Clinical trial updates

Mitapivat (AG-348)


Update: 08 January 2021 

Interim data was presented at ASH2020:

  • 12/13 evaluable patients have achieved a Hb increase of more than ≥ 1.0 g/dL after a median of 3.1 wks. This included 4/4 patients with α-thalassemia and 8/9 pts with β-thalassemia.
  • 13 pts had completed 12 wks of treatment and were evaluable for the primary endpoint.
  • 9/13 patients had completed 24 wks of treatment, all with β-thalassemia. Among this group, mean increase of Hb was 1.43 g/dL.
  • Final results from this Phase 2 trial will be announced in 2021.
  • A Phase 3 pivotal program evaluating mitapivat in thalassemia, including both α-and β-thalassemia, as well as transfusion dependent and non-transfusion dependent patient populations, is expected to initiated in

Sources: updated-data-phase-1-study-mitapivat-first-class


Update: 05 November 2020

Interim data will be presented at the 62nd ASH Meeting in December 2020.



Update: 25 August 2020

  • FDA Orphan Drug Designation Granted to Mitapivat for Treatment of Thalassemia
  • The ongoing, open-label Phase 2 study is evaluating the efficacy, safety, pharmacokinetics and pharmacodynamics of mitapivat treatment in adults with non-transfusion-dependent α- and β-thalassaemia who have a baseline hemoglobin (Hb) concentration of ≤10 g/dL. The trial is fully enrolled with 20 patients, and includes a 24-week core period followed by a 2-year extension period for eligible participants. All patients were treated with an initial dose of mitapivat 50 mg twice daily followed by a dose-level increase to 100 mg twice daily at the week 6 visit based on safety evaluations and Hb concentrations.
  • Interim data from the ongoing Phase 2 study evaluating single agent mitapivat in non-transfusion-dependent α- and β-thalassaemia were presented in an oral presentation at the 25th European Hematology Association Annual Congress showing that:
    • 12/13 (92.3%) evaluable patients including all 4 (100%) α-thalassaemia patients and 8 of 9 (88.9%) patients with β-thalassaemia met the primary endpoint defined as a ≥1.0 g/dL increase in Hb concentration (for at least one assessment in the initial 12 week period). Mean Hb change was 1.34 g/dL.
    • 8/9 patients sustained this Hb increase throughout a subsequent 12 week period (total 24 weeks).



Update: 31 May 2020

Data on 13 patients (from a total enrolment of 20 patients) from the Phase 2 proof-of-concept study of Mitapivat in alpha and beta thalassaemia will be presented at the EHA25 Congress in June.



Update: 31 March 2020

No update available.


Update: 31 January 2020

  • The clinical proof-of-concept has been established based on a preliminary analysis of the Phase 2 trial of Mitapivat (AG-348) in patients with non-transfusion-dependent thalassaemia announced at the 61st Annual Meeting of the American Society of Haematology.
  • The Phase 2 study has enrolled 12 of the intended 17 patients (nine with β-thalassaemia and three with α-thalassaemia).
  • The primary endpoint has been set as a haemoglobin increase of 0 g/dL from baseline in at least one assessment during Weeks 4-12.
  • All β-thalassaemia patients were treated with 50 mg of Mitapivat twice daily for the first six weeks and escalated to 100 mg twice daily, and all patients remain on treatment (range 12.4-34.3 weeks).
  • 8/9 β-thalassaemia patients who were evaluable, of these 7 patients achieved a haemoglobin increase of 0 g/dL, and for responders the mean haemoglobin increase from baseline was 1.76 g/dL (range, 0.9–3.3 g/dL) during Weeks 4-12.
  • Updated results from the Phase 2 thalassaemia study will be presented at a medical meeting in the first half of 2020.



Update: 25 November 2019

No update available.


Update: 27 September 2019

DRIVE PK is an ongoing global, open-label, Phase 2, safety and efficacy study evaluating Mitapivat in adults with PK deficiency who do not receive regular transfusions. It is the first clinical trial in adults with PK deficiency.

Mitapivat is an investigational, first-in-class, oral, small molecule allosteric activator of wild-type and a variety of mutated pyruvate kinase-R (PKR) enzymes that directly targets the underlying metabolic defect in PK deficiency, a rare, potentially debilitating, haemolytic anemia.

Methodology: Patients were randomly assigned to receive either 50 mg or 300 mg of Μitapivat twice daily for a 24-week core period and eligible patients could continue treatment in an ongoing extension phase.


  • Data from the study demonstrated rapid, clinically significant increases in haemoglobin in 50 percent of patients, and for patients in the extension phase, the response was sustained for up to 35 months
  • 26 of 52 patients (50%) achieved a clinically significant maximum haemoglobin increase of >1.0 g/dL

Based on these results the investigator industry has moved forward to conduct a proof-of-concept clinical trial of Μitapivat for the treatment of NTDT.

 DRIVE PK consists of two ongoing global trials in adults with PK deficiency that are on track to complete enrollment by year-end 2019:

  • ACTIVATE: A placebo-controlled trial with a 1:1 randomization, expected to enroll approximately 80 patients who do not receive regular transfusions, with an aim to achieve a sustained haemoglobin increase of ≥1.5 g/dL.
  • ACTIVATE-T: A single arm trial of up to 40 regularly transfused patients with an aim to reduce the transfusion burden over six months compared to individual historical transfusion burden over prior 12 months.


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