2020-12-03| R&DTrials & Approvals

Agios Pharmaceuticals’ Lead Candidate Mitapivat Achieves Primary Endpoint in ACTIVATE Trial

by Sangeeta Chakraborty
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Agios Pharmaceuticals announced positive results of the ACTIVATE Phase 3 trial that evaluated its lead candidate Mitapivat. The experimental drug succeeded in the first of two Phase 3 trials to treat a rare form of anemia due to pyruvate kinase deficiency (PKD). Following the announcement, Agios’ shares climbed about 6% on December 1st.

Mitapivat is an oral, small molecule activator of Pyruvate kinase-R (PKR) enzyme. Genetic mutation(s) in PK enzyme results in PKD, a rare hereditary condition that prevents the red blood cells (RBC) from converting blood sugar or glucose into energy. PK enzyme breaks down 2,3-DPG (2,3-diphosphoglycerate) and other compounds to produce cellular energy in a process known as glycolysis.

Mitapivat eliminates excessive 2,3 DPG and boosts energy production in RBCs by increasing PK activity—an action that prevents RBC destruction as well as hemoglobin molecules from sticking to each other (a feature of Sickle Cell Disease).



The company released only top-line results from the ACTIVATE trial but plans to discuss the specifics next year at a medical congress. The trial was done in two parts. Part 1 is a fixed-dose trial, while part 2 tested the drug in a dose-escalation study. Mitapivat led to sustained increases in hemoglobin concentration (≥1.5 g/dL) at two or more assessments at 16, 20, and 24 weeks, for 40% of treated patients, versus none on placebo during the fixed-dose period.

The data come from a study of 80 patients with PKD who don’t require blood transfusions. The safety profile observed in the study was generally consistent with previously reported data. There were no adverse events in the treatment arm, leading to discontinuation of the drug.

Mitapivat improved key secondary endpoints too, including change in Hb levels from baseline at Weeks 16, 20, and 24 during the fixed-dose period; markers of hemolysis; and markers of hematopoietic activity.

“The robust, clinically meaningful efficacy and safety results from the ACTIVATE study underscore mitapivat’s potential to be the first disease-modifying therapy for people with pyruvate kinase deficiency, a chronic, lifelong hemolytic anemia that often leads to serious physical and quality of life complications,” said Chris Bowden, M.D., Chief Medical Officer at Agios “With only supportive therapy currently available, there is tremendous unmet need in this community, and we are proud to advance a promising therapeutic candidate for these patients.”

Agios aims to file for mitapivat’s approval in PKD next year.


Mitapivat for SCD

A Phase 1 proof-of-concept trial, sponsored by Agios in collaboration with NIH, is currently investigating the safety, efficacy, and pharmacological properties of mitapivat in adults with SCD. It also expects to initiate a Phase 3, global, pivotal study of mitapivat in SCD in 2021. Meanwhile, Forma Therapeutics is developing a similar rival drug for SCD that should also enter phase 3 in 2021.

In addition to an active research and discovery pipeline across these three therapeutic areas, Agios has two approved oncology precision medicines (Idhifa and Tibsovo) and multiple first-in-class investigational therapies in clinical and/or preclinical development.

By Sangeeta Chakraborty, Ph.D.

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