Hepatitis case leads Agios to abandon congenital anemia drug

Lead PK activator AG-348 in phase 2 trial is unaffected, company says.

Agios has called time on one of its drug candidates for rare inherited disease pyruvate kinase (PK) deficiency—but stressed that the lead drug in the program is still on track.

The company said it halted development of PK activator AG-519 and pulled an application to start clinical trials after the FDA indicated it had place the drug under a clinical hold due to a case of cholestatic hepatitis in a patient taking the drug in a phase I trial. Cholestatic hepatitis occurs when bile secretion is impaired and is a recognized side effect of some medications. 

Agios' chief executive David Schenkein reassured investors on a conference call that lead PK activator AG-348 is unaffected, and the firm's ongoing phase 2 DRIVE PK trial of the drug is proceeding as planned.

"AG-348 and AG-519 are different molecules with different structures," said Schenkein. The company is now pushing ahead with plans for a pivotal program for first-in-class AG-348 that could potentially support marketing approval in adult PK deficiency patients.

In PK deficiency, mutations in the gene coding for the PK enzyme causes a form of hemolytic anemia, the accelerated destruction of red blood cells. There are no drugs currently to treat the disorder, which in some cases require patients to have lifelong blood transfusions. Its prevalence is around 51 cases per million in the population.

It's not the first time that shares in Agios have been affected by news on AG-519. Earlier this year, a poster presentation on the drug at the European Hematology Association (EHA) raised eyebrows after a case of class 2 thrombocytopenia or low platelet count was seen in an early-stage trial. 

On balance it seems to be a relatively minor setback for the 2009 Fierce 15 company, which is in the final stages of filing for approval of Celgene-partnered IDH2 inhibitor AG-221—another first-in-class dug—as a treatment for acute myeloid leukemia (AML).

Agios is also planning to file IDH1 inhibitor AG-120 for frontline AML in the first half of 2017. Agios has retained rights to that candidate, which is also being developed for myelodysplastic syndrome (MDS) and sold tumors.

Nevertheless, bad news typically spreads much more quickly than an explanation in biopharma, and shares in the company fell more than 19% after hours yesterday.