EPO and Aranesp

Few drugs have had the sustained attention from the drug safety community given to EPO and its derivatives. Oral contraceptives, anti-psychotics, perhaps NSAIDS are the only rivals in this regard. EPO's safety concerns began with its launch, when the issue of what would happen if the drug were overused in patients with marginal endogenous production of the substance was raised. Then, there was the pure red cell aplasia episode in Europe. That EPO was involved in the outbreak everyone accepts. Exactly how it occurred is still a bone of contention among some. Now we have safety concerns occurring with Aranesp.

EPO has been a phenomenally successful franchise for Amgen and J&J. For the former, it has been at the core of the company's ascent into the rarified air of multi-billion dollar in capitalization pharmaceutical companies. So successful has Amgen become that the city fathers in Thousand Oaks have supposedly told the company to expand elsewhere. Which it is doing, in South San Francisco, about 400 miles up the road in the international hub of the biotech industry and in the shadows of its rival, Genentech.

This all brings us to Aranesp, a second-generation EPO. Trying to develop its EPO franchise further with expanded indications for Aranesp, Amgen set up a trial with Aranesp to show that increasing hematocrit would lead to more oxygen deliver to tumor cells in head and neck cancer cases. The increased amount of oxygen would lead to the production of more free radicals during the radiation therapy at the core of treating such cancers. The unexpected result of the trial, though, was just the opposite of what was expected, and it resulted in some pundits suggesting Aranesp helped the tumor thrive and survive. No one questioned the safety of Aranesp in its labeled indication. Just this new area. However, since the drug is used in oncology, the risk of a safety problem in a key therapeutic area was no doubt troubling to Amgen. It was certainly troubling to investors. Everyone became concerned with every trial result for this drug.

Recently, one such trial came to conclusion without any indication of a safety problem. Investors (and analysts) sighed in relief. Except the trial really doesn't address anything but the crudest of questions, since the trial isn't really large enough (and wasn't designed to be large enough) to determine if there is a safety problem with the drug. What we do know is no registry data have yet been released indicating whether there's a problem. Nor have any trials an order of magnitude larger than those recently reported on been undertaken to demonstrate the product's safety. (It seems unlikely such a trial will be mounted any time soon.) What we also know is that there's lots of questions, but little clear evidence of a problem. Which isn't to say a problem doesn't exist.

Absence of evidence isn't the same thing as evidence of absence. Never has been, never will be.