In the New York Times story by Andrew Pollack on February 24, both Dan Coyne and I are interviewed about the peginesatide (Omontys) recall. The question that we left hanging is whether peginesatide will gain FDA approval and reintroduced. I have my doubts. Here is why.
The reason that these fatal reactions were detected was that the FDA has a sound pharmacovigilance mechanism in place. After a drug is launched commercially tens of thousands of more patients are exposed to the drug than could ever be studied. A rare reaction occurring 2 per 1000 patients may not be detected on the basis of chance alone in a study (Emerald 1 and 2 had 693 and 725 patients enrolled), whereas when the drug is used in 25,000 patients is more likely to be detected.
Using this same argument, to demonstrate that patients are safe from such a reaction would require a study in tens of thousands of patients. Something that would be extraordinarily difficult and expensive. Peginesatide already has one hit against it - it is only approved for use in dialysis patients, because in the non-dialysis CKD patient population a safety signal was detected (see NEJM papers published January 24 2013 : link 1 and 2).
In other words, the most likely scenario is that even if the company finds that the reason for the reactions is an impurity resulting from the manufacturing process, it will be years and perhaps never, for us to see the re-introduction of peginesatide. Frankly, it's dissapointing because with peginestaide's introduction many had thought that the ESA price would fall and that would be good for health care costs. It could also spell the death knell for Affymax, which at least for now had been a one-product wonder.
The reason that these fatal reactions were detected was that the FDA has a sound pharmacovigilance mechanism in place. After a drug is launched commercially tens of thousands of more patients are exposed to the drug than could ever be studied. A rare reaction occurring 2 per 1000 patients may not be detected on the basis of chance alone in a study (Emerald 1 and 2 had 693 and 725 patients enrolled), whereas when the drug is used in 25,000 patients is more likely to be detected.
Using this same argument, to demonstrate that patients are safe from such a reaction would require a study in tens of thousands of patients. Something that would be extraordinarily difficult and expensive. Peginesatide already has one hit against it - it is only approved for use in dialysis patients, because in the non-dialysis CKD patient population a safety signal was detected (see NEJM papers published January 24 2013 : link 1 and 2).
In other words, the most likely scenario is that even if the company finds that the reason for the reactions is an impurity resulting from the manufacturing process, it will be years and perhaps never, for us to see the re-introduction of peginesatide. Frankly, it's dissapointing because with peginestaide's introduction many had thought that the ESA price would fall and that would be good for health care costs. It could also spell the death knell for Affymax, which at least for now had been a one-product wonder.
I just didn't know. I am glad to see that people are actually writing about this issue in such a smart way, showing us all different sides to it. You are a great blogger. Please keep it up. I cant wait to read whats next.
ReplyDeleteIt is really strange that they did not see or report any such reactions in the phase III studies. In fact they categorically say that no anaphylaxis reaction was seen. I feel it was good that the Fresenius was part of the study and this was caught. After this, it would be hard for Takeda to get an approval in Europe I would think.
ReplyDelete1. FDA never asked for Recall - You are wrong at first place.
ReplyDelete2. FDA has no mechanism to detect fetal reactions- It is Healthcare providers which reports such Incident report. FDA also has no mechanism to investigate the cause as it is the Drug company responsible for submitting their clean cheat. So you are wrong again..
Rest is just BS.
A useful article, thanks. dissertation example
ReplyDelete