A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)

Summary

Study AG348-C-006 evaluated the efficacy and safety of orally administered AG-348 as compared with placebo in participants with pyruvate kinase (PK) deficiency, who were not regularly receiving blood transfusions. Participants were randomized 1:1 to receive either AG-348 or a matching placebo.

Timeline

Start

2018-08-09

Primary completion

2020-10-09

Completion

2020-10-09

Outcome

Met primary endpoint

registry NUMBER Experimental: AG-348: 40.0 percentage of participants NCT03548220 ↗

registry Placebo Comparator: Placebo vs Experimental: AG-348; p <0.0001; Exact Cochran-Mantel-Haenszel; note: 2-sided p-value NCT03548220 ↗

release “global Phase 3 ACTIVATE trial of mitapivat in adults with pyruvate kinase (PK) deficiency who do not receive regular transfusions met its primary endpoint.” agios.com ↗

release “The Phase 3 ACTIVATE 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 study met its primary endpoint, with 40 percent of patients randomized to PYRUKYND ® achieving a hemoglobin response” agios.com ↗

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

Publications

• van Beers EJ, Al-Samkari H, Grace RF, Barcellini W, Glenthoj A, DiBacco M, Wind-Rotolo M, Xu R, Beynon V, Patel P, Porter JB, Kuo KHM. Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiency. Blood Adv. 2024 May 28;8(10):2433-2441. doi: 10.1182/bloodadvances.2023011743.
• Andrae DA, Grace RF, Jewett A, Foster B, Klaassen RJ, Salek S, Li J, Tai F, Boscoe AN, Zagadailov E. Psychometric validation of the Pyruvate Kinase Deficiency Diary and Pyruvate Kinase Deficiency Impact Assessment in adults in the phase 3 ACTIVATE trial. J Patient Rep Outcomes. 2023 Nov 9;7(1):112. doi: 10.1186/s41687-023-00650-3.
• 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.
• Al-Samkari H, Galacteros F, Glenthoj A, Rothman JA, Andres O, Grace RF, Morado-Arias M, Layton DM, Onodera K, Verhovsek M, Barcellini W, Chonat S, Judge MP, Zagadailov E, Xu R, Hawkins P, Beynon V, Gheuens S, van Beers EJ; ACTIVATE Investigators. Mitapivat versus Placebo for Pyruvate Kinase Deficiency. N Engl J Med. 2022 Apr 14;386(15):1432-1442. doi: 10.1056/NEJMoa2116634.
• 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	5 mg	Oral
Subject	Mitapivat	Small molecule	20 mg	Oral
Subject	Mitapivat	Small molecule	50 mg	Oral

Indications