how much longer they last, and how many patients relapse into active disease.
“Hopefully this is a treatment that will last for years and years, but that will always remain an open question,” Stein says.
But the expressway is open to Agios if the data hold up. The FDA has granted a fast-track designation for AG-221, which would speed the agency’s review of the drug once it has completed a pivotal trial.
AG-221 targets an enzyme called isocitrate dehydrogenase-2 (IDH2). That enzyme helps generate energy within cells, but when it’s mutated in cancer, it creates a byproduct that flips a genetic switch in immature bone marrow cells. Those cells then don’t develop properly, and start multiplying wildly, rather than becoming the blood cells they were supposed to become.
By binding to mutated IDH2, AG-221 is supposed to block the byproduct and allow bone marrow cells to mature normally. As such, it works very differently than chemotherapy, which kills cancer and healthy cells alike.
If it works, it would represent a paradigm shift in the treatment of AML—a fast-moving blood cancer whose only cure is a bone marrow transplant that is only available to a small number of patients. Between 9 and 13 percent of patients with AML have the IDH2 mutation.
Here’s a rundown of the data Agios is reporting today. The company enrolled 73 patients in its study, but 28 couldn’t be evaluated because they became too sick or their disease was too advanced.
“These patients are so ill that it is difficult to evaluate them before they’ve gotten a month of therapy,” Stein says.
Of the 45 evaluable patients:
—Six responders have no trace of cancer in their system (complete remissions).
—Nine responders have no trace of leukemia, but their blood levels haven’t returned to normal yet.
—None of the six with a complete remission have relapsed.
—Ten responders had partial remissions, meaning some of their leukemia is gone.
—90 percent of the responders have been on therapy for at least three months; four responders have been on AG-221 for at least six months, with some on treatment as long as seven or eight months, according to Stein.
—Ten patients have stable disease; Stein says that for many of these patients, the number of “blasts,”—abnormal, immature cells that are a hallmark of leukemia—in their blood have decreased. Their platelet counts, however, haven’t returned to normal.
AG-221 is part of Agios’s partnership with Summit, NJ-based Celgene (NASDAQ: [[ticker:CELG]]). Celgene holds worldwide rights to the drug, and is paying all of its development costs; Agios would get milestones and royalties on the drug if it continues forward. Agios does hold U.S. rights to AG-120, however, and full rights to a third drug, AG-348, for an inherited form of anemia known as pyruvate kinase deficiency. Agios will be reporting data from the first study of AG-348 at ASH as well.
Separately, while Agios looks to start a registrational trial in AML, South San Francisco, CA-based Sunesis Pharmaceuticals {NASDAQ: [[ticker:SNSS]]) recently finished one with its drug voxarosin. The trial’s lead investigator is presenting the data at ASH today, as well. Although the trial didn’t meet its primary endpoint of extending the lives of patients with relapsed or refractory disease, subgroups of patients in the trial saw greater benefit. Sunesis plans to ask regulators in the U.S. and E.U. for approval.
