The Phase I study is a single-center, double-blind trial designed to evaluate the safety and tolerability of AG-348 through dose escalation in healthy adult men and women.
The key objectives of the randomized, placebo-controlled trial includes characterizing the safety, pharmacokinetic and pharmacodynamic relationships of AG-348 and select metabolic biomarkers.
Agios CEO Dr David Schenkein noted this announcement marks the initiation of the company’s first clinical program in IEMs and its third as a company.
"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," Dr Schenkein added.
Agios chief scientific officer Scott Biller noted that 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.
"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," Biller added.
Pyruvate kinase deficiency is a rare, inherited hemolytic anemia. The deficiency is caused due to mutation in pyruvate kinase-R, a metabolic enzyme.
Agios owns AG-348 and the company is maintaining full worldwide development and commercialization rights for the drug.