A Study Evaluating the Efficacy and Safety of AG-348 in Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)

Summary

Study AG348-C-007 was a multicenter study designed to evaluate the efficacy and safety of treatment with AG-348 in a minimum of 20, with up to 40, participants with pyruvate kinase (PK) deficiency, who were regularly receiving blood transfusions. The study was composed of two parts. During Part 1, Dose Optimization Period, participants started on a dose of 5 mg AG-348 administered twice daily. Over the course of Part 1 each participant's dose of AG-348 was sequentially increased to 20 mg twice a day, followed by 50 mg twice a day depending on their tolerance. During Part 2, Fixed-Dose Period, participants received AG-348 at their optimized dose from Part 1.

Timeline

Start

2018-06-26

Primary completion

2020-11-12

Completion

2020-11-12

Outcome

Met primary endpoint

paper A reduction in transfusion burden by at least 33% was found in ten (37%) participants (95% CI 19-58; p=0·0002). PMID 35988546 ↗

release “The Phase 3 ACTIVATE-T trial of mitapivat achieved its primary endpoint.” agios.com ↗

release “Phase 3 ACTIVATE and ACTIVATE-T studies of mitapivat in adults with PK deficiency at European Hematology Association (EHA) Virtual Congress ; studies met primary and secondary endpoints” agios.com ↗

release “the ACTIVATE-T study met its primary endpoint, with 10 of 27 patients (37%; p=0.0002) receiving PYRUKYND ® achieving a transfusion reduction response” agios.com ↗

Publications

• Al-Samkari H, Grace RF, Glenthoj A, Andres O, Barcellini W, Galacteros F, Kuo KHM, Layton DM, Morado Arias M, Viprakasit V, Dong Y, Tai F, Hawkins P, Gheuens S, Morales-Arias J, Gilroy KS, Porter JB, van Beers EJ. Early-onset reduced bone mineral density in patients with pyruvate kinase deficiency. Am J Hematol. 2023 Mar;98(3):E57-E60. doi: 10.1002/ajh.26830. Epub 2023 Jan 9. No abstract available.
• Glenthoj A, van Beers EJ, Al-Samkari H, Viprakasit V, Kuo KHM, Galacteros F, Chonat S, Porter J, Zagadailov E, Xu R, Oluyadi A, Hawkins P, Gheuens S, Beynon V, Barcellini W; ACTIVATE-T investigators. Mitapivat in adult patients with pyruvate kinase deficiency receiving regular transfusions (ACTIVATE-T): a multicentre, open-label, single-arm, phase 3 trial. Lancet Haematol. 2022 Oct;9(10):e724-e732. doi: 10.1016/S2352-3026(22)00214-9. Epub 2022 Aug 18.
• Rab MAE, Van Oirschot BA, Kosinski PA, Hixon J, Johnson K, Chubukov V, Dang L, Pasterkamp G, Van Straaten S, Van Solinge WW, Van Beers EJ, Kung C, Van Wijk R. AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica. 2021 Jan 1;106(1):238-249. doi: 10.3324/haematol.2019.238865.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Mitapivat	Small molecule	—	Oral

Indications