Agios Pharmaceuticals (Nasdaq: AGIO) has announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to tebapivat (AG-946), a novel pyruvate kinase (PK) activator, for the treatment of myelodysplastic syndromes (MDS). This designation underscores the potential of tebapivat to address a critical unmet need in patients with MDS, particularly those with lower-risk disease experiencing anemia. The orphan drug designation aims to support the development of medicines for rare disorders affecting fewer than 200,000 people in the U.S., offering incentives such as tax credits and potential market exclusivity.
Clinical Significance
Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios, emphasized the importance of this designation, stating, "Receiving orphan drug designation for tebapivat in MDS underscores the importance of bringing new oral treatment options to patients suffering from this rare disease. We aim to deliver the first oral therapy that addresses anemia due to ineffective erythropoiesis in lower-risk MDS, which affects approximately 75,000-80,000 patients in the U.S. and EU5 and accounts for approximately 70% of MDS cases."
Current Development Stage
Tebapivat is currently under evaluation as a potential oral therapy for anemia associated with lower-risk MDS. Agios has completed a Phase 2a study of tebapivat in lower-risk MDS and is initiating a Phase 2b study. The Phase 2b study is an open-label study in patients with anemia due to lower-risk MDS, with an estimated 80 patients enrolled across multiple locations.
Orphan Drug Designation Benefits
The FDA's Office of Orphan Drug Products grants orphan drug designation to support the development of medicines for rare disorders. Under the Orphan Drug Act, this designation qualifies Agios for incentives, including tax credits, exemptions from certain FDA fees for clinical trials, and the potential for seven years of market exclusivity following drug approval. These incentives are designed to encourage the development of treatments for rare diseases that might otherwise be overlooked due to limited commercial potential.
Mechanism of Action and Prior Designations
Tebapivat is a novel pyruvate kinase (PK) activator. Mitapivat, Agios’s lead PK activator, was previously granted FDA orphan drug designation for the treatment of PK deficiency, thalassemia, and sickle cell disease, highlighting the company's expertise in developing therapies for rare hematologic disorders.
Study Design of Phase 2b
The primary endpoint in the phase 2b study is transfusion independence for at least 8 consecutive weeks. Secondary end points include duration of transfusion independence and pharmacokinetics. Tebapivat is being administered at 3 dose levels for up to 24 weeks, and patients who complete the core period will be eligible to receive the same dose in the extension period for up to 156 weeks.
Patients were eligible for enrollment if they were at least 18 years old with documented diagnosis of MDS according to WHO classification, had received up to 2 prior therapies including erythropoiesis-stimulating agents (ESAs) and/or luspatercept, and had an ECOG performance status of 0 to 2.
