Voxelotor Before FDA for Approval as Possible Disease-modifying Treatment for Sickle Cell

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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The U.S. Food and Drug Administration (FDA) is giving priority review, as requested, to Global Blood Therapeutics‘ application to approve voxelotor as a treatment for sickle cell disease (SCD).

Voxelotor, formerly known as GBT440, is as an oral and once daily potential sickle cell therapy. It works by increasing the affinity of sickled hemoglobin molecules for oxygen, which, when oxygenated, prevents them from sticking to each other and forming clumps. As such, the therapy helps to stops the sickling and destruction of red blood cells that marks this disease.

“The FDA’s acceptance of our NDA [New Drug Application] for voxelotor under Priority Review is a major milestone in the development of this investigational therapy and further illustrates the significance the Agency places on getting important and innovative treatments to individuals living with SCD as quickly as possible,” Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics (GBT), said in a press release. “We look forward to working with the FDA during this process, with the goal of potentially changing the treatment paradigm for SCD.”

An FDA decision is expected on or before Feb. 26, 2020.

The application is supported by findings from the company’s ongoing Phase 3 HOPE trial (NCT03036813), assessing the safety and efficacy of voxelotor in treating SCD patients ages 12 to 65 compared to a placebo.

Expected to conclude in October, the trial enrolled 274 patients at 60 institutions across 12 countries, who were randomly assigned to voxelotor at a daily dose of either 900 mg or 1500 mg, or to a non-active placebo, for at least 24 weeks.

Trial findings, recently published in The New England Journal of Medicine, show that:

  • At the highest dose, voxelotor reduced the levels of two established biomarkers of red blood cell damage: reticulocytes (by 19.9%) and bilirubin (by 29.1%).
  • Voxelotor at either dose raised hemoglobin levels in almost half of all treated patients (48.4%), compared to 9% in those given placebo.
  • Treatment had a positive effect on preventing a vaso-occlusive crisis over time compared to placebo.
  • The incidence of adverse events was similar in both treated and untreated groups, and most were found to be unrelated to voxelotor or placebo.
  • Voxelotor use was safe and well-tolerated by patients.

The FDA previously placed voxelotor on its Fast Track to speed its development, and further supported the medication by awarding awarded it Orphan Drug, Rare Pediatric Disease and Breakthrough Therapy designations. The European Medicines Agency (EMA) has also included voxelotor in its Priority Medicines (PRIME) program.

If approved, voxelotor may represent SCD’s first disease-modifying treatment, or one that directly tackles its root cause, BGT said in the release.