SAN FRANCISCO (TheStreet) -- Agios Pharmaceuticals (AGIO) and partner Celgene (CELG) will start pivotal studies of their cancer metabolism pill AG-221 in 2015 designed to support worldwide approvals, the companies announced Sunday.
Updated results from an early-stage study of AG-221 continue to show strong and durable clinical activity. More than half of the patients with advanced blood cancers are responding to treatment with AG-221, including some responses lasting as long as eight months. One-third of patients in the study achieved a complete remission or a near-complete remission following treatment with AG-221. Researchers see two deaths in the trial possibly related to AG-221.
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A presentation of the AG-221 phase I study data is scheduled for later today at the American Society of Hematology annual meeting underway here.
Agios and Celgene are able to move quickly from a phase I study directly into studies designed for regulatory approval because AG-221, a pill taken once or twice per day, targets a specific genetic mutation found in some cancer cells. By identifying and enrolling only those patients with tumors expressing this mutation into its studies, response rates to AG-221 are significantly better than what's normally seen with traditional chemotherapy.
Agios developed AG-221 and has shepherded the drug through early clinical development. Celgene licensed worldwide rights to AG-221 from Agios in June 2014.
The "global registration program" for AG-221 will begin in 2015, but Agios and Celgene are not providing details on the studies or a more exact timeline.
In this latest update to the phase I study, 73 patients with advanced blood cancers, mostly acute myeloid leukemia no longer responding to current medicines, have been enrolled and treated with escalating doses of AG-221. All the patients have tumors containing a mutated, metabolic enzyme known as IDH2. Normally, cells use IDH2 to help break down nutrients and generate energy. When mutated, IDH2 alters the genetic programming of cells, preventing them from maturing and causing them to grow uncontrollably.
Patients with AML have bone marrow crowded with undifferentiated, rapidly dividing blast cells. AG-221 blocks the mutated IDH2 enzyme and allows the leukemic cells in the bone marrow to mature into normal blood cells.
Agios estimates that between 18-24% of AML patients harbor the IDH2 mutations or a similar IDH1 mutation.
Of the 73 enrolled patients, 45 patients were evaluable for the efficacy analysis presented at the ASH meeting. The results showed that 25 of the 45 patients achieved a tumor shrinkage response to AG-221, for an overall response rate of 56%.
Of the 25 responding patients, six, or 13%, achieved complete remission, meaning there was no evidence of leukemic cells in their bone marrow. Another five patients showed near-complete remissions. Ten patients had partial remissions following AG-221 treatment.
None of the patients with complete remissions have suffered a relapse to date. Ninety percent of the responses to AG-221 have lasted at least three months, with the longest response now out to eight months.
As stated, the updated efficacy analysis includes only 45 of the 73 patients enrolled in the phase I study to date. Twelve other patients started treatment too recently to be included in the analysis. Another 16 patients started treatment with AG-221 but discontinued from the study within one month, which prevented them from being assessed for efficacy.
The patients enrolled in phase I study had very advanced cancer without current treatment options, so it was expected that some would be too sick to be helped even by a targeted drug like AG-221. But if the 16 discontinued patients were counted in the efficacy analysis, as they would be in a study designed for approval, the overall response rate to AG-221 would be 41% and not 56%, as stated by Agios and Celgene.
All 73 patients enrolled to date were assessed for safety. There have been 11 patient deaths reported in the study to date, with two deaths deemed possibly related to AG-221 by study investigators. One of these patients died with sepsis and hypoxia, the other had atrial flutter.
The majority of serious adverse events reported in the study were due to the cancer. Thirteen patients reported serious adverse events possibly related to AG-221, including nausea, diarrhea and fatigue.
The phase I study continues to enroll additional patients and higher doses of AG-221 are being used.
Agio is developing a second drug known as AG-120 which works by blocking a related, mutated enzyme known as IDH1. Updated results from early study of AG-120 in advanced blood cancers was presented last month.
Also today, Agios and Celgene said pivotal studies designed to get AG-120 approved worldwide would begin in 2016. Celgene owns rights to AG-120 outside the U.S., while Agios maintains full rights to the drug here.
Both AG-221 and AG-120 are being studied in patients with solid tumors. The first results from these studies are expected next year.