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separately by the FDA. If future trials prove the theory that the drugs will work better together than they would as solo therapies, the companies intend to jointly file for FDA approval of the combination—a strategy that’s never been tried with two novel drugs, Gilliland says. “We’re having ongoing discussions with the FDA and they have been supportive,” he says. “They understand that in cancer you have to use combinations, because they improve efficacy and they help prevent resistance.”
Gilliland predicts that the strategy of partnering very early in the development process will catch on in the pharmaceutical industry. “We shouldn’t all be making the same drugs—we should be talking to potential partners,” he says. “Our argument is if you show synergy with a combination you should run with that, rather than putting patients on single therapies that are not likely to be successful.”
As for identifying patients who are most likely to respond to particular drugs, a group of researchers will be presenting a study on Tuesday that Gilliland says demonstrates Merck’s commitment to that strategy. The study involves ridaforolimus, a drug that inhibits an enzyme called mTor and that Merck is developing with Cambridge, MA-based Ariad Pharmaceuticals (NASDAQ: ARIA). The drug has hit some bumps, most recently on March 12, when an advisory panel to the FDA voted 13-to-1 against the approval of ridaforolimus for patients with some bone cancers. The FDA is expected to hand down its decision by June 5.
In the study being presented at ASCO, ridaforolimus was tested in patients with non-small cell lung cancer who have a specific genetic mutation called KRAS. The study shows that patients with the mutation who were put on the drug experienced significantly longer “progression-free survival”—the period of time during which their tumors did not grow—than did those who were given a placebo. “We don’t know yet if it will translate to overall survival, and it’s a small study, but it’s a big signal,” Gilliland says. “So we’re very excited about the opportunity for bringing it forward into a broader confirmatory trial in lung cancer.”
Gilliland says identifying patients most likely to respond positively to cancer therapies will alleviate a rampant problem in the pharmaceutical industry: drugs that fail in late-stage trials, after companies have spent several years and millions of dollars trying to prove they work. “Since 2010, there have been 16 [late-stage] failures in oncology across the industry,” he says. One of those involved Merck’s lymphoma drug vorinostat (Zolinza), which the company hoped to have approved to treat mesothelioma. But the trial failed last September. “We didn’t have a clear idea of what the [drug] might be doing to the cells,” Gilliland admits.
Now, says Gilliland, Merck is much more vigilant in early trials about choosing the right patients to test, and giving up quickly if they don’t respond as well as predicted. “The insight we’ve gained collectively with these failures is you have to understand what subset of patients is gong to respond to your drug and you have to have the biomarkers to enable that,” he says. “If we’re going to fail, we try to fail early with as few patients as possible.”
He hopes Merck’s high-profile presence at ASCO will show the company is following that mantra. “We’re looking for a very high degree of efficacy, and if we don’t see what we’re looking for, we stop,” he says. “We’ve set a high bar for futility.”