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Drug Development

Drug Approvals Over the Last Ten Years

Here’s a look back at the last ten years of FDA drug approvals, and it’s a pretty encouraging read. As the authors mention, in the early 2000s there was quite a bit of worry about the directions that drug research (and drug approvals) might be taking. We were getting to the end of some of the popular mechanisms from previous years, and a lot of big drugs were coming towards their patent expirations. But the past ten years went better than one might have expected. There were 18 approvals in 2007, and 21 approvals in 2010, and the total has never been that low since.

It’s important to keep the time lag in mind for all this – drug approvals are based on research and on decisions made years before. The paper notes that the drugs approved in the last ten years have taken an average of 8.7 years from the first Investigational New Drug filing (permission to head into human trials, basically) until the goal line of approval of a New Drug Application. But that covers a range of 2.2 years on the fast side (for osimertinib, which was targeted at a particular EGFR mutation in non-small cell lung cancer) all the way out to ibalizumab (a CD4 antibody for HIV therapy, which took 16 years) and flibanserin (a serotonin agonist for sexual dysfunction, which took 18 years). Overall, the median time to approval has remained pretty constant since the mid-1990s (somewhat faster regulatory approval and somewhat slower trials have balanced out).

As for therapeutic areas, 25% of all the drugs approved during the 2010s were for cancer (103 of them in total), 14% for infectious disease, 12% for CNS disorders, 7% for metabolic disorders, and 6% for cardiovascular indications. Those last two categories have a noticeable slowdown compared to prior years, which is surely due in part to the number of approvals in past decades. The easier mechanisms have been hit pretty thoroughly, and there are quite a few therapeutic options (some of which are generic drugs by now). So if you’re going to make a splash in diabetes or heart disease, you’ll need to have something that really stands out. This is not a new trend; it’s been gathering for quite a while, but the generic status of drugs like metformin and atorvastatin just nails that down even harder.

That oncology figure includes the first wave of immuno-oncology drugs, of course, and it seems certain that the 2020-2029 period is going to have plenty more of them. We’re also likely to see the same trend there as in the rest of oncology – more and more targeted therapies, tied to particular subfractions of patients as identified by diagnostic testing. Indeed, there’s been a trend (as with ibalizumab and others) for such a diagnostic test to be developed and approved along with the drug. It’ll be interesting to see how far this can go. It’s another trend that’s been coming on for a long time, and there are two big factors that have to balance out: a smaller patient population means a more expensive drug, in general, but targeting particular populations in this way can also lead to much greater efficacy. It had better, anyway.

It might have been surprising to see infectious disease as the number two category – until you think of the two viral diseases that we can really do something about with small molecule drugs, namely HIV and hepatitis C. I’ve said it before – if you’d told people in the early 1990s that HIV would turn into one of the most thoroughly treated viral diseases with a whole list of therapeutic options, they would have checked to see if you were showing other signs of disorientation. But that’s just what has happened. Hepatitis C has just been driven into the ground by a whole list of curative treatment regimes approved since 2010, but the contrast between these two diseases and the rest of the antiviral field is acute – not to mention the contrast between the antivirals and the antibacterials, where no such sweeping advances have been made. It definitely helps that viruses have fewer working parts, and it also helps to take ten (or twenty) years to bear down on those particular mechanisms, as opposed to the situation with our current pandemic. There have been 15 antibacterial drugs approved in the last ten years, but they’re almost all from variations on existing themes.

The authors of this review were as surprised as I was to see the CNS drug approvals ranking as high as they are, considering how many big companies have abandoned the field (either partially or completely). But it’s worth noting that these approvals haven’t been as much in the “classic” CNS areas such as schizophrenia and depression, but rather in multiple sclerosis, migraine, and others. The Alzheimer’s drug approval landscape remained the same windswept tundra as usual, but a glance at the headlines in the field will show you that several companies are spending impressive amounts of time and money trying to change that. What those efforts will actually yield (or have actually yielded, in Biogen’s case) will, as always, have to be established by brutally long and expensive clinical trials, which are among the roughest slogs in the whole drug industry.

The review points out that first-in-class approvals seem to have surged over this period compared to the previous ten years. An average of 37% of approvals were in that category, never dipping below 32%. I actually expect that trend to continue, given the number of unusual mechanisms and targets that seem to be out there these days. Not all of those things are going to work out, of course, but in general I think there’s a more varied drug discovery/development landscape now than there has been during my whole career (1989-present). It makes me very happy indeed to say that, on several levels. On the scientific level, it’s great to see so many new modalities getting their time in the clinic (antisense, siRNA, CAR-T, CRISPR, targeted protein degradation, exon skipping and more). And it’s also good news in the medical sense, since so many of these mechanisms are being deployed against targets and diseases that have had few or no therapies available at all. It’s a great time to be doing this work, to be exploring these new ideas, and to be attacking these intractable disease. Let’s keep it going!



24 comments on “Drug Approvals Over the Last Ten Years”

  1. ezra abrams says:

    ACS website, quote
    A Decade of FDA-Approved Drugs (2010–2019): Trends and Future Directions
    Purchase this article for 48 hours $40.00

    $40 dollars for **two days**

    The Paywall is so high cause the article is part of our Healthcare system ?

    1. Kenneth Kelly says:

      The Journal of Medicinal Chemistry is not part of the healthcare system. It is a publication of the American Chemical Society.
      FWIW, the 32 pages of supplementary material are freely available.

    2. CET says:

      The paywall is so high because journal publishers have turned rent-seeking into an art form.

      1. Thomas says:

        25 years ago I worked for a scientific publisher. There was some industry wide training on how to keep increasing subscription fees, and strategies to follow so that customers who balk at the costs will take your new offerings.
        Which you will also increase in price.
        I decided I wanted to do more with the content.

      1. Jim Van Zandt says:

        Which hasn’t been working for me, for the past few weeks. Reportedly ISPs are under pressure to block it.

  2. Marko says:

    “Brits are calling out the ‘dystopian’ and ‘post-apocalyptic’ American pharma ads that aired during Oprah’s interview with Meghan Markle and Prince Harry”

    This dystopian health care world is probably coming to the UK, via the ongoing incremental, barely-noticeable privatization “improvements” of the NHS. Don’t worry, though, when it happens , you’ll quickly adapt to it as it becomes the “new normal”, and will even begin to defend the dystopian new regime against any outside criticism.

    It’s actually quite an impressive process to watch unfold. When it comes to slow-boiling frogs, these guys are master chefs.

    1. JeffC says:

      I always find these “privatize the NHS and it’ll be like the US soon enough” quite frustrating and fundamentally ill-informed.

      There seems to be this belief in the UK and the US, that there are only two types of healthcare system, the US one and the UK one. The reality is that pretty much nobody else in the world has chosen to operate their systems like either the US or UK. Converting either system into the other is not a function of either privatization os socialization. Both setups have great flaws (and strengths), but it seems fairly obvious that neither setup is works well.

      The NHS will not turn into the US setup; it would be hard to replicate the fragmentation and dysfunction of the US system, in the same way that bringing more equitable access to the US system would not turn it into the NHS. There is very much not a straight line between the two setups.

      And to be clear I do not think the current UK government is well placed to “improve” the NHS

    2. EB says:

      As my wife will attest, I routinely comment when these ads are on, which are fairly guaranteed to happen every commercial break. I recall once a few years ago a guy who appeared to have tennis elbow and the ad was for an immune modulator for rheumatoid arthritis. I mean, there probably aren’t any weird long-term side effects from 10% of the US population being on some immune modulator or metabolic metformin-like hack, so lets now worry or even look, right?

  3. Dan says:


    1. Ray says:

      “People ask me to predict the Future, when all I want to do is prevent it”

  4. Matt says:

    Curious what percentage of approvals relied on surrogate endpoints (see doi:10.1001/jamainternmed.2020.2250)? It definitely seems some of cancer approvals driven by more relaxed regulatory requirements.

    Surprisingly high number of first-in-class though.

  5. Patrick says:

    If I may ask… a few years ago, wasn’t all the conversation around drug discovery struggling/slowing/failing to produce new things? How the rate of return on R&D was dropping, etc?

    Did something change? This discussion seems like it’s been good for a while now?

  6. Rock says:

    In a recent role, I was part of a team that would discuss various med chem topics with the department. Each February we would cover new drug approvals from the previous year. Out of interest, I added a new twist, and also went back and looked at the outcomes of the drugs from six years prior. I figured that was enough time to reach full market penetration. As expected, the results weren’t as rosy as the approval count would suggest. Yes, there were a few blockbusters in there, and a larger group of moderate successes, but there was also a majority that were either discontinued or languishing with sales that would never recoup their development costs. This data was in line with published reports that suggested that only a relatively small percentage of drugs produce profits, something the general public is unaware of.
    Don’t get me wrong, I agree that the recent trend in approvals is great. Just remember that they are not all created equal.

    1. Petros says:

      An analysis by Grabowski and Vernon in 1994 reported that most drugs failed to cover the average R&D cost of drug development so it sounds like little has changed

      1. MrXYZ says:

        I remember when I was in college in the 80s, we had a speaker from a pharma company talking about the development of a particular drug (I think it was an ocular drug). It seemed like a relatively small-ish patient population and I remember someone asking how they made money on a drug like that (given the development costs). He mentioned that most drugs did not make money and that a few blockbuster drugs paid for everything else. This was probably 1987 or 1988.

        This is how drug discovery has worked for a long time.

  7. Den Rogers says:

    The makers of Flibanserin did a very poor job of advertising.

  8. Anon says:

    Interesting how the fate of drug discovery/development mirrors the fragmentation we have seen in media/entertainment over the past few decades…we’ve gone from mass market/blockbuster drugs (think Dyazide/Zantac/Lipitor) and single source (Walter Cronkite/Seinfeld/Sinatra) to an atomized market catering to niche tastes (drugs/biologics for niche conditions/Netflix/Newsmax-MSNBC)…

    The question is given the small patient/viewer volumes, how does one fund and sustain innovation and the product pipeline? In the case of news/entertainment, subscription and licensing fees keep the whole enterprise afloat, with individuals voluntarily subscribing to services at a low monthly fee. But how is this going to work in the Rx world? Jack up prescription costs to unsustainable levels? Or is some kind of gov’t/taxpayer subsidy going to be necessary to fund and fuel the entire drug discovery/development enterprise? If you drop salaries and employment prospects for our scientists, all you will do is drive the “best and brightest” to more lucrative fields. This atomization of disease states and patient populations is going to be the biggest challenge going forward for drug discovery. Someone has to pay for the entire ecosystem going forward. Will it be an individual burden or a subsidized cost?

  9. Marko says:

    B.117 not as high in NYC as I would’ve thought – only ~12% in late Feb. The home-grown variant, B.1.526, was more prevalent then at 39% :

  10. Marko says:

    Moderna Announces First Participants Dosed in Study Evaluating COVID-19 Booster Vaccine Candidates

  11. Marko says:

    The bottom line on all this :

    “Over the past 40 years, the United States has gone from having a life expectancy near the average for upper-income countries and average per capita health care costs to being a negative outlier .”

  12. Gary Cornell says:

    You know it’s mindboggling to me that the super-rich philanthropists and foundations haven’t made anti-bacterials i.e. dealing with drug resistance to antibiotics one of their highest priorities. Are antibiotics just not sexy enough for the big foundations and super-rich people?

  13. ralph says:

    I guess this is more or less an inactive thread, and I guess there will almost definitely be a post about this soon. But what do people think of the Eli Lilly announcement today as to the Phase II results of their anti-beta amyloid mAb? I know Phase III is the graveyard of Alzheimer’s drugs, but it seems remarkable to me that all the most recent drugs in this class seem to be inducing a similar reduction of cognitive decline (~30%). Maybe it’s an indication that there really is something to the amyloid hypothesis after all?

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