Responses to the Avandia panel have been all over the map, as cleverly noted on the Wall Street Journal health blog. Avandia is “dead” (Forbes), or, perhaps worse, “now a Zombie” (BNET). By contrast, others thought the panel granted Avandia a “reprieve” (Wall Street Journal and that Avandia would now probably be allowed to stay on the market (Los Angeles Times, Pharmalot).
All these views are right though I think they miss some of the complexity of the issue. For instance, in my view Avandia took a big hit, but GSK actually came out better than expected. Here’s my scorecard, with annotations, of the winners and losers:
Avandia (rosiglitazone) lost. 22 out of 33 panelists thought the drug should either be withdrawn from the marketplace entirely or have severe restrictions or limitations imposed on its use. The fact that only a plurality of panelists voted for withdrawal should be cold comfort to the drug’s supporters. You know you’re in trouble if the best argument supporters can make about a drug is that it probably doesn’t kill you or harm you and that maybe in a small percentage of people it will help where other drugs can’t.
GSK didn’t lose, which means it won. I know very little about the business side of pharma, but it’s hard to imagine that anyone at GSK has seriously held out hope for the revival of the Avandia franchise. Unless they’re complete idiots, I assume they’ve tried to figure out a major course change that won’t destroy the entire company in the process. Presumably they’ve been looking for a way to extricate themselves from the whole entire mess without entirely losing either their reputations or their shirts. They haven’t done too well on the reputation front lately, but by retaining their shirts they probably figure they can buy back their reputation in the future. The fact that the FDA will likely not withdraw the drug presumably leaves them in a better position to fend off lawsuits.
Actos (pioglitazone) is the biggest winner, but watch out. Did you see the full page ads in Thursday’s newspapers? Look for a lot more of these. Again, I don’t know too much about the business side, but I’d be surprised if Takeda didn’t sell a whole lot more Actos in the future. Just one word of caution: remember that one of the reasons for the fall of Avandia was the tidal wave of consumer ads for the drug. It’s just possible that none of the Avandia mess would have happened if it had chosen to fly under the radar and “settle” for a more modest place in the market. Compared to rosiglitazone the data for pioglitazone looks good, but when scrutinized closely there are many out there who are also uncomfortable with the pioglitazone data. There just might be an ambitious young Nissen wannabe out there who will want to make his bones with an Actos “hit.”
Nissen, Graham, Marciniak, Wolfe, Furberg, Grassley and company won and lost. They won because, as stated above, 22 out of 33 panelists adopted their fundamental perspective and said that rosiglitazone was either worthless or nearly so. They lost because they refused to accept that it was even remotely ethical to leave Avandia on the market. Due to this intransigence, they snatched defeat from the jaws of victory.
Long time FDA leaders like Woodcock, Ungar, Jenkin and colleagues apear to have won. I’m no FDA kremlinologist– I can’t even figure out my way around the FDA website– but it seems to me that they were auditioning in front of Hamburg and Sharfstein to keep their jobs. I’m sure they took comfort from Marvin Konstam’s statement at the end of the session that the FDA was “not broken and doesn’t need to be reorganized,” though his exhortation to everyone at the FDA to play nicely together in the future may fall on deaf or stubborn ears.
RECORD loses and TIDE wins. I can’t remember ever seeing a trial so thoroughly discredited as RECORD. Even panelist Marvin Konstam, who is not known to be a industry critic, had scathing words to say about the trial. This can’t be good for Quintiles (the CRO that ran the trial) and it will probably mean that clinical trials will undergo a lot more careful scrutiny and auditing in the future. On the other hand, despite concerns that it may never be finished, TIDE ultimately received a strong endorsement. Many observers believed that the presentation by Gerstein, the TIDE PI, was one of the highlights of the two-day session. One grizzled veteran journalist even said the talk made him tear up, though I think that’s going a bit far. Importantly, it’s likely that with Avandia remainining in the market, the clinical trial community, along with cardiologists and diabetologists, will circle the wagons around TIDE and do everything to keep it alive. What choice do they have? (Click here to read a letter to the FDA from Salim Yusuf, the co-PI of TIDE.)
Surrogate endpoints lost. The real question now is how to replace them and not make it nearly impossible to get new drugs approved.
Finally, academics, journalists, consultants, analysts, and pundits were winners, along with the hotels and conference centers in Maryland, where there will undoubtedly be many more controversial and contentious FDA panels.