Forma Therapeutics has presented blinded data on sickle cell disease patients who received 600 mg of FT-4202. The high-dose cohort featured fewer hemoglobin responders than the 300-mg arm, but the safety profile offers encouragement for the ongoing phase 2/3 registrational trial.
Late last year, Forma established itself as a viable rival to Agios Pharmaceuticals and Global Blood Therapeutics in the sickle cell space by presenting data on recipients of the 300-mg dose of FT-4202. Like Agios’ mitapivat, FT-4202 is a pyruvate kinase R activator. Six of the seven patients who received the 300-mg dose of FT-4202 had hemoglobin increases of 1.0 g/dl or greater from baseline.
The response rate compared favorably to results from Agios and Global Blood, although the small size of the 300-mg cohort left room to question whether the data provided a true reflection of the efficacy of FT-4202. Now, Forma has followed up with data on seven patients who took the 600-mg dose.
Four of the seven patients had hemoglobin increases of 1.0 g/dl or greater from baseline. The higher dose fared numerically worse on other endpoints, too, lowering LDH in four patients, as opposed to the six people positively affected by the lower dose. The median change in LDH and reticulocytes, respectively hematologic and hemolytic biomarkers, was also numerically lower at 600 mg.
Yet, the hemoglobin response rate across the combined, 14-patient data set still holds up against the results generated by other companies, and Forma sees opportunities to improve outcomes. All the subjects in the phase 1 trial received FT-4202 once a day for 14 days. Based on the trajectory at the end of the treatment period, Forma said dosing patients beyond 14 days could bring benefits.
Forma will test that hypothesis in an open-label extension, which is dosing patients for 12 weeks. The open-label extension is giving a 400-mg dose. Forma is also using a 400-mg dose, as well as a 200-mg dose, in its phase 2/3 clinical trial. The primary endpoints of the phase 2/3 are hemoglobin response at Week 24 and vaso-occlusive crisis rate across the 52-week blinded treatment period.
The 600-mg cohort offers encouragement that the doses used in the registrational study will be safe and well tolerated, with investigators seeing no dose-limiting toxicities or treatment-related adverse events and adds to evidence that FT-4202 quickly increases hemoglobin in most patients.
To succeed in sickle cell disease, Forma will need to validate those findings in phase 2/3 and ideally show FT-4202 reduces the vaso-occlusive crisis rate. The painful crises occur when sickled cells block blood vessels. Novartis’ Adakveo reduces the crises. Global Blood’s Oxbryta increases hemoglobin. If FT-4202 can improve both measures, Forma may be able to win market share on two fronts.