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FORMA Therapeutics announces FT-4202 granted fast track designation and rare paediatric disease designation to treat sickle cell disease

The US FDA’s Centre for Drug Evaluation and Research (Credit: The U.S. Food and Drug Administration)

“These designations for FORMA’s lead clinical asset underscore the FDA’s continued recognition of the needs of patients with SCD,” said Frank Lee, chief executive officer of FORMA Therapeutics. “With more than 100,000 individuals living with SCD in the U.S., and with relatively few treatment options, we believe significant unmet medical needs persist. These FDA designations give FORMA the opportunity to accelerate the development of a new treatment for people impacted by SCD.”

FORMA is currently enrolling patients with SCD in a Phase 1 study to evaluate the safety and pharmacokinetics/pharmacodynamics (PK/PD) of FT-4202. FORMA plans to initiate a registrational trial within the next year. For more information on eligibility and study sites for the open Phase 1 study.

The FDA’s Fast Track designation is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Fast Track designation allows for early and frequent communication with the FDA throughout the entire drug development and review process. It also enables eligibility for Accelerated Approval and Priority Review, as well as a rolling review of a company’s New Drug Application, if relevant criteria are met.1

Under the FDA’s Rare Pediatric Disease (RPD) program, a sponsor who receives marketing approval for a product with an RPD designation may be eligible for a voucher that can be redeemed to obtain priority review for any subsequent marketing application. The FDA defines a “rare pediatric disease” as a rare disease in which the serious or life-threatening manifestations primarily affect individuals from age zero to 18.2

Sickle cell disease (SCD) is the most common disorder caused by a single gene mutation. Worldwide, an estimated 300,000 children are born with SCD each year. In the U.S., prevalence of SCD is approximately 100,000 people. In people living with SCD, red blood cells, or RBCs, spontaneously deform in low oxygen conditions, taking on a sickle-like shape. Sickled cells are stiff and have damaged membranes, causing the RBCs to clump and burst in small blood vessels, resulting in inflammation and vaso-occlusive crises. Repeated deformation also depletes the RBC energy supply, called ATP. One important consequence of this energy depletion is increased levels of a metabolite, 2,3-DPG, that further reduces the RBCs’ affinity for oxygen and exacerbates the cycle of repeated deformation and anemia.

FT-4202 is a novel 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 works 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 increases 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.

Source: Company Press Release