Agios Announces Clinical Proof-of-Concept in Phase 2a Trial of AG-946 for the Treatment of Anemia in Lower-Risk Myelodysplastic Syndromes - Seite 2

A total of 22 patients enrolled in the Phase 2a portion of the study, including 12 classified as non-transfused (NTD) and 10 classified as LTB. Of the 22 patients enrolled in Phase 2a, 19 patients elected to continue to the extension period. Agios intends to complete a full evaluation of the Phase 2a data and assess the impact on the Phase 2b portion of the protocol, and present results of the Phase 2a portion of the study at a medical meeting in 2024.

Phase 2a Design
The open-label, proof-of-concept, Phase 2a portion of the study was designed to evaluate the safety and efficacy of AG-946 in adults with anemia due to lower-risk MDS. Patients with a documented diagnosis of MDS were eligible for the study if they met the Revised International Prognostic Scoring System (IPSS-R) classification of lower-risk disease (risk score: ≤3.5) and <5% blasts, as determined by the participant’s bone marrow biopsy/aspirate during the screening period, and if their hemoglobin concentration measured <11.0 g/dL during the 4-week screening period. Participants were classified as non-transfused (NTD) if they had received <3 red blood cell (RBC) units in the 16-week period before administration of the first dose of study drug and no transfusions in the 8-week period before administration of the first dose of study drug, or low transfusion burden (LTB) if they had received 3 to 7 RBC units in the 16-week period before administration of the first dose of study drug and <4 RBC units in the 8-week period before administration of the first dose of study drug. Participants with a high transfusion burden were not eligible for the Phase 2a portion of the study.

Participants received 5mg of oral AG-946 once daily for up to 16 weeks in the core period. At the discretion of the investigator, participants who completed the core period of the study are eligible to receive the same dose in an extension period for up to 156 weeks.

The two primary endpoints of the study were transfusion independence (for participants classified as LTB), defined as transfusion-free for ≥8 consecutive weeks during the core period, and hemoglobin response, defined as a ≥1.5 g/dL increase from baseline in the average hemoglobin concentration from Week 8 through Week 16.

Next month, Agios and its collaborators are presenting preclinical data supporting its MDS clinical development program – as well as additional data across the company’s additional therapeutic areas of focus, including PK deficiency, thalassemia and sickle cell disease – at the American Society of Hematology (ASH) Annual Meeting, which is being held December 9-12, 2023, in San Diego.