Benzinga | Dec 12, 2021 10:05AM EST

GBT Presented Positive New Data on Oxbryta (voxelotor) in Patients with Sickle Cell Disease at ASH 2021; Said Real-world Experience Study of More Than 3,100 Patients Demonstrates Statistically Significant Reductions in Transfusions, Vaso-occlusive Crises and Hospitalizations in Patients Treated With Oxbryta

lobal Blood Therapeutics, Inc. (GBT) (NASDAQ:GBT) today announced positive results from real-world and long-term studies with Oxbryta(r) (voxelotor) tablets for the treatment of sickle cell disease (SCD). A first-in-class oral, once-daily therapy, Oxbryta directly inhibits sickle hemoglobin polymerization, the root cause of the sickling and destruction of red blood cells in SCD. Results from a large retrospective analysis of 3,128 SCD patients treated with Oxbryta showed a statistically significant improvement in hemoglobin (Hb) levels, and statistically significant reductions in transfusions, vaso-occlusive crises (VOCs) and hospitalizations. These data, as well as Phase 1 results for inclacumab, GBT's investigational P-selectin inhibitor, were presented at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition, taking place from December 11-14, 2021 in Atlanta, Georgia and online.

"We're thrilled with the data presented at ASH, which demonstrate the clinically meaningful impact of Oxbryta for patients living with sickle cell disease. The benefits of Oxbryta were reinforced in this large retrospective study to evaluate the impact of an SCD medicine on clinical outcomes and healthcare resource utilization in a real-world setting," said Kim Smith-Whitley, M.D., executive vice president and head of research and development of GBT. "We continue our commitment to the sickle cell disease community in our pursuit of developing innovative treatments that address the urgent needs of patients."

Oxbryta Real-World Experience

A total of 3,128 SCD patients in the United States ages 12 and older were included in the retrospective analysis (Poster #2052) from the Symphony Health claims database. This study of medical and pharmacy claims for patients who initiated Oxbryta treatment between November 2019 and June 2021 compared annualized rates per patient-year (PPY) for transfusions, VOCs and VOC-related and all-cause hospitalizations for the three months before Oxbryta initiation versus the period after beginning the treatment. Among patients with at least one recent transfusion prior to initiating treatment, there was a 52% mean reduction in the number of transfusions after beginning Oxbryta. Patients with VOCs in the pre-study period experienced a mean reduction of 23% in the number of VOCs after initiating treatment. After starting Oxbryta, the mean number of VOC-related hospitalizations decreased by 34%, while the mean number of all-cause hospitalizations decreased by 37% among patients who were recently hospitalized. Approximately 61% of patients for whom Hb lab data were available showed increased Hb levels of greater than 1 g/dL during follow up consistent with the results from the Phase 3 HOPE Study.

"These data presented at ASH contribute to the growing body of evidence on the real-world clinical benefit of Oxbryta, providing additional support for its use in the treatment of sickle cell disease and management of associated complications," said Nirmish Shah, M.D., associate professor of medicine, pediatrics, Duke University School of Medicine. "It is encouraging that patients have an available innovative therapeutic option that has the potential to modify the course of this devastating disease."

Additional Oxbryta Studies at ASH 2021

An analysis of an ongoing open-label extension (OLE) of the Phase 3 HOPE Study (Poster #3114; will be presented on December 13) confirmed the safety and efficacy of long-term Oxbryta use in SCD patients ages 12 and older. The improvements in Hb and markers of hemolysis that were observed in the HOPE study were sustained in the OLE period for patients who previously received 900 mg and 1,500 mg of Oxbryta, demonstrating a durability of response. Patients who switched from placebo to Oxbryta saw improvements in Hb levels and measures of hemolysis from the start of the OLE through week 48, consistent with the HOPE Study results.

Data from the ongoing Retrospective Study to Evaluate Outcomes in Patients with Sickle Cell Disease Treated with Oxbryta (RETRO) (Poster #3100; will be presented on December 13), the first multicenter, retrospective study to examine the real-world effectiveness of Oxbryta, showed the treatment was associated with increased Hb levels and decreased hemolytic markers. Additional findings are expected to be presented in 2022 to enable a deeper understanding of the long-term efficacy and safety of Oxbryta.

Safety data across the HOPE OLE and RETRO studies of Oxbryta were consistent with those from the Phase 3 HOPE Study of SCD patients ages 12 years and older.

Inclacumab Phase 1 Dosing Analysis in Healthy Volunteers

An analysis (Poster #977) of a Phase 1 study of inclacumab, GBT's fully human P-selectin monoclonal antibody in development for the reduction of VOCs in SCD patients, showed a well-tolerated safety profile for up to 29 weeks following a single dose of 20 or 40 mg/kg in 15 healthy subjects. Plasma inclacumab exposures were dose-proportional over the dose range tested and demonstrated expected pharmacokinetics for healthy subjects, with apparent nonlinearity below approximately 10 g/mL, suggesting target-mediated drug disposition.

Target concentration for both doses at 12 weeks was greater than the target activity threshold of 10 g/mL, which was associated in prior studies of inclacumab with full inhibition of the formation of platelet-leukocyte aggregate (PLA), a known factor in the development of vascular lesions and cardiovascular events. The results support best-in-class potential for inclacumab at the dose of 30 mg/kg every 12 weeks in patients with SCD-related VOCs, which is the dose being studied in GBT's two ongoing Phase 3 THRIVE (THerapy for Reduction with Inclacumab of VOC Episodes) trials (NCT04935879 and NCT04927247).