Avastin at the FDA: Passion Should Lose

Jun.30.11 | About: Roche Holding (RHHBY)

Today is Day Two of the FDA's hearings on Avastin for metastatic breast cancer. (Note: if you want to follow things in near real time, I'd suggest a Twitter search for #Avastin. I can particularly recommend Len Lichtenfeld's feed.) This has been a very contentious issue; as most of you know, Avastin was provisionally approved for these patients, then pulled when more trial data came in showing no benefit. Roche (OTCQX:RHHBY)/Genentech's team is now appealing that decision, and the questions are:

  1. Should Avastin be approved for metastatic breast cancer patients? The answer to this one is "depends on the evidence for it." So ...
  2. Is there enough evidence to decide one way or another? Both the FDA and Roche seem to think that there is. The problem's that they come to opposite conclusions. So ...
  3. What's the risk/benefit ratio for Avastin in these patients? Now the serious arguing starts. Avastin is not without its serious side effects -- but metastatic breast cancer is a terrible disease. The initial reports were promising, but none of the larger follow-up trials have really confirmed those results. Genentech is proposing still another confirmatory trial, with the drug to stay approved during that period, but the FDA seems to be arguing that leaving the drug approved for this indication will hurt more people than it helps.

And all of this is being done against a backdrop of emotional cancer patient testimony. The problem with that is summed up by one of the most fervent advocates, Patricia Howard, who told the FDA: "I’m not just a statistic; it is in your hands to ensure that I don’t become one."

It pains me to say this, but she's wrong. If we're ever going to get anywhere with cancer (or any other disease), we're going to need all the statistics we can get our hands on, and no amount of passionate testimony should be allowed to move one number in them. I've had family members with cancer; I've seen good friends and plenty of good people die from cancer. But cancer cells do not care about how strong your feelings are. The growth factor receptors, the checkpoint kinases, the apoptosis regulators, the metabolic enzymes and cell adhesion proteins: They don't give a damn; they have no damn to give. We have to fight them on those terms, on that battlefield, because that's the only one that matters and the only one where they can be defeated.

As it stands, I agree with the FDA's position: I don't think that Avastin has been shown to offer enough benefit. The 2008 provisional approval was already arguable -- the agency went against its own advisory committee just to do that much -- and the subsequent data have made it even less tenable. If we're going to have provisional approvals, then they have to be able to be taken back. And if we're going to evaluate drugs by their risks versus their benefits, then Avastin -- for this indication, in these patients -- doesn't (to my eyes) seem to make the cut.

If, on the other hand, you disagree with the provisional approval process, fine. Propose something more useful. If you disagree with the risk/benefit analysis in this case, then you should bring some new numbers or some new arguments (which is what Genentech is trying to do right now, as I write this; I hope that it doesn't slip over the line while doing it). If you disagree with the whole idea of risk/benefit analysis, then ... well, you'd better have something more useful to offer. And you'd better be sure that it doesn't end with the decisions going to whoever is the most passionate and tearful in making their case. That won't end well.

One more side issue: You'll note that I've done this whole blog post without talking about the price of Avastin. That's because I don't think that the price is the issue at all here. This is not a healthcare-rationing issue, no matter how much some people would like for it to be. Roche gets to charge what it thinks Avastin can bring; it and Genentech have put the time, effort, and money into the drug. But for metastatic breast cancer, as I said here, Avastin doesn't seem like a good idea even if it were free.

Disclosure: None