Oral Mitapivat shows Promise for Non-Transfusion-Dependent Thalassemia in phase 3 trial

Statistical significance was also achieved for both key secondary endpoints associated with change from baseline in FACIT-Fatigue Score and hemoglobin concentration.

“The results of the Phase 3 ENERGIZE study underscore the potential of mitapivat to be a meaningful treatment option for adults with non-transfusion dependent alpha- or beta-thalassemia. All subgroup analyses favored the mitapivat treatment arm compared to placebo,” said Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios. “We are grateful to all of the patients who participated in this trial, our collaborators, study investigators and advisors in the patient and clinical communities for their partnership in achieving this milestone. These data bring us one step closer to a treatment for all thalassemia patients, and we look forward to the ENERGIZE-T readout mid-year.”

“The results of the ENERGIZE study support the potential of mitapivat to be the first oral therapy for all NTD thalassemia patients, including those with alpha- or beta-thalassemia,” said Ali Taher, M.D., Ph.D., Professor of Medicine, Hematology & Oncology and Director – Naef K. Basile Cancer Institute, American University of Beirut Medical Center in Beirut, Lebanon. “For NTD thalassemia patients across the globe, there are currently no approved oral treatments, and NTD thalassemia has consistently been associated with morbidity and mortality if left untreated. NTD thalassemia represents over half of clinically significant forms of thalassemia, so there is a tremendous unmet need. Based on the data reported to date, mitapivat has the potential to be a foundational treatment option for the thalassemia community.”

Agios is also advancing the fully enrolled Phase 3 ENERGIZE-T study of mitapivat in adults with transfusion-dependent alpha- or beta-thalassemia and expects to announce topline data from this 48-week study in mid-2024. Following the read-out of ENERGIZE-T, the company intends to file for regulatory approval of mitapivat as a treatment for thalassemia by the end of 2024, incorporating all available data from both studies.

Topline results for the Phase 3 ENERGIZE study were as follows:

• A total of 194 patients were enrolled in the study, with 130 randomized to mitapivat 100 mg twice-daily (BID) and 64 randomized to matched placebo. 122 (93.8%) in the mitapivat arm and 62 (96.9%) in the placebo arm completed the 24-week double-blind period of the study.

• The study met the primary endpoint of hemoglobin response. Hemoglobin response was defined as an increase of ≥1 g/dL in average hemoglobin concentrations from Week 12 through Week 24 compared with baseline

∗ Treatment with mitapivat demonstrated a statistically significant increase compared to placebo.

∗ 42.3% of patients in the mitapivat arm achieved a hemoglobin response, compared to 1.6% of patients in the placebo arm (2-sided p<0.0001).

• Treatment with mitapivat also demonstrated statistically significant improvements compared to placebo for both key secondary endpoints:

∗ Change from baseline in average FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) subscale score from Week 12 to Week 24.

∗ Change from baseline in average hemoglobin concentration from Week 12 to Week 24.

• Overall, during the 24-week double-blind period, incidence of adverse events was similar across mitapivat and placebo arms. Four (3.1%) subjects in the mitapivat arm experienced adverse events (AEs) leading to discontinuation; there were no AEs leading to discontinuation in the placebo arm.

Agios plans to present a more detailed analysis of the Phase 3 ENERGIZE data at an upcoming medical meeting.

About PYRUKYND® (mitapivat)

PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the United States, and for the treatment of PK deficiency in adult patients in the European Union.