GBT Launches Phase 2/3 Study for Next-gen Version of Oxbryta

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Global Blood Therapeutics (GBT) has begun a Phase 2/3 trial to study the safety, tolerability, effectiveness, and pharmacological properties of its experimental oral therapy GBT601 in people with sickle cell disease (SCD).

Initial data from the study (NCT05431088) are expected before the end of the year, according to GBT.

“The initiation of our Phase 2/3 trial is an important milestone in our efforts to bring GBT601 to patients,” Kim Smith-Whitley, MD, executive vice president and head of research and development at GBT, said in a press release.

The initial Phase 2 portion of the trial, which is not yet recruiting patients, seeks to enroll 60 adults with SCD, ages 18–65. To be eligible, prospective participants must have hemoglobin levels between 5.5 and 10.5 g/dL, and have experienced no more than 10 vaso-occlusive crises (VOCs) in the previous year. The study is expected to be conducted at sites in Africa, Europe, the Middle East, South America, and the U.S.

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Trial participants will initially be randomized to take GBT601 at doses of 100 or 150 mg a day. After safety data is available for the first six participants on 150 mg/day, a third dose group of 200 mg/day is planned.

The goal of the Phase 2 part of the study is to determine how GBT601 affects hemoglobin levels after 12 weeks of treatment. The experimental therapy’s pharmacological properties and relationship with markers of anemia and hemolysis (red blood cell death) will also be assessed.

Results from the Phase 2 part of the study will inform the dose used in the Phase 3 portion, which seeks to test GBT601 against a placebo in children and adults with SCD for 48 weeks. A third, open-label arm of the trial to assess the therapy’s safety and pharmacological properties in children with SCD is also planned.

“We anticipate that initial data from this trial as well as data from the continuation of our GBT601 Phase 1 study will be available before the end of the year,” Smith-Whitley said.

Hemoglobin is the protein in red blood cells responsible for carrying oxygen through the blood. SCD is caused by mutations that lead to the production of an abnormal version of this protein that tends to form clumps in red blood cells, causing them to take on the characteristic sickle-like shape that gives the disease its name.

GBT601 is designed to increase hemoglobin’s ability to bind oxygen, reducing its tendency to aggregate inside red blood cells. The experimental treatment is based on the same mechanism of action as GBT’s approved SCD therapy Oxbryta (voxelotor), but it is expected to have a more potent effect at lower doses.

“Based on compelling preclinical and clinical data, we believe GBT601 has the potential to be a best-in-class therapy for patients with sickle cell disease. Specifically, it has the potential to improve on the clinical results achieved with Oxbryta at a lower daily dose,” Smith-Whitley said.

GBT601 was generally well tolerated in Phase 1 studies, and early efficacy data suggested it boosted hemoglobin levels, while lowering those of hemolysis markers.

It was recently granted both orphan drug and rare pediatric disease designations by the U.S. Food and Drug Administration. These designations are given to experimental therapies to speed their development and regulatory review.