Some Detail on Symlin's Rocky FDA History


#1

The front page of the October 26, 2005 edition of The Wall Street Journal featured a disturbing article on what I would call a rogue FDA reviewer named Dr. Robert Misbin and his efforts to see that Symlin did not get FDA approval, and his subsequent efforts to try and bypass his own boss and the agency’s approval of Symlin by trying to make an issue of hypoglycemia, an adverse effect that is only caused by insulin, not by Symlin alone. Dr. Misbin even went so far as to send a letter to Mothers Against Drunk Driving, urging the group to post the Symlin warning label on the MADD web site. In his letter to MADD, Dr. Misbin said the FDA removed him from the Symlin review “after I expressed concern that this drug might increase the risk of motor vehicle accidents.” I wrote more about this in my October 27, 2005 blog posting.



The bottom line, at least in my own opinion, was that Dr. Misbin’s actions did not seem justified, as there was a body of published data (including at least one article which was co-authored by the current American Diabetes Association President Dr. John B. Buse) to support Symlin at the time of its application with the FDA. Therefore, I believe the FDA’s decision to approve Symlin was the right decision (IMHO), which is why his efforts failed to derail Symlin’s approval.



The reason I believe the approval was the right decision are twofold. First, Misbin’s concerns regarding hypoglycemia should not have been directed towards Symlin, as the hormone amylin (which Symlin is a synthetic version of) cannot cause hypoglycemia, only insulin can do that. Thus, his critique should have been directed at insulin – which no doubt, would have been career suicide for him, which is why he wanted to derail Symlin’s approval (mainly because he believed he could do so). He didn’t graduate with a doctorate because he was a complete idiot!



My second issue was that Misbin also neglected that there is really no comparison between biomedicines and chemical drugs, even as far as adverse effects are concerned. In most cases, the dosage of a biopharmaceutical (especially synthetic versions of human hormones) can be adjusted, and the side effects are then mitigated. However, the same cannot always be said for chemical drugs. Yet Dr. Misbin made a direct comparison between Symlin (a biopharmaceutical analog of the human hormone amylin) and the chemical drug known as Rezulin was developed as a treatment for type 2 diabetes. Rezulin was always a foreign, chemical substance which did not exist anywhere in nature, unlike amylin. In effect, Mispin was arguing with nature in that regard.



Also, Symlin was the first fundamentally new treatment for type 1 diabetes since the discovery of insulin in 1922, bringing the grand total to two (actually, Symlin cannot be used by itself, so does that even count as a whole treatment?), which should have been taken into consideration. He was trying to limit treatment options for a segment of patients that have comparatively few therapeutic treatment options, and that should have been weighed in his decision, but alas, it wasn’t.



Other diabetes clinicians did not share his perspective. Notably, Dr. Steven Edelman, assistant professor of medicine at the University of California San Diego School of Medicine, wrote to the FDA in 2003 in support of Symlin, "Our country has tunnel vision in that a drug is judged on its ability to drop the A1c and is blinded to the many other important aspects that a therapeutic agent for diabetes can offer."



The link listed below is the URL if you already have paid access to The Wall Street Journal:

http://online.wsj.com/article/SB113028992607079538.html



I’m not sure what anyone else’s thoughts are, but I’m curious to hear others’ input is (especially those with type 1 diabetes, as we already suffer from an impaired counterregulatory function which is generally less of an issue in patients with type 2 diabetes) regarding Symlin and hypoglycemia – does it increase the likelihood or perhaps only during the initiation in getting to full dosages? Perhaps that’s another topic, but I’ve actually read some doctors feel that by reducing total daily insulin dosages, Symlin may actually lead to a reduction in hypoglycemia.