Agios Pharmaceuticals, a renowned public American pharmaceutical firm aimed at developing small-molecule anti-cancer therapeutics, reportedly announced that it established clinical proof-of-concept for AG-348 (mitapivat) on the basis of Phase 2 trial results.
The Phase 2 trial was conducted on patients suffering from non-transfusion-dependent thalassemia. AG-348 (mitapivat) is a first-in-class, investigational, oral and small molecule wild-type allosteric activator and a varied array of mutated PKR (pyruvate kinase-R) enzymes.
The Phase 2 trial has signed up 12 of the 17 intended patients (three with α-thalassemia and nine with β-thalassemia). Since the data cutoff date, November 14, 2019, eight patients, all diagnosed with β-thalassemia, were deemed evaluable for the hemoglobin increase primary endpoint of ≥1.0 g/dL from baseline in a minimum of one assessment between weeks 4 to 12.
All eight participants were administered 50 mg of AG-348 twice a day during the initial six weeks. This dose was increased to 100 mg two times a day after with all patients being on treatment (range between 12.4-34.3 weeks).
The results showed that seven out of the total eight patients that were efficacy evaluable gained a hemoglobin rise of ≥1.0 g/dL, and for the responders, the average growth in hemoglobin from baseline was seen to be 1.76 g/dL (range, 0.9–3.3 g/dL) at weeks 4-12.
Most of the adverse events were observed to be Grade 2 or 1 and consistent with Phase 2 results that were previously published for AG-348 in patients with PK (pyruvate kinase) deficiency. Updated outcomes collected in the Phase 2 thalassemia trial would be showcased at a clinical meeting mostly in the first two quarters of 2020.
Chief Medical Officer at Agios, Chris Bowden, M.D. stated that these data show the proof of concept of wild type PKR activation being capable of conveying clinical benefit in blood disorder of thalassemia and offers compelling evidence to expand the clinical development of mitapivat in the disease.
Bowden further added that the tolerability and safety profile that was observed in this study and adults that are pyruvate kinase deficient supports the uninterrupted investigation of mitapivat therapy across lifelong hemolytic, severe anemias like sickle cell disease, thalassemia and pyruvate kinase deficiency.
Recently, the company also showcased outcomes from Single Agent Dose escalation arm of Phase 1 trial of AG 270.