference call with analysts Wednesday morning.
"I personally, as CEO, felt a moral obligation that we had to consider a strategy that would make this drug available to patients in the United States as quickly as possible."
Global Blood met with the FDA earlier this week and anticipates giving further regulatory updates no later than the end of this year.
Because the company hopes to secure inclusion of the data at an upcoming medical meeting, detailed data beyond the topline results were not disclosed.
Yet results on other measures tested in Part A could give the FDA pause.
Voxelotor did not show, for example, a statistically strong impact on reducing the vascular occlusive crises (VOC) many sickle cell patients experience. There were numerically fewer VOC episodes in both voxelotor groups than placebo, but limited patient follow-up prevented demonstration of a significant difference, Global Blood said.
Speaking on Wednesday's conference call, Elliot Vichinsky, director of the Comprehensive Center for Sickle Cell Disease at UCSF Benioff Children's Hospital, made the case that addressing hemolytic anemia would more fundamentally change the course of the disease than aiming only at VOC.
Further clouding Global Blood's results were inconclusive patient-recorded outcomes data, which the company no longer intends to use as a key secondary endpoint.
Currently, sickle cell patients have limited treatment options and often need chronic blood transfusions which can, in turn, lead to toxic build-up of iron. Hydroxyurea can boost fetal hemoglobin levels in some patients and is the only disease-modifying drug approved.
New drugs are advancing through clinical development, however, including several gene therapies that have spurred hope for a transformative treatment. In the nearer term, Novartis hopes to submit its drug crizanlizumab for the treatment of sickle cell-related pain crises later this year.