Phase 2a/2b Study of AG-946 in Patients with Anaemia Due to Lower-Risk Myelodysplastic Syndromes

  • Research type

    Research Study

  • Full title

    A Phase 2a/2b, Open-label, Proof of Concept (Phase 2a) and Double-blind, Randomized, Placebo-Controlled (Phase 2b), Multicenter, Efficacy, and Safety Study of AG-946 in Participants With Anemia Due to Lower-Risk Myelodysplastic Syndromes



  • Contact name

    María Trolliet

  • Contact email

  • Sponsor organisation

    Agios Pharmaceuticals, Inc.

  • ISRCTN Number


  • Identifier


  • Research summary

    Myelodysplastic Syndromes (MDS) are a group of rare haematological malignancies characterised by ineffective haematopoiesis (process by which the body produces blood cells and blood plasma), progressive cytopenia (a condition in which there is a lower-than-normal number of blood cells) and abnormal cellular maturation. Anaemia is the most common cytopenia in MDS which leads to symptoms such as fatigue that can impact normal daily lives. Approximately 50% of all MDS patients require regular red blood cell (RBC) transfusions. However, RBC transfusions do not completely alleviate health-related quality of life aspects, they contribute to iron overload and lead to substantial human and financial burden.

    The investigational drug, AG-946, is a novel small molecule that activates the enzyme pyruvate kinase which contributes to the production of energy in the RBC. By helping to increase energy, RBC functionally and survival may be improved. Preclinical studies have demonstrated that AG-946 has high potency, a pharmacokinetic half-life that supports once-daily administration, a long duration of pharmacodynamic activity, and no observed off target effects, suggesting that AG-946 has the potential to improve ineffective erythropoiesis and thus anaemia due to MDS.

    As such, the Sponsor Agios Pharmaceuticals, Inc. designed this Phase 2a/2b study with a purpose to determine the safety, tolerability and efficacy of AG-946 when administered with standard treatment for anaemia due to MDS. There are 2 parts in this study - Phase 2a and Phase 2b. In Phase 2a, about 20 participants will take part, which will test 1 dose level (5mg once daily) of AG-946. This part is open-label and the study duration will be up to 180 weeks. In Phase 2b, about 96 participants will take part, which will test 3 dose levels (2mg, 3mg, or 5mg once daily) of AG-946. This part is double-blinded and the study duration will be up to 188 weeks.

  • REC name

    North West - Liverpool Central Research Ethics Committee

  • REC reference


  • Date of REC Opinion

    7 Oct 2022

  • REC opinion

    Further Information Favourable Opinion