eliminate the need for transplants. But, Stein cautions, “I think that it’s way premature to say that’s what’s going to happen.”
Indeed, much is left to be proven. Here’s more on what the study has shown so far:
Agios enrolled 22 patients who have either AML or myelodysplastic syndrome (when the bone marrow doesn’t produce enough healthy blood cells) and an IDH2 mutation, and have failed one to four prior rounds of chemotherapy—very sick patients. These patients, who have a median age of 62.5, are receiving 30 mg, 50 mg, or 75 mg of AG-221, in pill form, twice a day, or a 100 mg dose once a day, for 28 days.
The data being presented today are on seven patients who were on 30 mg or 50 mg doses of AG-221. (Three additional patients were in the 30 mg group, but died of disease-related infections and couldn’t complete a full cycle of treatment.)
Six of the seven patients responded to the drug, meaning their 2HG levels decreased by more than 90 percent, according to Agios. Three of them saw their cancer completely wiped out. Two others had a complete remission as well, but their platelet counts haven’t returned to normal levels yet (Stein says investigators are hoping with further treatment they’ll get to that point). A sixth patient had a partial response to the drug.
Stein says that the one person who didn’t respond to the drug, who was on a 50 mg dose, is being evaluated to find out what was different.
“It may have something to do with other gene mutations the patient had that may be driving their leukemia,” he says.
So what about side effects? While Agios said the drug has been well tolerated so far, there were two potential issues. One patient developed differentiation syndrome—a complication in which fluid leaks into the lungs and other tissues. While that condition can be dangerous, Stein says it’s easily treated with steroids. Nonetheless: “That’s something we’re going to have to keep a very close eye on,” he says.
A second patient developed confusion, though Stein says the patient who had it was “critically ill” and it’s unclear whether it was related to the drug, and that no other patients in the study have experience such episodes.
Agios has already begun testing the 75 mg and 100 mg doses of AG-221. They haven’t had any safety problems or dose-limiting toxicities, but the company doesn’t have the efficacy data on those patients yet, according to Stein.
Agios still hasn’t chosen which dose to study in its next trial. Once it does, Stein says the company will expand its current study, treat a few more patients at that dose, sit down and look at all the data, and decide what the best clinical path forward is.
Though uncertainties still abound, today’s presentation marks an important milestone for Agios, which was launched in 2007 by Arch Venture Partners and Flagship Ventures. Third Rock Ventures joined Arch and Flagship to lead a $33 million Series A for Agios the next year. The VC firms then hired Schenkein, the former head of cancer drug development at Genentech, to steer the ship.
Schenkein took over with big dreams for Agios. “What I saw was the potential to move into a novel area of targets that could [hit] cancer from an orthogonal approach that we had just not been doing,” he told me last year. “It had the feel of ‘go big or go home.’”
And indeed, a lot is riding on AG-221. While Summit, NJ-based Celgene (NASDAQ: [[ticker:CELG]]) holds worldwide rights to the drug under a $130 million deal the two companies struck in 2009, and would thus gain the most financially from its success, Agios will earn milestone payments and royalties should it continue forward. But more importantly, the drug is a test case for Agios’s approach of going after cellular metabolism targets. A second drug, AG-120—which Agios owns U.S. rights to—is designed to work very similarly to AG-221, for instance. Agios is developing AG-120 as a treatment for solid tumors with the IDH1 mutation. And the company is looking into a class of diseases known as inborn errors of metabolism after that.
Agios raised over $120 million in equity financing and another $141.2 million in partnership revenue before its IPO in July. It added another $111 million in net proceeds from the offering, and ended 2013 with about $194 million in cash on hand.
