PYRUKYND®

Update: 22 December 2025

• CHMP Positive Opinion for new indication of PYRUKYND^® in adults with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia (Oct 2025) – awaiting European Commission approval for Marketing Authorisation (estimated for early 2026)
• FDA has approved AQVESME™ (mitapivat) for the treatment of anemia in adults with alpha- or beta-thalassemia. With this approved indication, AQVESME becomes the only FDA-approved medicine for anemia in both non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia.

Sources: U.S. FDA Approves Agios’ AQVESME™ (mitapivat) for the Treatment of Anemia in Adults with Alpha- or Beta-Thalassemia
Agios’ PYRUKYND® (mitapivat) Receives Positive CHMP Opinion for Adults with Thalassemia – Agios Pharmaceuticals, Inc.
Agios Reports Third Quarter 2025 Financial Results and Provides Business Update – Agios Pharmaceuticals, Inc.

Update: 30 September 2025

Approved for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia in Saudi Arabia.

PYRUKYND for adult TDT and NTDT (α- and β-thalassaemia) remains under active review by FDA, EMA, UAE.

FDA has extended the date by which they will issue a decision, known as the Prescription Drug User Fee Act (PDUFA) goal date, to 7 December 2025 following submission by the company of a proposed Risk Evaluation and Mitigation Strategy (REMS) to mitigate the risk of hepatocellular injury that was described in the application. The FDA has not requested new or additional efficacy or safety data.

Sources: Agios Provides Update on U.S. PDUFA Goal Date for PYRUKYND® (mitapivat) in Thalassemia – Agios Pharmaceuticals, Inc.
Agios’ PYRUKYND® (mitapivat) Approved for Adults with Thalassemia in Saudi Arabia – Agios Pharmaceuticals, Inc.
Agios Reports Second Quarter 2025 Financial Results and Provides Business Update – Agios Pharmaceuticals, Inc.

Update: 30 June 2025

No update available.

Update: 31 March 2025

FDA has accepted the regulatory application for mitapivat for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha or beta-thalassemia. Decision is anticipated by 7th September 2025.

Source: FDA Accepts Agios’ Supplemental New Drug Application for PYRUKYND® (mitapivat) in Adult Patients with Non-Transfusion-Dependent and Transfusion-Dependent Alpha- or Beta-Thalassemia – Agios Pharmaceuticals, Inc.

Update: 19 December 2024

Based on data observed in both the Phase 3 ENERGIZE and ENERGIZE-T studies, Agios filed regulatory applications for mitapivat for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassaemia with the U.S., European Union, Kingdom of Saudi Arabia and United Arab Emirates health authorities.

The Phase 3 ENERGIZE and ENERGIZE-T trials enrolled a total of 452 patients reflective of the real-world thalassemia population. The results demonstrated that mitapivat improves hemolytic anaemia and quality-of-life related measures, as measured by significant reductions in transfusion burden and significant improvements in hemoglobin and fatigue.

New data

• Data presented at the 66^th ASH Annual Congress (7 – 10 December 2024) in San Diego (USA) showed that:
  • Ex vivo treatment with mitapivat in 25 non-transfusion dependent thalassaemia patients (β-thal/HbE disease) in Thailand corresponded to reduced haemolysis and intracellular reactive oxygen species in RBCs thus corroborating clinical trial findings.

Sources: Agios Presents Positive Results from Phase 3 ENERGIZE-T Study of Mitapivat at ASH 2024 and Provides Regulatory Update on Mitapivat – Agios Pharmaceuticals, Inc.
Ex Vivo Treatment By Mitapivat, an Allosteric Pyruvate Kinase Activator, Reduced Hemolysis and Reactive Oxygen Species in Red Blood Cells of Non-Transfusion Dependent Hemolytic Anemic Patients Due to β-Thalassemia/Hb E Disease

Update: 30 September 2024

Submission to FDA for Supplemental New Drug Application (sNDA) anticipated by the end of 2024. Standard review time is 10 months, although Priority Review may reduce this to between 8 – 6 months.

Source: https://investor.agios.com/news-releases/news-release-details/agios-reports-business-highlights-and-second-quarter-2024

Update: 30 June 2024

• Data presented at the 29^th EHA Annual Congress (13 – 16 June 2024) in Madrid (Spain) showed that:
  – Mitapivat increased Hb in 42.3% of NTDT (α- and β-thalassaemia) patients, improving fatigue and walking capacity.
• FDA, EMA and GCC regulatory approval for TDT and NTDT will filed by the end of 2024.

Sources:
Agios Scientific Exchange Webinar, 21 June 2024
ENERGIZE: A Global Phase 3 Study of Mitapivat Demonstrating Efficacy and Safety in Adults with alpha- or beta-Non-Transfusion-Dependent Thalassaemia
Improvements in Fatigue and 6-minute Walk Test in  Adults with alpha- or beta-Non-Transfusion-Dependent Thalassaemia: The Phase 3 ENERGIZE Trial of Mitapivat 

Update: 31 March 2024

• The results of the Phase 3 ENERGIZE study of mitapivat in adults with non-transfusion-dependent (NTD) alpha- or beta-thalassemia showed that the study achieved its primary endpoint of hemoglobin response. The results in detail:
• 194 patients were enrolled in the study (130 randomized to mitapivat 100 mg twice-daily (BID) and 64 randomized to matched placebo).
• 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.
  • 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).
• 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.
• FDA regulatory approval for TDT and NTDT will filed by the end of 2024.

Sources: https://investor.agios.com/news-releases/news-release-details/agios-announces-phase-3-energize-study-mitapivat-met-primary
https://investor.agios.com/news-releases/news-release-details/agios-reports-fourth-quarter-and-full-year-2023-financial

Update: 20 December 2023

• Topline data from the two Phase 3 studies of mitapivat in non-transfusion-dependent and transfusion-dependent thalassemia will be announced in the first and second halves of 2024, respectively.

Source: https://investor.agios.com/news-releases/news-release-details/agios-reports-business-highlights-and-third-quarter-2023

Update: 30 September 2023

• Completed enrollment of the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND® in not regularly transfused and regularly transfused adults with thalassaemia, respectively.

Source: https://investor.agios.com/news-releases/news-release-details/agiosreports-business-highlights-and-second-quarter-2023

Update: 30 June 2023

• Screening of the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND ® in not regularly
  transfused and regularly transfused adults with thalassemia, respectively has been completed.

Source: Agios Reports Business Highlights and First Quarter 2023 Financial Results – Agios Pharmaceuticals, Inc.

Update: 31 March 2023

• Enrolled more than half of patients in the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND ® in not regularly transfused and regularly transfused adults with thalassemia, respectively.
• A clinical trial site for ENERGIZE and ENERGIZE-T (phase 3 clinical trials) for the 3 study of the safety and efficacy of PYRUKYND ® in non-transfusion dependent and transfusion-dependent thalassaemia patients respectively, have been initiated in Abu Dhabi.

The company aims to complete enrollment by mid-year.

Sources: https://investor.agios.com/news-releases/news-release-details/agios-reports-fourth-quarter-and-full-year-2022-financial
https://www.zawya.com/en/press-release/companies-news/ground-breaking-thalassemia-clinical-trials-to-begin-in-abu-dhabi-a0p9a3kg

Update: 22 December 2025

• Data presented at 67^th ASH Annual Congress (6 – 9 December 2025) in Orlando (USA) showed that:
  • 7/12 transfusion-dependent α-thalassaemia patients in the ENERGIZE-T trial achieved at least 50% reduction in transfused RBC units and more than 2 units reduction over 12 weeks compared to baseline
  • 6/12 transfusion-dependent α-thalassaemia patients in the ENERGIZE-T trial achieved transfusion independence for more than 8 consecutive weeks
  • 17 transfusion-dependent patients with α- or β-thalassaemia in the ENERGIZE-T open-label extension study were transfusion-free for an average of 30.49 weeks (including the trial and extension study) with a 56% reduction of annually required transfusion visits and 14.01 fewer transfusions per year that represented a 63.6% decrease from baseline.
• CHMP Positive Opinion for new indication of PYRUKYND^® in adults with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia (Oct 2025) – awaiting European Commission approval for Marketing Authorisation (estimated for early 2026)
• FDA has approved AQVESME™ (mitapivat) for the treatment of anemia in adults with alpha- or beta-thalassemia. With this approved indication, AQVESME becomes the only FDA-approved medicine for anemia in both non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia.

Sources: Efficacy of mitapivat in patients with transfusion-dependent alpha-thalassemia: Subgroup analysis from the ENERGIZE-T trial
Long-term transfusion-free duration and impact on transfusion-related burdens: Results from the ongoing ENERGIZE-T open-label extension study of mitapivat in transfusion-dependent alpha or beta-thalassemia
Agios’ PYRUKYND® (mitapivat) Approved for Adults with Thalassemia in Saudi Arabia – Agios Pharmaceuticals, Inc.
Agios’ PYRUKYND® (mitapivat) Receives Positive CHMP Opinion for Adults with Thalassemia – Agios Pharmaceuticals, Inc.
Agios Reports Third Quarter 2025 Financial Results and Provides Business Update – Agios Pharmaceuticals, Inc.

Update: 30 September 2025

Approved for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia in Saudi Arabia.

PYRUKYND for adult TDT and NTDT (α- and β-thalassaemia) remains under active review by FDA, EMA, UAE.
FDA has extended the date by which they will issue a decision, known as the Prescription Drug User Fee Act (PDUFA) goal date, to 7 December 2025 following submission by the company of a proposed Risk Evaluation and Mitigation Strategy (REMS) to mitigate the risk of hepatocellular injury that was described in the application. The FDA has not requested new or additional efficacy or safety data.

Sources: Agios Provides Update on U.S. PDUFA Goal Date for PYRUKYND® (mitapivat) in Thalassemia – Agios Pharmaceuticals, Inc.
Agios’ PYRUKYND® (mitapivat) Approved for Adults with Thalassemia in Saudi Arabia – Agios Pharmaceuticals, Inc.
Agios Reports Second Quarter 2025 Financial Results and Provides Business Update – Agios Pharmaceuticals, Inc.

Update: 30 June 2025

No update available.

Update: 31 March 2025

FDA has accepted the regulatory application for mitapivat for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha or beta-thalassemia. Decision is anticipated by 7th September 2025.

Source: FDA Accepts Agios’ Supplemental New Drug Application for PYRUKYND® (mitapivat) in Adult Patients with Non-Transfusion-Dependent and Transfusion-Dependent Alpha- or Beta-Thalassemia – Agios Pharmaceuticals, Inc.

Update: 19 December 2024

Based on data observed in both the Phase 3 ENERGIZE and ENERGIZE-T studies, Agios filed regulatory applications for mitapivat for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia with the U.S., European Union, Kingdom of Saudi Arabia and United Arab Emirates health authorities.

The Phase 3 ENERGIZE and ENERGIZE-T trials enrolled a total of 452 patients reflective of the real-world thalassemia population. The results demonstrated that mitapivat improves hemolytic anemia and quality-of-life related measures, as measured by significant reductions in transfusion burden and significant improvements in hemoglobin and fatigue.

New data

• Data presented at the 66^th ASH Annual Congress (7 – 10 December 2024) in San Diego (USA) showed that:
  • Mitapivat significantly improved haemoglobin levels and fatigue vs placebo in the phase 3 ENERGIZE-T trial in adults with transfusion-dependent α- or β-thalassaemia.
  • The primary endpoint was a transfusion reduction response defined by ≥ 50% reduction in transfused RBC units) was achieved by 30.4% of patients in the mitapivat arm.
  • Mitapivat significantly reduced transfusion burden and demonstrated a durable response of up to 36 weeks.

Sources: Agios Presents Positive Results from Phase 3 ENERGIZE-T Study of Mitapivat at ASH 2024 and Provides Regulatory Update on Mitapivat – Agios Pharmaceuticals, Inc.
ENERGIZE-T: A Global, Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Mitapivat in Adults with Transfusion-Dependent Alpha- or Beta-Thalassemia

Update: 30 September 2024

Submission to FDA for Supplemental New Drug Application (sNDA) anticipated by the end of 2024. Standard review time is 10 months, although Priority Review may reduce this to between 8 – 6 months.

Source: https://investor.agios.com/news-releases/news-release-details/agios-reports-business-highlights-and-second-quarter-2024

Update: 30 June 2024

Top-line results for the Phase 3 ENERGIZE-T study showed:

• 258 patients were enrolled in the study, with 171 randomized to mitapivat 100 mg twice-daily (BID) and 87 randomized to matched placebo.
• Primary endpoint of transfusion reduction response (TRR, defined as a ≥50% reduction in transfused red blood cell (RBC) units was met.
• 4% of patients achieved a transfusion reduction response in any 12-week period
• Overall, during the 48-week double-blind period, incidence of adverse events (AEs) was similar across mitapivat and placebo arms. In the mitapivat arm, 5.8% of the patients experienced an AE leading to discontinuation, compared to 1.2% of patients in the placebo arm.

FDA, EMA and GCC regulatory approval for TDT and NTDT will filed by the end of 2024.

Sources: Agios Scientific Exchange Webinar, 21 June 2024
TIF/Agios Webinar on Topline ENERGIZE-T Results, 10 June 2024
Agios Announces Phase 3 ENERGIZE-T Study of Mitapivat Met Primary Endpoint and All Key Secondary Endpoints in Adults with Transfusion-Dependent Alpha- or Beta-Thalassemia – Agios Pharmaceuticals, Inc.

Update: 31 March 2024

Top-line data from Phase 3 ENERGIZE-T study of mitapivat in adults with transfusion-dependent alpha- or beta-thalassemia are expected to be announced in mid-2024.

FDA regulatory approval for TDT and NTDT will filed by the end of 2024.

Sources: https://investor.agios.com/news-releases/news-release-details/agios-announces-phase-3-energize-study-mitapivat-met-primary
https://investor.agios.com/news-releases/news-release-details/agios-reports-fourth-quarter-and-full-year-2023-financial

Update: 20 December 2023

• Topline data from the two Phase 3 studies of mitapivat in non-transfusion-dependent and transfusion-dependent thalassemia will be announced in the first and second halves of 2024, respectively.

Source: https://investor.agios.com/news-releases/news-release-details/agios-reports-business-highlights-and-second-quarter-2023

Update: 30 September 2023

• Completed enrollment of the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND® in not regularly transfused and regularly transfused adults with thalassaemia, respectively.

Source: https://investor.agios.com/news-releases/news-release-details/agiosreports-business-highlights-and-second-quarter-2023

Update: 30 June 2023

• Screening of the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND ® in not regularly
  transfused and regularly transfused adults with thalassemia, respectively has been completed.

Source: Agios Reports Business Highlights and First Quarter 2023 Financial Results – Agios Pharmaceuticals, Inc.

Update: 31 March 2023

• Enrolled more than half of patients in the Phase 3 ENERGIZE and ENERGIZE-T studies of
  PYRUKYND ® in not regularly transfused and regularly transfused adults with thalassemia,
  respectively.
• A clinical trial site for ENERGIZE and ENERGIZE-T (phase 3 clinical trials) for the 4 study of the safety and efficacy of PYRUKYND ® in non-transfusion dependent and transfusion-dependent thalassemia patients respectively, have been initiated in Abu Dhabi.
• The company aims to complete enrolment by mid-year.

Sources: https://investor.agios.com/news-releases/news-release-details/agios-reports-fourth-quarter-and-full-year-2022-financial
https://www.zawya.com/en/press-release/companies-news/ground-breaking-thalassemia-clinical-trials-to-begin-in-abu-dhabi-a0p9a3kg