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for normal KRAS patients, but it struggled to persuade the FDA. That’s because the company used a retrospective analysis, which looks backward in time for clues on who benefitted from Vectibix and who didn’t. It’s a common tactic, but statistically, it’s like throwing darts at a board, walking up to the dartboard with a magic marker, drawing a circle around where a dart hit, and declaring you hit the bulls-eye. Not valid, in other words.
The study Amgen announced last week was from a more rigorous challenge—a prospective study. Once Amgen had a strong hypothesis that KRAS was important for Vectibix, it modified the design of the 1,100 patient trial to ask that question in advance—whether the drug really works better for normal KRAS patients. That’s more like stepping behind the line, declaring you’ll throw a dart at the bulls-eye, and then actually hitting it. That’s the kind of evidence the FDA prefers.
Amgen isn’t providing any details yet on the magnitude of benefit for normal KRAS patients, compared with everybody else, but the findings will be presented at an upcoming medical meeting, Reese says. Presumably, this would lead to another update of the drug’s prescribing information, although Reese wouldn’t comment on talks with the FDA. But there’s clearly room for improvement in the drug label. It currently says Vectibix has demonstrated effectiveness in patients getting their third-line of therapy, after two other courses failed. The latest trial is from a potentially bigger patient population—those getting their first course of treatment after they’ve been diagnosed.
And this being Amgen, with the deep pockets it has, the company isn’t done yet with the KRAS question. It has still one more trial ongoing to test this hypothesis, in colon cancer patients getting their second-line therapy. That trial, with another 1,100 patients, is expected to produce results next month, Reese says.
So far, Amgen hasn’t seen any evidence yet, from its five year-long biomarker discovery effort, that KRAS is the key biomarker to predicting success for other cancer drugs used in different patient populations. The company is using sophisticated equipment that can look for things as tiny as single chemical variations in DNA, known as SNPs, that might offer predictive clues of which patients will respond to a therapy, says Scott Patterson, Amgen’s executive director of medical sciences.
“We believe our KRAS experience with Vectibix is a model, and it reinforces our commitment to biomarkers early in the drug development process,” Patterson says.
I asked for specific examples of other biomarkers that appear to help predict which patients will respond to other Amgen drugs that are still experimental, but Patterson didn’t want to name any names. Speaking broadly, he says the hope is that these biomarkers will have a solid scientific rationale by the middle stage of clinical trials. That’s when they can serve as a prospective guide to increase the company’s success rate in Phase III clinical trials, where it has to spend the really big bucks, like in the Vectibix first-line study.
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