The US Food and Drug Administration (FDA) has granted orphan designation for AG-120 to treat patients with acute myeloid leukemia (AML) who harbor an isocitrate dehydrogenase-1 (IDH1) mutation.
AG-120 is an oral, selective inhibitor of the mutated IDH1 protein that is under investigation in two phase 1 clinical trials, one in hematologic malignancies and one in advanced solid tumors.
The FDA granted AG-120 fast track designation last month.
“Receiving orphan drug designation for AG-120 is an important milestone as we continue to move this program to late-stage development,” said Chris Bowden, MD, chief medical officer of Agios Pharmaceuticals, Inc., the company developing AG-120.
“We are pleased with the progress we are making in the clinic and look forward to presenting new data from our ongoing phase 1 study of AG-120 at the Congress of the European Hematology Association later this week.”
Phase 1 trial
Results from the phase 1 study of AG-120 in patients with hematologic malignancies were previously presented at the EORTC-NCI-AACR symposium in November 2014.
The data included 17 patients with relapsed and/or refractory AML who had received a median of 2 prior treatments. The patients were scheduled to receive AG-120 in 1 of 4 dose groups: 100 mg twice a day, 300 mg once a day, 500 mg once a day, and 800 mg once a day over continuous, 28-day cycles.
Of the 14 patients evaluable for response, 7 responded. Four patients achieved a complete response, 2 had a complete response in the marrow, and 1 had a partial response.
Responses occurred at all the dose levels tested. The maximum-tolerated dose was not reached. All responding patients were still on AG-120 at the time of presentation, and 1 patient with stable disease remained on the drug.
Researchers said AG-120 was generally well-tolerated. The majority of adverse events were grade 1 and 2. The most common of these were nausea, fatigue, and dyspnea.
Eight patients experienced serious adverse events, but these were primarily related to disease progression.
One patient experienced a dose-limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested, which improved to grade 1 with dose reduction. The patient was in complete remission and remained on AG-120 at the time of presentation.
There were 6 patient deaths, all unrelated to AG-120. Five deaths occurred after patients discontinued treatment due to progressive disease, and 1 patient died due to disease-related intracranial hemorrhage while on treatment.
About orphan designation
The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.
Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.
If the FDA approves AG-120 to treat patients with AML, orphan designation will provide Agios with 7 years of marketing exclusivity in the US.
