News Feature | December 3, 2014

New Acute Myeloid Leukemia Drug Shows Positive Phase 1 Trial Results

By C. Rajan, contributing writer

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Scientists at the University of Colorado Cancer Center have announced the "extremely promising" results from a phase 1 clinical trial for investigational drug AG-120 in acute myeloid leukemia (AML) patients with IDH1 gene mutations.

The results were presented at the 26th European Organization for Research and Treatment of Cancer Symposium in Barcelona on Nov 19th.

The clinical trial was led by Dr. Daniel Pollyea at the University of Colorado Cancer Center. The Phase 1 study enrolled AML patients who had relapsed after previous treatments. Out of the 14 patients, seven responded well to escalating doses of AG-120, and of these seven, there were four cases of complete remission.

"This is one of the most exciting developments in AML in a long time," Dr. Pollyea says. "This is a high-risk population, and we hope that with continued successes we'll be able to offer this therapy to more and more patients participating in this clinical trial."

AG-120 is a first-in-class, oral, selective, inhibitor of the mutant isocitrate dehydrogenase-1 (IDH1) enzyme. AG-120 is developed by Agios Pharmaceuticals in collaboration with Celgene Corporation.

Based on these positive Phase 1 results, Agios plans to advance into the next phase of development by starting multiple expansion cohorts at a fixed dose in early 2015.

The results of this trial correlate with the findings from the phase 1 study of a related drug, AG-221, which works against IDH2 mutations. This drug candidate, also from Agios, was granted the FDA’s Fast Track designation in August based on positive Phase 1 data. Agios expects a similar outcome for the sister drug, AG-120.

IDH1 and IDH2 are two metabolic enzymes that help to break down nutrients and generate energy for cells. Mutations in these IDH genes leads to several types of cancers, including AML and solid tumor cancers.

In preclinical studies, AG-120 successfully blocked the abnormal function of mutated IDH1 and led to the death of leukemia cells. AG-120 is also currently being studied in a Phase 1 trial in patients with advanced solid tumors having an IDH1 mutation. Agios expects to present the results from this study in 2015.

AML is the most common type of leukemia in adults, and only 20-25 percent of patients survive up to five years. Most AML patients are not eligible for bone marrow transplants and do not respond to chemotherapy. About 15-20 percent of AML patients carry an IDH1 mutation, amounting to about 3,500 cases of IDH1 mutation-AML every year.