Forma Therapeutics Presents Clinical Proof-of-Concept Data at the 62nd Annual ASH Meeting Supporting the Potential of its Novel Investigational PKR Activator, FT-4202, to Treat Sickle Cell Disease (SCD)
6 of 7 (86%) patients on 300 mg of FT-4202 for 14 days achieved a hemoglobin increase > 1 g/dL from baseline
Hemolytic markers support the hypothesis that FT-4202 improves red blood cell survival and reduces turnover
A favorable tolerability profile was observed after once-daily dosing of FT-4202 for 14 days and a 7-day follow up period in patients with SCD
Initiated 600 mg MAD2 cohort and 12-week open label extension study
“These results are remarkable for a Phase 1 study, and they’re encouraging for sickle cell patients,” said
“We are pleased to present our clinical proof-of-concept data and continue to see potential for FT-4202 to improve the lives of people living with sickle cell disease,” said
FT-4202, an Allosteric Activator of Pyruvate Kinase-R, Demonstrates Proof of Mechanism and Proof of Concept after a Single Dose and after Multiple Daily Doses in a Phase 1 Study of Patients with Sickle Cell Disease
The data will be presented in an oral presentation by
The results announced today are based on nine patients with SCD (FT-4202 n=7; placebo n=2) randomly assigned to receive a single oral dose of 300 mg daily of FT-4202 or placebo for 14 days. The data show that, from baseline, in patients receiving FT-4202:
- 6 of 7 achieved a > 1 g/dL increase in hemoglobin (Hb); median 1.2 g/dL increase (range 0, 2.3 g/dL);
- 2,3-DPG levels were reduced, thus increasing oxygen affinity and decreasing sickle hemoglobin polymerization;
- Adenosine triphosphate (ATP) levels were increased resulting in improved RBC function and reduced hemolysis;
- 7 of 7 achieved a reduction in reticulocytes; median 60% decrease (range -39%, -81%);
- 6 of 7 achieved a reduction in lactate dehydrogenase (LDH); median 36% decrease (range +18%, -57%); and
- 7 of 7 achieved a reduction in bilirubin; median 35% decrease (range -7%, -63%).
The tolerability data presented today are based on nine patients enrolled at the time of submission of the presentation to ASH. Since then, findings from these nine patients have been unblinded. Among the seven patients receiving FT-4202, the tolerability analysis indicates:
- Eighteen adverse events (AEs) were reported;
- Two Grade 1 AEs considered possibly related to study treatment were reported by one patient each and included headache and nausea;
- No treatment-related serious AEs were reported.
Non-treatment-related AEs were consistent with sickle cell disease-related events commonly experienced in this patient population.
The ongoing Phase 1 study is evaluating the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single ascending dose and multiple ascending doses of FT-4202, first in healthy volunteers and now in patients with sickle cell disease. Based on the safety results and tolerability profile observed in the initial multiple dose cohort of patients, a second multiple dose cohort is being enrolled in which patients are randomly assigned to receive a single daily 600 mg oral dose of FT-4202 or placebo for 14 days. Patients who complete this second 14-day dose cohort can then enroll into a 12-week, open label cohort receiving a single daily 400 mg oral dose of FT-4202. For more information, please visit clinicaltrials.gov/NCT03815695.
The data presented today, along with the results from the single 700 mg dose arm of the study presented in
About Sickle Cell Disease
Sickle cell disease (SCD) is one of the most common single-gene disorders and is estimated to affect approximately 100,000 people in
FT-4202 is a novel investigational selective red blood cell (RBC) pyruvate kinase-R (PKR) activator designed to be a disease-modifying therapy for the treatment of sickle cell disease (SCD). Employing a multimodal approach, FT-4202 is designed to work upstream by activating the RBCs’ natural PKR activity to decrease 2,3-DPG levels, 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 RBC health and survival. Together, these effects are anticipated to increase hemoglobin levels and decrease painful vaso-occlusive crises. In preclinical safety studies, FT-4202 did not inhibit aromatase activity or affect steroidogenesis, important biological processes responsible for sexual development. FT-4202 has been granted Fast Track, Rare Pediatric Disease and Orphan Drug designations from the
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