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!