Not surprisingly, the recall is killing Affymax (AFFY) stock, since the drugmaker was hoping to penetrate a huge market dominated by billion-dollar-sellers such as Epogen and Aranesp, which are sold by Amgen (AMGN), as well as Procrit, which is marketed by Johnson & Johnson (JNJ). Given that Omontys is the only drug that Affymax currently sells, its shares plunged about 85 percent in pre-market trading this morning and, as of 11 am EST, have yet to recover.
However, a conference call this morning is unlikely to assuage investor pain, at least those who were not shorting the stock. The Affymax team noted that serious hypersensitivity occurred with intravenous administration about 3 minutes after a first dose, suggesting long-term use may not be an issue. But they have been unable to prospectively determine which patients may have such a reaction. So far, by the way, about 25,000 people have been given Omontys.
So far, actual usage has yielded a hypersensitivity rate of .2 percent with about one-third of patients considered serious; the fatality rate was .02 following a first dose. This translates into 50 serious hypersensitivity reactions and five deaths, although two have been described as related to cardiovascular issues. At the clinical trial experience was different - the rate of hypersensitivity was similiar, but not the level of serious reactions. There were 4,000 patients in Phase III testing.
Could manufacturing be an issue? This remains unclear, although there were single dose units made during the clinical trial phase and multi-dose units once commercial marketing began. And no specific lot has been singled out as potentially problematic. Consequently, no cause has been determined for the serious and, sometimes, fatal reactions, and it is unclear which patients may be at highest risk.
"While this overall adverse event rate is within the label and it's well-known (this class of drugs) isn't risk-free, looking at FDA's advere event database for Epogen, Omontys appears to confer a 100-fold higher incidence of hypersensitivity and an 8.5-fold higher incidence of drug-related death (and that's new). This analysis isn't perfect, but we think the magnitude is such that there's a clear signal here," writes RW Baird analyst Christopher Raymond, in a research note. "... While we applaud Affymax's move, assuming there is a workable re-launch plan, we see a much longer road to regain the faith of the nephrology community."
Another, more significant issue is the extent to which this episode may cause the FDA to become more cautious about approving such biosimilars. Although Omontys is not considered a biosimilar - the Affymax treatment is a different molecule than Epogen or Aranesp - the medicine is still similar to these other biologics, suggesting the agency may see a need to hesitate before approving biosimilars.
[UPDATE: "Safety issues with Affymax’s Omontys shifts focus to complexities associated with manufacturing complex biotech drugs," writes Deutsche Bank biotech analyst Robyn Karnauskas in an investor note. "In our opinion, such events cause a fair amount of skepticism regarding safety of biosimilars. We take European pure red cell aplasia issued with Eprex as example which caused some apprehension among physicians regarding safety of follow on biologics." Eprex is sold by J&J in Europe. "PRCA was associated with one specific formulation of Epo - Eprex. These events were only seen in the EU but generally made physicians skeptical about the use of follow on biologics."]
[AND HERE IS ANOTHER UPDATE: "Remember, that by 'piggy-backing off of some of the innovator’s data, some bio-similars might launch with less data than AFFY had generated. To me, this is another case study that suggests bio-similar launches will – in general – be slow. Doctors will (or at least should) wait for proper real-world exposure data before prescribing," writes ISI Group biotech analyst Mark Schoenebaum in an investor note.
"There is just no other reliable way to detect very rare adverse events. However, this does NOT mean that some bio-similars will not be eventually used. This situation also highlights why quality and relevant biologics experience are critical to the development of truly safe bio-similars – thus, it may be that the traditional 'branded' biologics companies end up dominating the bio-similars market as well."]
quesitonmark pic thx to purpleslog on flickr