Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat genetically defined diseases, today reported data for the first time from the ongoing long-term extension period of the
Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat genetically defined diseases, today reported data for the first time from the ongoing long-term extension period of the Phase 2 open-label study of mitapivat, a first-in-class, investigational, oral, small molecule allosteric activator of wild-type and a variety of mutated pyruvate kinase (PK) enzymes, in adults with non-transfusion dependent α- or β-thalassemia. Data from the study were featured in an oral presentation at the American Society of Hematology (ASH) Annual Meeting and Exposition, hosted virtually and in person from Dec. 11-14, 2021, in Atlanta.
Consistent with previously reported data, durable improvements in hemoglobin concentration and markers of hemolysis and ineffective erythropoiesis, were observed for up to 72 weeks of treatment in both α- and β-thalassemia patients. Mitapivat was well tolerated, and the safety profile was consistent with previous studies.
"The data presented today continue to demonstrate that chronic treatment with mitapivat is well tolerated and has the potential to meaningfully improve hallmarks of thalassemia, including hemolysis and ineffective erythropoiesis. I am particularly excited by the data generated in α-thalassemia, as there are no currently approved therapies for this subtype," said Kevin Kuo, M.D., hematologist at University Health Network, University of Toronto, and an investigator in the study. "Mitapivat has the potential to be an important treatment option for people with this lifelong disease characterized by severe complications, and I look forward to its continued advancement in pivotal clinical trials."
Long-term Efficacy and Safety of the Oral Pyruvate Kinase Activator Mitapivat in Adults with Non-transfusion-dependent Alpha- or Beta-Thalassemia (Abstract #576)
The open-label Phase 2 study evaluated the efficacy, safety, pharmacokinetics and pharmacodynamics of mitapivat treatment in adults with either non-transfusion-dependent α- or β-thalassemia who have a baseline hemoglobin concentration of ≤10 g/dL. The trial enrolled 20 patients. All patients were treated with an initial dose of 50 mg mitapivat twice daily followed by a dose-level increase to 100 mg twice daily at the Week 6 visit based on safety evaluations and hemoglobin concentrations. Following the completion of the 24-week core period, patients had the opportunity to enroll in an optional 10-year extension period to evaluate long-term efficacy and safety of mitapivat in this population. As of the data cut-off date of March 27, 2021, 17 of the 20 patients remain in the extension phase with a median treatment duration of 70.9 weeks (range 54.7-105.6).
As of the data cut-off, efficacy results were as follows:
- Mean hemoglobin increase from baseline to Week 60 (α-thalassemia, n = 4; β-thalassemia, n = 9) was 1.5 g/dL.
- Mean hemoglobin increase from baseline to Week 72 (β-thalassemia, n = 8) was 1.7 g/dL.
- Improvements in markers of hemolysis and ineffective erythropoiesis achieved during the core period were sustained among both α- and β-thalassemia patients, up to Week 72.
Adverse events (AEs) for patients who continued in the study (n=17) were comparable in the core and extension periods. No new safety signals were identified in the extension period.
"Following encouraging results from our Phase 2 trial of mitapivat – the first clinical study of a PK activator in thalassemia and the first drug trial in α-thalassemia – we are now focused on advancing the development of mitapivat for patients as quickly and efficiently as possible," said Sarah Gheuens, M.D., Ph.D., chief medical officer at Agios. "Our two global, placebo-controlled pivotal trials of mitapivat – ENERGIZE and ENERGIZE-T – have been initiated, and we look forward to enrolling the first patients soon."
Mitapivat is not approved for use by any regulatory authority.