Agios Pharmaceuticals Announces Phase 3 ENERGIZE – Treatment for Thalassemia Patients


Agios Announces Phase 3 ENERGIZE Study of Mitapivat Met Primary Endpoint and Both Key Secondary Endpoints in Adults with Non-Transfusion-Dependent Alpha- or Beta-Thalassemia

January 3, 2024 – Agios Pharmaceuticals, Inc. today announced that the global Phase 3 ENERGIZE study of mitapivat in adults with non-transfusion-dependent (NTD) alpha- or beta-thalassemia achieved its primary endpoint of hemoglobin
response. Statistical significance was also achieved for both key secondary endpoints associated
with change from baseline in FACIT-Fatigue Score and hemoglobin concentration.

“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, said Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios.” 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.”

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.
o Treatment with mitapivat demonstrated a statistically significant increase
compared to placebo.
o 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:
o Change from baseline in average FACIT-Fatigue (Functional Assessment of
Chronic Illness Therapy-Fatigue) subscale score from Week 12 to Week 24.
o 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.

Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt
interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly
discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment
if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and
anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness
of breath.

Adverse Reactions: Serious adverse reactions occurred in 10% of patients receiving
PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture,
and musculoskeletal pain, each of which occurred in 1 patient. In the ACTIVATE trial, the most
common adverse reactions including laboratory abnormalities (≥10%) in patients with PK
deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased
(males), and arthralgia.

Drug Interactions:
• Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
• Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
• Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there
are no alternatives, adjust PYRUKYND dosage.
• Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives:
Avoid concomitant use with substrates that have narrow therapeutic index.
• UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic
• P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic

Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic

Please see full Prescribing Information and Summary of Product Characteristics for

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