Amgen is preparing to make an unusual argument to an FDA advisory panel tomorrow. The world’s largest biotech company (NASDAQ: AMGN), with research operations in Seattle and Cambridge, MA, plans to make a case that one of its drugs should be used by just a subgroup of patients with colorectal cancer who appear to be most likely to benefit from it.
Normally, drugmakers spend a lot of time and money trying to prove their products should be used by the broadest number of patients possible. This meeting will be closely watched by hundreds of cancer drugmakers, since it could be an important test case for the movement toward creating more personalized cancer medicines.
The hearing will focus on two colorectal cancer drugs that hit the same target that’s a culprit in tumor proliferation, EGFR. The medicines, Amgen’s panitumumab (Vectibix) and Eli Lilly’s cetuximab (Erbitux), have both been shown in backward-looking statistical analyses to work much better for about 40 percent patients with a normal form of a gene called KRAS. If you’re one of the unlucky others with a mutant form of KRAS, which makes cancer more aggressive, the drugs won’t work. Since these treatments are hugely expensive, at $10,000 a month for the Lilly product and $8,000 a month for the Amgen version, there’s a societal interest in genetic testing of these patients before they get treatment. It also could spare a whole lot of people the nasty skin rash and other side effects that come with the drugs, if they have little chance of benefit.
“Amgen has concluded that the benefit/risk profile of panitumumab will be improved by restricting monotherapy use to those patients whose tumors have the wild-type (normal) KRAS gene,” the company said Friday in briefing document posted online.
I’m always skeptical when drug companies say they are eager to narrow down their potential pool of customers, but in Amgen’s case there is a back story of business and science that explains how it arrived at this position.
For starters, the Lilly product got to the market first in February 2004, when it was developed by ImClone Systems. The drug has built a commanding lead in market share, with $1.3 billion in sales last year.
Amgen paid a fortune-$2.2 billion-in 2006 to acquire Fremont, CA-based Abgenix to get full control over the second-in-class contender, panitumumab. But the drug has not emerged as the kind of $2 billion-a-year commercial success originally predicted by analysts. That’s partly because a study in March 2007 was halted when it showed the Amgen drug raised the risk of death in a clinical trial when used in tandem with Genentech’s bevacizumab (Avastin), another colorectal cancer drug that works differently.
That result wrecked Amgen’s marketing strategy, which had been to position panitumumab as a potentially safer, and lower-cost, alternative. The Amgen drug is made of fully human DNA copies. That’s different than the part-mouse, part-human antibodies in the Lilly product, which are thought to be capable of sparking more of an immune-system reaction against the drug.
Not surprisingly, the safety concern has made it hard for Amgen to gin up sales for this product, which had $170 million in sales last year. But instead of letting the Amgen drug fade into a treatment of last resort, the company went back to what it learned from tumor samples collected from earlier trials, as I described in this story back in August. When the company filtered patients based on whether they had a normal KRAS gene, or a mutated form, they found a striking result.
About 17 percent of patients with normal KRAS genes had tumors shrink after they took the drug, while none of those with mutated KRAS genes saw that benefit, according to research published in March in the Journal of Clinical Oncology.
Amgen thinks that result may point to a way to salvage the commercial potential of this drug. Patients in the niche may be more motivated to take the drug if they can see it has a higher likelihood of working. Amgen has compared this situation to Genentech’s success with trastuzumab (Herceptin), a drug that’s approved only for about one-fourth of breast cancer patients with a mutated form of the HER2 gene. Even without selling the drug to all breast cancer patients, Genentech was able to generate $1.3 billion in U.S. sales last year.
The FDA has made it clear it wants to encourage more drugmakers to do this kind of precise whittling of patient populations, to boost the likelihood of success. The part officials don’t like is that few companies plan ahead to do this kind of analysis. Rather, they decide to shoot for the largest patient population in clinical trials, and then try to do statistically dubious “data dredging” after a trial is completed to fish around for some positive sign in a subgroup.
“An ideal scenario is one in which the relationship of the biomarker to potential action of
the drug is recognized very early—indeed, such a relationship might be the motivation
for starting the drug’s development,” the FDA said in its briefing document in advance of the panel.
Both Amgen and Lilly say they want to be able to include new data in their drugs’ prescribing information, so they can legally promote the benefits of the drugs for patients with normal KRAS status. If they get their way with the drug label, and time shows that this strategy expands sales rather than limits them, then you might well see other companies starting to get with the program of more personalized medicine.