Agios Initiates Phase 1 Study of AG-348, a First-in-class PKR Activator, for Pyruvate Kinase Deficiency

In Press Release by Cameron

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  • First Agios Clinical Program in Inborn Errors of Metabolism 

  • Third Agios Program to Enter Clinic in Less than a Year

April 17, 2014

Agios Pharmaceuticals, Inc., a leader in the fields of cancer metabolism and inborn errors of metabolism (IEM), today announced dose administration of AG-348 in a Phase 1 study in healthy volunteers. AG-348 is an orally available, potent, selective small molecule activator of pyruvate kinase-R (PK-R), a metabolic enzyme, which, when mutated, leads to pyruvate kinase (PK) deficiency, a rare, inherited hemolytic anemia. There is substantial unmet need among patients with PK deficiency as there is no therapy available to treat the underlying disease. AG-348 is wholly owned by Agios, with the company maintaining full worldwide development and commercialization rights.

“Today’s announcement marks the initiation of our first clinical program in IEMs and our third as a company,” said David Schenkein, M.D., chief executive officer of Agios. “Agios believes in the potential of small molecules to become disease-modifying therapeutics for rare genetic disorders by targeting the specific metabolic defects driving these diseases. We expect that the results from this healthy volunteer study will enable us to move AG-348 rapidly into a study in patients with PK deficiency.”

“Preclinical studies have demonstrated that AG-348 activates a broad spectrum of PK-R mutant proteins, and corrects the metabolic defects found in patient-derived blood samples,” said Scott Biller, chief scientific officer of Agios. “These data support the hypothesis that drug intervention with AG-348 will restore glycolytic pathway flux and normalize red blood cell metabolism. Because AG-348 directly targets the underlying disease, it has the potential to be an important treatment option for patients with PK deficiency.”

About the Study

The Phase 1, single-center, randomized, double-blind, placebo-controlled clinical trial will assess the safety and tolerability of AG-348 through dose escalation in healthy adult men and women. Key objectives of the trial include characterizing the safety, pharmacokinetic and pharmacodynamic relationships of AG-348 and select metabolic biomarkers. Please refer to for additional clinical trial details.

About Pyruvate Kinase (PK) Deficiency

PK deficiency is a rare inherited disease that presents as hemolytic anemia due to the accelerated destruction of red blood cells (RBCs). PK deficiency is caused by mutations that affect the activity of the metabolic enzyme PK-R, the form of pyruvate kinase that is present in RBCs. The current standard of care for PK deficiency is supportive, including blood transfusions, splenectomy, chelation therapy to address iron overload and/or interventions for other treatment- and disease-related morbidities. Currently, there is no approved therapy to treat the underlying cause of PK deficiency.

About Agios Pharmaceuticals, Inc.

Agios Pharmaceuticals is focused on discovering and developing novel drugs to treat cancer and inborn errors of metabolism, or IEMs, which are rare genetic metabolic diseases, through scientific leadership in the field of cellular metabolism. In addition to an active research and discovery pipeline across both therapeutic areas, Agios has multiple first-in-class lead product candidates in cancer metabolism and IEMs in clinical and/or preclinical development. All Agios programs focus on genetically identified patient populations, leveraging our knowledge of metabolism, biology and genomics. For more information, please visit our website at