The announcement last night that Affymax (NASDAQ: AFFY) is recalling all lots of its red blood cell stimulating medicine Omontys could have broader implications for how the Food and Drug Administration (FDA) evaluates similar drugs going forward.

Omontys was recalled following some fatal, severe allergic (anaphylactic) reactions that occurred within 30 minutes of receiving the first dose. Unless the problem can be traced to an obvious additive in the product or some characteristic in affected patients that made them susceptible to the reactions (enabling doctors to avoid dosing high risk patients) then quick re-introduction of the drug could be challenging.

In a statement, FDA said that there were 19 anaphylactic reaction reports. Three of these reactions resulted in death. Others required prompt medical intervention and resuscitation. Some required hospitalization.  Omontys is used to treat anemia in kidney dialysis patients. It was supposed to compete directly with Amgen’s older and much more widely used drugs Epogen and Aranesp.

The episode could have broader implications for how FDA looks at biologics more generally, and especially other follow on products aimed at stimulating production of red blood cells. There is an inherent unpredictability in biologics owing to our inability to fully characterize these drugs. This truth is being borne in the relative caution that FDA has shown in fully implementing a pathway for the approval of “biosimilars” – follow on or generic versions of existing biologics. It will also affect how FDA views “bio betters” — new versions of existing drugs that are believed to have superior qualities that enhance the new drug’s safety or effectiveness.

This latest episode is likely to heighten FDA’s caution still more.

While Omontys was a different molecule than either Epogen or Aransep (and a fairly simple molecule) there could be some subtle, long-term lessons for FDA. The agency has years of experience with biological agents that simulate red blood cell production, and the inability to ferret out the risks with Omontys is likely to underscore how hard this science remains. Our tools for identifying both small and more significant differences between otherwise similar-acting biologics, and then translating when these changes can have clinical implications, are still an evolving science.

When these arguments were made during the debate over creating a biosimilars pathway, they were often dismissed. They were characterized as the self-interested pleadings of those trying to protect existing franchises. Perhaps there was some hyperbole on both sides of that debate. But the fact is, the science of biosimilar agents is still evolving. Regulatory constructs are likely to further reflect that evolving uncertainty.

For these reasons, FDA has already shown caution in approving “biosimilar” drugs and — in particular — defining a pathway for these medicines that gives sponsors a sufficiently easier route to the market than the one enjoyed by the innovator drug they are copying. This has created some uncertainty among sponsors whether the biosimilar pathway is really worth pursuing in certain cases, or would they be better off filing applications for new biologics (and securing the benefits that such a new Biologics License Application affords).

That environment of caution is likely to mount. It will blunt at least some of the economic rewards that policymakers envisioned when they created the biosimilars pathway.
The fact that the biosimilars don’t typically offer any clinical advantage (only potentially economic advantages) over their branded complements is likely to only increase the regulatory skittishness. The potential for risk needs to be weighed against the bounded public health benefits that these follow on products offer.

Episodes like these might also give added caution to physicians. Biologics that are seemingly similar in their structure and action can nonetheless have different profiles with important implications. Physicians could have additional pause about using the follow on drugs. All of these facts may weigh on the biosimilars enterprise.

As for FDA, it might well take a harder view that the safety of biosimiliars needs to be even more firmly established before approval. The same could apply to bio-better drugs that try and use new molecular scaffolding to achieve the same ends as existing biological drugs (especially tweaked versions that don’t offer distinct clinical advantages over the older medicines).

The situation involving Omontys is still unfolding, and many questions remain. But it is through episodes like these that FDA has often shaped some of its most cautionary principles.