Late yesterday, the FDA disclosed that Affymax and its marketing partner, Takeda Pharmaceuticals, issued a so-called voluntary recall of their Omontys medication, which is used to treat anemia in adult dialysis patients, after there were 19 reports of anaphylaxis, a serious and life-threatening allergic, at dialysis centers in the US. Three of the cases ended in death and several other patients required hospitalization (
here is the FDA statement).
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
19 Comments
Is this your narrow opinion? It's quite a stretch.
Thanks, as always, for your friendly notes. I surmised this may be the case simply because the FDA has been quite conservative about biosimilars. Is this a stretch? This is certainly a legitimate concern and, therefore, a conversation worth having.
Coincidentally, after you left your comment, a biotech analyst distributed an investor note in which she expressed the same concern. And so I've added her remark at the bottom of the story. This does not mean to suggest this is the correct way to view the matter, but again, it is worth considering given events.
Hope this helps, ed
It is still a stretch IMO.
You make a good point and I don't disagree with your notion. As yet another analyst points out, however, some biosimilars will launch with less data than was avialable for the Affymax drug, and will be relying on data from the innovator. This is simply another way of looking at the issue. Please see the latest update to the story.
As to your identity, I recall you started commenting here with your moniker not long after i ran an interview with an industry ocnsultant named Ramsey Baghdadi. A coincidence? Shrug. But this explains my reference. With all due respect, I'm not much interested in your height or weight.
Anyway, thanks for the conversation.
Regards ed
Who knows, people might start to take you seriously.
http://www.thedailybeast.com/newsweek/2012/09/09/the-nazis-and-thalidomide-the-worst-drug-scandal-of-all-time.html
The Japanese did same experiment to Chinese during the Japanese invasion to China from 1937 to 1945. It was called "731 bacteria Army". All the doctors who worked in "731 Army" were later captured by Russia Red Army, and were sentenced in Russia.
The other similarity between Takeda and Grunenthal was that Takeda Japan also paid doctors to keep silence and not to report Actos bladder cancer to Japanese government in last 15 years.
John, the background rate of bladder cancer in the US population is 20/100,000 patient years. Multiple case control studies have estimated the RR of bladder cancer for patients on Actos at 1.2 to 2.0. So a realistic estimate of the bladder cancer cases attributable to Actos is about 1 per 10,000 patient years, or 0.01% per year.
You really think they picked right up on an AE with incidence of 0.01% and starting paying doctors off to cover it up?
Based on peak sales of about $3B per year, an annual price of therapy of about $2000, one can calculate that the peak number of patients on drug was about 1.5M. Multiply that by 0.01% and you have 150 cases of bladder cancer a year.
Its going to be hard to get to 30,000 bladder cancer cases unless you assume that the average patient took the drug for 200 years.
Maybe its time to move on to aliens or the trilateral commission.
Civilized infrastructure (water treatment, housing for livestock away from human homes, clean city streets of garbage, get rid of rat infestations, etc.) is the best way to control typhus.
So many people were sickened after the infrastructure was ruined during the two major wars in Europe and Asia that there was no need to infect people for experimentation, was there?
Of course, Takeda would never admitted the fact that Actos had caused bladder cancer. It just like Grunenthal denied the fact to their own employee whose wife was on Thalidomide and gave birth to a baby without ears.
John2, your calculation was wrong. 1,500,000 x 0.01% is 15,000 cases a year. This annually increased number of bladder cancer well explains the bladder cancer data reported by American Cancer Society. According to the cancer data in US, the bladder cancer in male was declining, and the bladder cancer in female was stable before year 2000. After year 2000, the bladder cancer rate increased at 5,000 to 6,000 each every year; by 2010, the bladder cancer in both male and female increase 17,500 comparing to the 60,000/year before 2000.
The annual sales of Actos over 3 billion started in 2006 and continue to rise to the first half of 2011 with average sales with peak at 4 billions. According to your rate, this could develop 15,000 to 20,000 bladder cancer each every year. This well explains why the bladder cancer has been steady increase after year 2000, because Actos was approved in second half of 1999.
The incident rate of 73,510 reflected the 2 years of latency from the peak sales of 2010.
The incident rate of 73,510 reflected the 2 years of latency from the peak sales of 2010. The American Cancer Society stated from 1982 to 1999, the bladder cancer in male had been declining, and in female had been stable. Why these bladder cancer incease followed the sales increase of Actos? Does this have to do with the while male and their life style? The white male has been around in this country for 300 years and they didn't have increased bladder cancer year over year until Actos had been marketed after 1999.