PYRUKYND®

Update: 22 December 2025

• Topline results from the RISE UP Phase 3 trial announced.
• The primary endpoint of haemoglobin response was achieved with statistical significance.
• A second primary endpoint aiming to reduce the annual rate of pain crises was not met – the trial showed a reduction in the number of annual pain crises compared to placebo, but this was not statistically significant.
• Secondary endpoints for haemoglobin concentration and indirect bilirubin were achieved, whereas the change from baseline on PROMIS Fatigue was not met.

More specifically, the data showed that:

• 6% of patients achieved a haemoglobin response (defined as a ≥1.0 g/dL increase from baseline)
• In those patients who achieved a haemoglobin response, the mean change from baseline was a 1.6g/dL
• In those that achieved a haemoglobin response, the annual frequency of hospitalizations was 1.16 compared to 1.76 for non-responders
• Liver abnormalities that were observed were not suggestive of drug-induced hepatocellular injury (HCI), unlike what was observed in the mitapivat ENERGIZE and ENERGIZE-T Phase 3 trials.
• 3% of patients on mitapivat discontinued treatment due to adverse events.

The company plans to engage with the FDA ahead of a marketing application submission anticipated in the first quarter of 2026.

Sources: Agios Announces Topline Results from RISE UP Phase 3 Trial of Mitapivat in Sickle Cell Disease – Agios Pharmaceuticals, Inc.
Red Cell Revolution, Presentation of RISE UP Phase 3 Trial Results, 21 November 2025

Update: 30 September 2025

Topline results from RISE UP to be announced by the end of the year. Anticipated U.S. commercial launch in 2026

Source: Agios Reports Second Quarter 2025 Financial Results and Provides Business Update – Agios Pharmaceuticals, Inc.

Update: 30 June 2025

Data presented at the 30^th EHA Annual Congress (12–15 June) in Milan, Italy showed that of 10 SCD patients enrolled in the ESTIMATE study (Netherlands), 5 completed the Fixed Dose Extension Period (1 year) and the Prolonged Fixed Dose Extension Period (2 years) thus reporting a total of 3 years on mitapivat.

This demonstrated sustained efficacy and tolerability, evident (amongst other markers) increased Hb and improved renal outcomes.

Source: THREE-YEAR SAFETY, EFFICACY, AND RENAL OUTCOMES OF MITAPIVAT… – Kuppens G – EHA-3189 – Jun 12 2025

Update: 31 March 2025

No update available.

Update: 19 December 2024

• Completed enrollment of Phase 3 RISE UP study of mitapivat in sickle cell disease. Topline results to be shared in late 2025.
• European Commission designated mitapivat for the treatment of sickle cell disease as an orphan medicinal product.

New data:

• Data presented at the 66^th ASH Annual Congress (7 – 10 December 2024) in San Diego (USA) showed that tebapivat (mitapivat) was well tolerated in 16 patients with SCD receiving either 2mg or 5mg once daily for 28 days in the phase 1 study in adult pts with SCD (NCT04536792).

Sources: https://investor.agios.com/news-releases/news-release-details/agios-completes-enrollment-phase-3-rise-study-mitapivat-sickle
https://investor.agios.com/news-releases/news-release-details/agios-reports-business-highlights-and-third-quarter-2024
Results from a Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Tebapivat (AG-946) in Patients with Sickle Cell Disease

Update: 30 September 2024

No update available.

Update: 30 June 2024

At the 29^th EHA Annual Congress (13 – 16 June 2024) in Madrid (Spain):

• • The design of a phase 2 study to evaluate the effect of mitapivat in patients with SCD and nephropathy was presented. The primary objective is to achieve a ≥30% decrease of ACR from baseline within 6 months. Enrolment is expected to open in Q3 2024.
  • The design of the phase 3 portion of the RISE UP trial was reported, based on the results of the phase 2 dose-finding study that showed clinically meaningful improvements in haemoglobin response.
  • Mitapivat 100mg twice daily was selected as the dose for the phase 3 portion of the trial.
  • The primary objective will be a Hb response, defined as ≥1g/dL increase in weeks 24 – 52 compared to baseline. Enrolment is ongoing, with initiation expected in October 2023.

Sources: The Launch Of A Global, Phase 2, Open-Label, Multicenter, Single-Arm Study Of Mitapivat In Patients With Sickle Cell Disease And Nephropathy
Study Design Of The Phase 3 Portion Of Rise Up: A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Of Mitapivat In Patients With Sickle Cell Disease

Update: 31 March 2024

The company aims to complete enrolment for the Phase 3 portion of the RISE UP pivotal study of mitapivat in 2024.

Source: https://investor.agios.com/news-releases/news-release-details/agios-reports-fourth-quarter-and-full-year-2023-financial

Update: 20 December 2023

• First patient dosed in the Phase 3 portion of the RISE UP pivotal study of mitapivat.

New data

• Data presented at the 65^th ASH Annual Congress (9 – 12 December 2023) in San Diego (USA) showed that:
• A total of 79 patients were enrolled in the Phase 2 portion of the RISE UP study, with 26 patients in the 50 mg BID mitapivat arm, 26 patients in the 100 mg BID mitapivat arm, and 27 patients in the placebo arm.
• 2% of patients (n=12) in the 50 mg BID mitapivat arm and 50.0% of patients (n=13) in the 100 mg BID mitapivat arm achieved a hemoglobin response, defined as an increase of ≥1 g/dL in average hemoglobin concentrations from Week 10 through Week 12 compared with baseline.
• Of the 79 patients enrolled in the study, 73 continued into the Phase 2 open-label extension period.

Sources: https://investor.agios.com/news-releases/news-release-details/agios-reports-business-highlights-and-third-quarter-2023
https://investor.agios.com/news-releases/news-release-details/agios-presents-positive-results-phase-2-portion-rise-pivotal
https://ash.confex.com/ash/2023/webprogram/Paper187033.html

Update: 30 September 2023

No update available.

Update: 30 June 2023

Results from the RISE UP (phase 2) trial showed:

• Treatment with mitapivat demonstrated a statistically significant increase in hemoglobin response rate compared to placebo. Hemoglobin response was defined as an increase of ≥1 g/dL in average hemoglobin concentrations from Week 10 through Week 12 compared with baseline.
• 46.2% of patients (n=12) in the 50 mg twice daily (BID) mitapivat arm and 50.0% of patients (n=13) in the 100 mg BID mitapivat arm achieved a hemoglobin response.
• There were no adverse events (AEs) leading to discontinuation.

These results support proceeding with the Phase 3 part of the study. This is expected to enrol 198 patients, beginning in Oct-Dec 2023, reporting data in 2025 and receiving FDA approval in 2026.

Source: https://investor.agios.com/news-releases/news-release-details/agiosannounces-positive-results-phase-2-portion-rise-pivotal 

Update: 31 March 2023

• Completed enrollment in the Phase 2 portion of the RISE UP study of PYRUKYND® in adults with sickle cell disease.
• Anticipate to announce data and decision to move forward with Phase 3 by mid-year.

Source: https://investor.agios.com/news-releases/news-release-details/agiosreports-fourth-quarter-and-full-year-2022-financial