A recent comment asks why there's all this wailing about shrinking drug-company pipelines - how did it happen? I've gone into this topic before over the years (the blog's now over 4 years old, which I can hardly believe), but it's worth a quick summary. Here are some reasons - reasonable people can and do add more, and argue about how much importance to assign to each:
1. We used up all the easy targets. That can't be completely true, but still, there's something to it. I'm fond of pointing out that there aren't many home runs like angiotensin converting enzyme out there these days. Ah, ACE - an enzyme, of a class that we know we can inhibit with small molecules, that's right in the middle of a key pathway for a condition affecting millions and millions of people. You could say similar glowing things abouit HMG CoA reductase (the target of the statins). One of the hopes of genome sequencing and mining was that there would be some more of these out there that no one had discovered. This expectation has not aged well.
2. We know too much. There are plenty of drugs on the market that looked perfectly fine back when, but wouldn't go anywhere today. You can start with aspirin. We have so many more assays and counterscreens going now that it's a wonder anything makes it through at all.
3. We're competing against ourselves. As time goes on, and we gradually discover things that work for a reasonable number of people, we have to look harder for unmet medical needs. There aren't any perfect drugs out there, of couse, but there are still some areas which are pretty well served. The bar is (or at least should be) raised higher each time a new drug comes on the market.
4. We're left with really hard diseases. This is a corollary to the previous point. The big unmet medical needs are often unmet for very good reasons. Alzheimer's is a good example - big (and growing) market, lots of human suffering, current therapies almost completely inadequate. But getting a new Alzheimer's drug off the ground is a hideously hard task, not least because we still don't understand the disease very well.
5. Financial and managerial mistakes. It's always easy to use this as an excuse, no matter what the industry. But nevertheless. . .you can argue that some of the mergers that have taken place in the drug business haven't helped anyone much, and may well have harmed things (at least in the shorter term) through disrupted productivity. And even when the dust clears, big companies have their own set of problems.
Another mistake in this category: companies have in some cases also spent too much time searching for great big blockbusters, at the expense of potentially putting several smaller drugs onto the market. If you live by huge whopper home runs, you often die by them too, when the patent runs out.
There - those are a few I can think of immediately. What have I left out?