The US Food and Drug Administration (FDA) has granted fast track designation to AG-120 for the treatment of patients with acute myelogenous 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.
Data from the phase 1 trial in hematologic malignancies were previously presented at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in November 2014.
Updated data from this trial are scheduled to be presented at the 20th Annual Congress of the European Hematology Association (EHA) next month.
About fast track designation
The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.
“We are pleased that now both AG-120 and AG-221 have been granted fast track designation, demonstrating the FDA’s commitment to facilitate the development and expedite the review of our lead IDH programs as important new therapies for people with AML who carry these mutations,” said Chris Bowden, MD, chief medical officer of Agios Pharmaceuticals, Inc., the company developing AG-120 in cooperation with Celgene Corporation.
Phase 1 results
At the EORTC-NCI-AACR symposium, researchers presented results from the ongoing phase 1 trial of AG-120 in hematologic malignancies. 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.
“We look forward to presenting new data from the ongoing phase 1 study at the EHA Annual Congress next month,” Dr Bowden said, “and remain on track to initiate a global, registration-enabling, phase 3 study in collaboration with Celgene in AML patients who harbor an IDH1 mutation in the first half of 2016.”
