RARE Daily

Forma Reports Positive Data in SCD Trial

March 31, 2021

Rare Daily Staff

Forma Therapeutics reported that new data from its ongoing randomized, placebo-controlled, multi-center phase 1 trial of FT-4202 in patients with sickle cell disease further support the development of the experimental therapy as a potential disease-modifying therapy.

Data previously presented at the 2020 American Society of Hematology Annual Meeting were based on the first cohort of patients in the phase 1 trial dosed with 300 mg of FT-4202 or placebo once daily for 14 days and a 7-day follow up period. The new findings include an analysis of the blinded data from the second cohort of patients randomly assigned to receive 600 mg of FT-4202 or placebo once daily for 14 days and a 7-day follow up period.

Sickle cell disease (SCD) is an inherited blood disorder caused by a mutation in the beta-globin gene that leads to polymerization of the sickle hemoglobin protein. In sickle cell disease, the red blood cells are misshapen in a sickle shape instead of the disc shape. The abnormal shape causes the cells to block blood flow causing anemia, pain crises, organ failure, and early death. There are an estimated 100,000 people in the United States currently living with sickle cell disease and more than an estimated 20 million individuals globally.

FT-4202 is a novel investigational selective red blood cell pyruvate kinase-R (PKR) activator designed to be a disease-modifying therapy for the treatment of SCD. FT-4202 is designed to work upstream by activating the red blood cell’s natural PKR activity, which leads hemoglobin to hold on to oxygen molecules longer to reduce RBC sickling. The downstream activity of FT-4202 is designed to increase ATP levels, the fuel that provides energy to cells, to improve red blood cell health and survival. Together, these effects are anticipated to increase hemoglobin levels and decrease painful vaso-occlusive crises. The FDA has granted FT-4202 Fast Track, Rare Pediatric Disease, and Orphan Drug designations, and FT-4202 has Orphan Drug designation from the European Commission.

Aggregate findings from the placebo-controlled cohorts of the phase 1 trial demonstrated 10 of 14 patients who received FT-4202 achieved a hemoglobin increase of greater than or equal to 1 g/dL from baseline with once-daily dosing of FT-4202 during 14 days of treatment. Based on a trend toward increasing response over the treatment period, the potential exists for additional benefit when dosing beyond 14 days, the company said. This is being explored in the ongoing open label extension, which is dosing patients at 400 mg daily for 12 weeks.

The data also showed activation of PKR by FT-4202 increased sickle RBC survival and reduced intravascular hemolysis in patients with SCD based on a reduction in reticulocytes, bilirubin, and LDH levels.

While the data from the 600 mg cohort of patients remain blinded, initial analysis of the cohort suggests FT-4202 has a similar safety and tolerability profile as the 300 mg cohort, despite the doubling of the dose. No dose-limiting toxicities or treatment-related adverse events were reported, and the overall adverse events profile of the 600 mg cohort was consistent with the 300 mg cohort.

“These results after only 14 days of treatment support the potential of FT-4202 to treat the underlying pathophysiology of the disease by increasing hemoglobin and reducing hemolysis, which may reduce the number and severity of vaso-occlusive crises SCD patients may experience annually,” said Patrick Kelly, chief medical officer of Forma.

Forma is currently enrolling adults and adolescents with SCD into the Hibiscus Study, a registrational phase 2/3 randomized, placebo-controlled, double-blind, multicenter trial to further evaluate the safety and efficacy of FT-4202 in this patient population.

Photo: Patrick Kelly, chief medical officer of Forma


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