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Does the FDA Reject Anything Any More?

Matthew Herper is saying “No, apparently not“. And here are the numbers:

As recently as 2008, companies filing applications to sell never-before-marketed drugs, which are referred to by the FDA as “new molecular entities,” faced rejection 66% of the time. Yet so far this year the FDA has rejected only three uses for new chemical entities, and approved 25, an approval rate of 89%.

Those numbers come from a new analysis commissioned by Forbes from BioMedTracker, a division of publishing giant Informa that helps investors track events in the pharmaceutical industry. And if you dig into them, the drop is even sharper.

If you eliminate new uses for the same drug, the approval rate is more like 96%. I’m willing to stipulate that this change is real – it looks pretty convincing. Now the question is, why did it take place? I think that companies are actually doing a better job of working with the agency to run the sorts of trials that it wants to see, and gather the kinds of data that will lead to approval. I also wonder if we’ve seen an increase in post-approval studies. Neither of these are necessarily bad things, as long as the FDA’s priorities are straight. But that’s the big question – has the agency eased up?

Herper’s article is open to the possibility. If that’s the case, then we should see an echo effect over the next few years as problematic approvals run into trouble. But there’s another possibility, that a number of not-great-but-not-unapprovable things are getting through – incremental advances. You hear that sort of description and you think “me-too drugs”, but that’s not necessarily the case. This can happen in totally new therapeutic areas, too, where some new drug is the first thing to treat patients, but doesn’t do it that well.

There’s a sports analogy here. Years ago, Bill James wrote about the baseball truism that “the good teams win the close ones”. He showed that this wasn’t true – in fact, the really good teams tended to have somewhat worse-than-average records in one-run games. That’s because, for one thing, they didn’t have as many one-run games – they tended to win pretty convincingly, and rarely got blown out. And when they did lose, a higher number than usual of those losses were where the other team just squeaked past them. When you think about it, a good record in one-run games really seems unlikely for a truly powerful team.

And so for drug approvals. A totally new therapeutic area rarely opens up wide enough for a mighty curative blockbuster therapy, at least not at first. Medicinal chemistry gets a toehold on some cliff face that no one else has ever climbed, and with any luck, later explorers will find some better way up. So if a number of marginal drugs are getting though, that might actually be a sign of innovation. More data!

9 comments on “Does the FDA Reject Anything Any More?”

  1. MTK says:

    Has the number of NME submissions over similar timeframes decreased?

    If it has then that it might not be surprising that approval rates have gone up markedly. The companies simply aren’t submitting things until they’re sure it’s going to get approved. Or companies are dropping programs without a very good chance of success.

  2. I don’t have the data in front of me to back this up, but hasn’t the shift in therapeutic area focus had a huge impact? Getting the FDA to approve a PCP-prescribed drug that is widely used for a moderately severe disease is a lot harder than getting an oncology or orphan disease therapy approved where there are no or few options.

    I remember seeing VC data from a few years back that suggested over 50% of funding goes to oncology alone. Add in the many new orphan drugs and i’m not surprised approval rates have increased. It all comes down to risk/benefit. I’m glad the FDA is that flexible.

  3. Parker says:

    Pricing and economics will be a different matter…

  4. CMCguy says:

    Dumb Question IMO as looking at FDA approval rates alone probably has minimal value in addressing the question as need to look at overall drop out across clinical studies and I am not sure those have improved at all and may have gotten worse. Earlier interactions and consultation probably has indeed directly benefited odds for approval, especially related to clinical trial design, meaning that once reach submission there is greater likelihood have acceptance but overall would suggest FDA has continuously become more strict in certain ways like in regards to precise statistical measurements and interpretations where companies have been more rapidly adapted to harder requirements. The extreme costs of development has driven strong risk aversion and hence any signs of weakness may kill a project so again there is a filter that never will reach NDA submission stage.

  5. johnnyboy says:

    MTK above is asking the right question. Herper and the institute reporting these percentages should have also reported the absolute numbers of submissions – this is pretty basic statistics when you want to understand what is going on. If the number of submissions has increased at the same rate, that would bolster the argument that FDA might be more permissive. If the number of submissions has decreased, to my mind it would suggest that companies have been more careful about what and how they submit, which could explain the higher approval rate.

  6. David Cockburn says:

    I think Derek’s analysis of how progress is made in a difficult therapeutic area is correct and important. Important because we need to make things easy for not-very-good products in difficult areas.

  7. PorkPieHat says:

    This subject header about FDA not rejecting anything anymore was the topic of a post in Fierce Biotech called “The FDA Blundered Badly on the Addyi Approval”:

    “Over the last few years the FDA has prided itself on accelerating the approval process for drugs, providing faster reviews and offering a number of expert panels that lean heavily on the side of an approval. Any marginal cancer drug with a clearly defined risk profile, even if it’s a bad one, can get approved for late-stage, dying patients. Drug approvals on an annual basis have surged.

    And there’s a perfectly legitimate argument to back that up.

    But in approving Addyi, the FDA has gone overboard, exchanging greater efficiency in favor of purposeful permissiveness. And it’s lowering its standards on the risk/benefit equation by ignoring the realities of the Internet.

    The agency can’t control the viral campaign that’s already well under way. It can’t control prescribing habits or, more importantly, the demand for this drug. It can’t prevent the side effects that we will now be seeing as the drug starts to become available to a much wider population than it’s intended for. And it’s the kind of blunder that could well cost the entire industry if the inevitable backlash causes the FDA to grow overzealous about safety issues.

    This is a regulatory failure of the worst kind.”

    The whole Sprout Pharmaceuticals / Valeant story just stinks up our industry something bad. Sigh….

  8. Rule (of 5) Breaker says:

    Another possibility is that companies and the FDA are working together earlier in the
    process. I have been in pharma long enough to see the mode of operation go from
    “we don’t speak to the FDA until we file” to “let’s talk to them early on the get a read on
    this” – at least at my company, I have seen that evolve over the years. We (pharma and
    the FDA) both want the same thing (albeit for not entirely the same reasons) – useful
    treatments for patients. It makes more sense to work together than be adversarial.

  9. Anonned says:

    I agree with PorkPieHat, but the approval process of Zohydro truly reeks and I believe that the real damage to peoples’ lives will be much greater.

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