Agios Pharmaceuticals Initiates Multiple Ascending Dose Trial in Healthy Volunteers of AG-348 for the Potential Treatment of PK Deficiency, a Rare, Hemolytic Anemia

In Press Release by Cameron

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Initial Safety and Pharmacokinetic Findings From Single Ascending Dose Trial Support Early Advancement

June 09, 2014

Agios Pharmaceuticals, Inc., a leader in the fields of cancer metabolism and inborn errors of metabolism (IEMs), today announced the initiation of a multiple ascending dose (MAD) Phase 1 trial of AG-348 in healthy volunteers. This study is designed to characterize the safety, tolerability, pharmacokinetics and pharmacodynamics of increasing doses of AG-348 for 14 days. AG-348 is a novel, first-in-class, orally available activator of pyruvate kinase-R (PKR) for the treatment of pyruvate kinase (PK) deficiency, a rare, hemolytic anemia. This trial was initiated based on data from the ongoing single ascending dose (SAD) Phase 1 trial, in which AG-348 has been determined to be well tolerated to date. The SAD study began in April 2014 and has completed dosing of more than half of the planned cohorts. Data from both studies are expected to be presented at a medical conference in 2015.

“AG-348 represents a completely new approach to treating patients with PK deficiency, a serious form of inherited hemolytic anemia with no approved therapy that targets the metabolic defect responsible for the underlying disease,” said David Schenkein, M.D., chief executive officer of Agios. “We are pleased to be moving forward with the MAD study that will allow us to further characterize the product candidate and establish the dose ranges we will study in patients with PK deficiency.”

Preclinical studies have demonstrated that AG-348 activates a broad spectrum of PKR mutant proteins, and corrects the metabolic defects found in patient-derived blood samples. AG-348 is currently the only drug candidate being evaluated for the potential of correcting metabolic defects found in 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 multiple ascending doses 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 for additional clinical trial details.

About Pyruvate Kinase (PK) Deficiency, a Rare, Inherited Hemolytic Anemia

Pyruvate kinase (PK) deficiency, a rare, inherited hemolytic anemia affecting children and adults, is caused by mutations that affect the activity of the metabolic enzyme pyruvate kinase-R (PKR), the form of pyruvate kinase that is present in red blood cells. 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. AG-348 is a first-in-class orally available, potent, selective small molecule activator of PKR, which, when mutated, leads to PK deficiency. AG-348 was discovered in the laboratory of Agios, and the company retains worldwide development and commercialization rights.

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