Organon Concealed Bleeding Data For Arixtra
3 CommentsBy Ed Silverman // April 24th, 2008 // 1:31 pm
The drugmaker that was recently purchased by Schering-Plough had a very unimpressive track record of disclosing side effects to the FDA, according to FDA and court documents. Last week, you may recall we wrote Organon faces allegations that the number and severity of serious adverse events associated with its withdrawn Raplon neuromuscular drug weren’t disclosed before or after FDA approval.
As it turns out, Organon also allegedly diluted data in an NDA submission showing excessive bleeding caused by the Arixtra blood thinner before it was approved in December 2001. Both the Arixtra and Raplon episodes, by the way, took place while Schering-Plough’s senior vp for global fertility, Hans Vemer, headed Organon. He went to work for Schering-Plough four years ago and, until recently, was senior vp of global medical affairs.
The Arixtra matter occurred as part of the New Drug Application submission to the FDA in February 2001. To support its application, Organon and its marketing partner, Sanofi, referenced four pivotal studies detailing various doses of Arixtra compared with another drug, Lovenox, in knee and hip joint surgeries in the US and Europe. But only two safety tables existed for the four studies.
The FDA reviewer caught the problem and wrote there was a “deletion” of a table for the hemorrhage section of the labeling. This is “unacceptable,” the reviewer wrote. “This safety information is important to the physician.” Actually, there should have been a separate table to accompany each study. By combining four tables into two, Organon effectively blended 11 instances of major bleeding - compared with just one for Lovenox - in one of the four trials, which was published in the New England Journal of Medicine at nearly the same time the review was being conducted. (Please click on ‘Read More’ to see the two tables that were submitted).
Sometimes, timing is everything. Arixtra, we should point out, is now marketed by Glaxo.
MD 1
It appears that Organon had some major skeletons in its’ closet when Schering-Plough purchased them, with the biggest skeleton already working at their company. This is the second item within a week. Perhaps SP may geta snese of how Pfizer felt after they bought Pharmacia and got caught up in all the Human growth Hormone problems? What is trult puzzling is why SP wouldn’t have been aware of some of these things given that they had the former US head of Organon already on their payroll. This seems to be a very blatant oversight regarding the most important problematic side effect, bleeding, with Factor Xa Inhibitors. I wonder how many patients have received this product and had bleeding as a side effect. Compare that with how many would have bled if they had received enoxaparin instead. It appears to be not much benefit with a lot of risk.
As a physician, I despise when these companies are not forthcoming with the whole story. I’m just finding this out several years later! Outrageous!!
Brittany
Arixtra showed decreased bleeding compared to Lovenox in the acute coronary syndromes trial, OASIS 5.
MD2
In response to the comment where Brittany noted that Arixtra showed less bleeding compared to Lovenox in the ACS trial, OASIS 5: There was a statistically significant amount of heparin and Lovenox crossover in that study versus Arixtra and heparin. GlaxoSmithKline should have learned from SYNERGY (Lovenox versus heparin) that you must NEVER mix agents as they did to a large amount in the OASIS trial. Lovenox remains the safest and most efficacious antithrombotic agent on the market for ACS and any other indication.