Agios Provides Update on U.S. PDUFA Goal Date for PYRUKYND® (mitapivat) in Thalassemia

Rhea-AI Summary

Agios Pharmaceuticals (Nasdaq: AGIO) announced that the FDA has extended the PDUFA goal date for PYRUKYND® (mitapivat) by three months, from September 7, 2025, to December 7, 2025. The extension follows Agios's submission of a proposed Risk Evaluation and Mitigation Strategy (REMS) to address hepatocellular injury risk.

The REMS submission is considered a major amendment to the supplemental New Drug Application (sNDA) for PYRUKYND®, which aims to treat adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia. The extension is not related to new safety or efficacy data. The sNDA is supported by results from the ENERGIZE and ENERGIZE-T Phase 3 trials.

Positive

• PYRUKYND® could potentially become a disease-modifying oral medicine for thalassemia patients
• No new safety or efficacy concerns raised by FDA
• Company maintains collaborative engagement with FDA

Negative

• PDUFA date delayed by three months
• Risk of hepatocellular injury requiring REMS implementation
• Additional regulatory requirements could delay market entry

• PDUFA goal date extended by three months from September 7, 2025, to December 7, 2025
  

CAMBRIDGE, Mass., Sept. 04, 2025 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a commercial-stage biopharmaceutical company focused on delivering innovative medicines for patients with rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) goal date for the supplemental New Drug Application (sNDA) of PYRUKYND^® (mitapivat), an oral pyruvate kinase (PK) activator, for the treatment of adult patients with non-transfusion-dependent (NTD) and transfusion-dependent (TD) alpha- or beta-thalassemia by three months to December 7, 2025. 

Following a recent information request from the FDA, Agios submitted a proposed Risk Evaluation and Mitigation Strategy (REMS) to mitigate the risk of hepatocellular injury that was described in the original PYRUKYND sNDA. The submission of the REMS is a major amendment to the PYRUKYND sNDA, resulting in a three-month review extension. This extension is not the result of new or additional efficacy or safety data requested by the FDA or submitted by Agios.

“We remain confident in the favorable benefit-risk profile of PYRUKYND in thalassemia,” said Brian Goff, Chief Executive Officer, Agios. “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.”

The PYRUKYND sNDA is supported by results from the global, randomized, double-blind, placebo-controlled ENERGIZE and ENERGIZE-T Phase 3 trials in adults with NTD and TD alpha- or beta-thalassemia, respectively.

About Thalassemia
Thalassemia is a rare, inherited blood disease that affects the production of hemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body. The disease is categorized into two main types: alpha-thalassemia and beta-thalassemia, depending on which globin chain of the hemoglobin is affected. By disrupting hemoglobin production, thalassemia reduces the number of circulating red blood cells and shortens their lifespan, which leads to anemia, fatigue and serious complications.

Some individuals with thalassemia require regular transfusions (classified as transfusion-dependent thalassemia), while others only need them intermittently (classified as non-transfusion-dependent thalassemia). All patients with thalassemia experience a significant disease burden, including comorbidities, reduced quality of life and shortened life expectancy.  

In the U.S., approximately 6,000 adult patients are diagnosed with thalassemia.  

About ENERGIZE and ENERGIZE-T
ENERGIZE (NCT04770753) and ENERGIZE-T (NCT04770779) are global, randomized, double-blind, placebo-controlled Phase 3 trials evaluating the efficacy and safety of mitapivat in adults with alpha- or beta-thalassemia.

The ENERGIZE trial randomized 194 non-transfusion-dependent patients 2:1 to receive either mitapivat 100 mg twice daily or placebo. The primary endpoint was the proportion of patients achieving a hemoglobin response, defined as an increase of ≥1.0 g/dL in average hemoglobin concentrations from week 12 through week 24 compared with baseline. Key secondary endpoints included changes from baseline in Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT-Fatigue) scores and in average hemoglobin concentration from week 12 to week 24. The study also assessed safety and tolerability.

The ENERGIZE-T trial randomized 258 transfusion-dependent patients 2:1 to receive either mitapivat 100 mg twice daily or placebo. The primary endpoint was the proportion of patients achieving a transfusion reduction response (TRR), defined as a ≥50% reduction in transfused red blood cell (RBC) units with a reduction of ≥2 units of transfused RBCs in any continuous 12-week period through week 48. Several additional transfusion reduction measures were included as key secondary endpoints, and achievement of transfusion independence was a secondary endpoint. The study also assessed safety and tolerability.

About PYRUKYND^® (mitapivat)
U.S. INDICATION
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.

U.S. IMPORTANT SAFETY INFORMATION
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.

Hepatocellular Injury in Another Condition: In patients with another condition treated with PYRUKYND at a higher dose than that recommended for patients with PK deficiency, liver injury has been observed. These events were characterized by a time to onset within the first 6 months of treatment with peak elevations of alanine aminotransferase of >5× upper limit of normal (ULN) with or without jaundice. All patients discontinued treatment with PYRUKYND, and these events improved upon treatment discontinuation.

Obtain liver tests prior to the initiation of PYRUKYND and monthly thereafter for the first 6 months and as clinically indicated. Interrupt PYRUKYND if clinically significant increases in liver tests are observed or alanine aminotransferase is >5x ULN. Discontinue PYRUKYND if hepatic injury due to PYRUKYND is suspected.

Adverse Reactions: 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 index.
• P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.

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

Please see full Prescribing Information for PYRUKYND.

About Agios: Fueled by Connections to Transform Rare Diseases™
At Agios, our vision is to redefine the future of rare disease treatment. Fueled by connections, we build trusted partnerships with communities – collaborating to develop and deliver innovative medicines that have the potential to transform lives. With a foundation in hematology, we combine biological expertise with real-world insights to advance a growing pipeline of rare disease medicines that reflect the priorities of the people we serve. Agios is a commercial-stage biopharmaceutical company headquartered in Cambridge, Massachusetts. To learn more, visit www.agios.com and follow us on LinkedIn and X.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Agios’ communications with FDA with respect to the PYRUKYND sNDA, including its submission of a proposed REMS; its planned further engagements with FDA; and other statements regarding Agios’ strategic plans, objectives and focus. The words “anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios’ current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios’ product candidates will successfully continue. There can be no guarantee as to the disposition of Agios’ sNDA for PYRUKYND in thalassemia. There can be no guarantee that any positive developments in Agios’ business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation: risks and uncertainties related to the impact of pandemics or other public health emergencies to Agios’ business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Agios’ results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Agios’ ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Agios' ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; Agios’ ability to establish and maintain key collaborations; uncertainty regarding any royalty payments related to the sale of its oncology business or any milestone or royalty payments related to its in-licensing of AG-236, and the uncertainty of the timing of any such payments; uncertainty of the results and effectiveness of the use of Agios’ cash and cash equivalents; and general economic and market conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

Contacts:
Investor Contact
Morgan Sanford, Vice President, Investor Relations
Agios Pharmaceuticals
morgan.sanford@agios.com

Media Contact
Eamonn Nolan, Senior Director, Corporate Communications
Agios Pharmaceuticals
eamonn.nolan@agios.com

FAQ

What is the new PDUFA date for Agios's PYRUKYND® (AGIO) thalassemia treatment?

The FDA has extended the PDUFA date for PYRUKYND® to December 7, 2025, a three-month extension from the original date of September 7, 2025.

Why did the FDA extend the review period for Agios's PYRUKYND®?

The extension was due to Agios submitting a proposed Risk Evaluation and Mitigation Strategy (REMS) to address the risk of hepatocellular injury, which constituted a major amendment to the sNDA.

What patient population is PYRUKYND® targeting for Agios (AGIO)?

PYRUKYND® is targeting adult patients with non-transfusion-dependent (NTD) and transfusion-dependent (TD) alpha- or beta-thalassemia.

What clinical trials support the PYRUKYND® sNDA submission?

The sNDA is supported by results from the ENERGIZE and ENERGIZE-T Phase 3 trials, which were global, randomized, double-blind, placebo-controlled studies in adults with NTD and TD thalassemia.

What safety concerns were identified for PYRUKYND® in the thalassemia application?

The FDA identified a risk of hepatocellular injury, which required Agios to submit a Risk Evaluation and Mitigation Strategy (REMS) to address this safety concern.