Mitapivat PDUFA for Thalassemia Delayed to December

The United States Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) goal date for Agios’ supplemental New Drug Application (sNDA) of mitapivat for the treatment of adult patients with non-transfusion-dependent (NTD) and transfusion-dependent (TD) alpha- or beta-thalassemia by 3 months to December 7, 2025.1

“We remain confident in the favorable benefit-risk profile of PYRUKYND in thalassemia,” Brian Goff, Chief Executive Officer, Agios, said in a statement.1 “We look forward to continuing our collaborative engagement with the FDA, with the goal of bringing this disease-modifying oral medicine to adult patients with thalassemia in the U.S.”

Mitapivat is an oral pyruvate kinase (PK) activator currently approved for treating adults with PK deficiency under the name Pyrukynd.2 Data supporting the sNDA submission are from the global, randomized, double-blind, placebo-controlled ENERGIZE and ENERGIZE-T Phase 3, which investigated mitapivat in people with NTD and TDT, respectively.

Agios reported in June 2024 that ENERGIZE met its primary endpoint, with oral mitapivat achieving a statistically significant increase in hemoglobin response rate compared with placebo in 122 (93.8%) patients in the mitapivat arm and 62 (96.9%) in the placebo arm who completed 24 weeks of follow-up.2

The study met its primary endpoint of hemoglobin response – an increase of ≥1 g/dL in average hemoglobin concentrations from Week 12 through Week 24 compared with baseline. Approximately 42% (n = 55) of patients in the mitapivat arm achieved a hemoglobin response, compared with 1.6% (n = 1) patients in the placebo arm (2-side P <.0001).2

Among those who achieved a response, the mean change from baseline in average hemoglobin concentration from Week 12 to 24 was 1.56 g/dL in the mitapivat arm. Hemoglobin response rates were higher among those treated with mitapivat versus placebo across all prespecified subgroups, including by thalassemia genotype (alpha - or beta-thalassemia) and baseline hemoglobin concentration (≤9.0 g/dL or 9.1 – 10.0 g/dL).

Mitapivat treatment also demonstrated statistically significant improvements for both key secondary endpoints, compared with placebo. The average change from baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale score from Week 12 to 24 was 4.85 (95% CI, 3.41 - 6.30) in the mitapivat arm, compared with 1.46 (95% CI, –0.43 to 3.34) in the placebo arm (P = .0026).2

Meanwhile, the average change from baseline in the average hemoglobin concentration from Week 12 to 24 was 0.86 (95% CI, 0.73 - 0.99) g/dL in the mitapivat arm, compared with –0.11 (95% CI, –0.28 to 0.07) g/dL in the placebo arm (P <.0001).2

Improvements were also identified in patients treated with mitapivat across various measures of health-related quality of life, including the 6-minute walk test, Patient Global Impression of Change (PGIC) fatigue, walking capacity, and thalassemia symptom subscales.

Safety results revealed a similar incidence of adverse events between the mitapivat and placebo arms during the 24-week double-blind period. Approximately 83% (n = 107) of patients in the mitapivat arm and 79% (n = 50) of patients in the placebo arm experienced treatment-emergent adverse events (TEAEs).2

Investigator Ali Taher, MD, PhD, professor of medicine, hematology & oncology and director of the Naef K. Basile Cancer Institute, American University of Beirut Medical Center, emphasized the importance of the results, stating that “based on the data collected in the ENERGIZE study, mitapivat has the potential to become a foundational treatment for non-NTD.”

References

1. Agios Provides Update on U.S. PDUFA Goal Date for PYRUKYND® (mitapivat) in Thalassemia. News release. Agios. September 4, 2025. https://finance.yahoo.com/news/agios-provides-u-pdufa-goal-110000331.html?guccounter=1&guce_referrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmNvbS8&guce_referrer_sig=AQAAAFFl8bRntQ7jzDSpQT2yEMwphCwzqvrvZs241SXjVkD_ec9ZU_lCcuz_YDwbH85DGqLdJQBRTBgZCRaVDXVuOK-e5ujLsGyvF2AfIK4wk6SG9WiJ4q2x8B5jCAb5kkzdCfux7HQ1QnYz3-WRthhflUqBD1575ABdC2Qmzxetg15i

2. FDA approves treatment for anemia in adults with rare inherited disorder. FDA. News release. February 17, 2022. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-anemia-adults-rare-inherited-disorder

3. Agios presents positive results from phase 3 energize study of mitapivat in non-transfusion-dependent thalassemia in plenary session at the European Hematology Association 2024 hybrid Congress. Agios Pharmaceuticals, Inc. June 15, 2024. Accessed June 17, 2024. https://investor.agios.com/news-releases/news-release-details/agios-presents-positive-results-phase-3-energize-study-mitapivat