The “21st Century Cures Act” has now been signed into law. I only wish it promised the cure for some of what the 21st century has had to offer so far, but we’ll take what we can get. So what are we getting? Steve Usdin of Biocentury put it well when he said “Start with a large number of policy options, subtract any that don’t appeal to Republicans, remove any that Democrats adamantly oppose, delete any that industry hates, and kill or revamp those that FDA says it cannot live with“. I’m surprised that there’s a lot left after that process, but there is.
In addition to my thoughts the other day, I wanted to bring up some others that Biocentury identifies. Usdin’s concerned about the NIH funding provisions in the bill, because it’s so heavily tilted towards high-profile translational projects and perhaps away from basic science. There are also some significant changes in the way that even the institute’s common funds can be used that I hadn’t realized – the “other transaction authority” mechanism is significantly expanded, which seems to give the various NIH heads much more discretion about where the money will go, and how quickly. Overall, funding power seems to have been (very much) centralized, and we’ll have to see what that produces in practice.
I didn’t go into the antibiotic and antifungal approval changes in my earlier post, but the idea is that approval paths for drugs in these categories for “limited patient populations” have been enhanced. These approvals will bear special labeling and other mechanisms to keep them from being prescribed outside the group that’s been shown to benefit. Of course, if later studies show that a compound in this class can be more broadly useful, it can be taken out of this category, but overall, this seems to be a sort of “orphan antiinfective” pathway. What I’m not sure about yet is how this would work financially – would such compounds come in at the high prices that would seem to be indicated by their small approved patient population?
One area that’s gotten plenty of attention is the mandate for “real-world evidence” in drug approvals. Usdin’s less worked up about this one:
Critics of the 21st Century Cures Act have warned that it would erode approval standards by allowing FDA to approve drugs based on anecdotal evidence. This is a huge exaggeration. What Cures would do is start FDA down the long road toward relying on real-world evidence to support selected regulatory decisions. The agency would have two years to establish a draft framework for two specific uses of real-world evidence: label expansions, and supporting or satisfying postapproval requirements.
The definition of “real-world evidence” appears to be evidence obtained by other means than randomized clinical trials, which is what has people worried. But as in the above, the bill isn’t saying that the FDA can approve drugs via such mechanisms; it’s saying that after trials and approval that other means (such as “ongoing safety surveillance, observational studies, registries, claims, and patient centered outcomes research activities“) can be brought in for label expansions, etc.
In another area, explicit “right to try” provisions did not make it into the bill. What’s there is more guidance on compassionate use provisions. Companies working on drugs for life-threatening conditions will be required to make their policies on compassionate use publicly available, with contact numbers, etc., but there are no requirements for any of these compounds to be made available – the publicly stated policy, in other words, could be “We do not make this compound available for compassionate use”, and that’s within the law.
The Biocentury article is particularly good on the regenerative medicine parts of the bill. There was an awful lot of back-room scuffling in this area:
FDA and the Alliance for Regenerative Medicine (ARM), an organization dedicated to advocating legislative and regulatory policies, beat back attempts to allow marketing of certain cell-based therapies based solely on small Phase II trials.
FDA Commissioner Robert Califf co-authored an article published Nov. 30 in the New England Journal of Medicine that addressed some of the arguments that had been presented to Congress to support reduced safety and efficacy requirements for regenerative medicines. According to the article, “the assertion that existing standards for regulatory approval are too rigorous for stem-cell therapies results largely from a lack of familiarity with the available pathways for developing cellular therapy products and from the lack of a systematic, facilitated approach to assembling the clinical data necessary to support the licensure of stem-cell therapies produced by individual practitioners at different sites.”
The final version of the bill, which ARM supports and which has not raised objections from FDA, would create a system for designating therapies as regenerative advanced therapies, and would treat designated products like breakthrough drugs. For example, sponsors of designated products could get meetings with FDA early in product development to discuss potential surrogate endpoints.
The actual standards for approval (and even accelerated approval) in this area have not changed, though. There are new provisions for post-approval studies and further demonstrations of efficacy, but you’re still going to have to show efficacy (and safety, of course) to get through the first time.
One thing that I don’t think many people talking about this bill have realized, and that Usdin emphasizes, is that many of its provisions are going to come right back before Congress pretty shortly, when user fees for the FDA will come up to be reauthorized. A lot of things are going to be thrown into that legislation, and you can expect that people who particularly dislike some aspect of this new law (or particularly think it missed something that might have been taken out along the way) will come back around for another try.
There’s another wild card, too. Depending on who the next FDA Commissioner is, the emphasis placed on all these things could well change a bit. I know that there have been a lot of stories recently about candidates with what appear to be pretty radical ideas, but I’ve already gotten tired of the new administration’s reality-show approach to floating names for these things, and I’m going to reserve my comments for when someone actually gets nominated. The President-Elect is already (in my view) well on his way to wearing everyone out by throwing shiny objects all over the landscape, and we’ve just barely made it out of the first week of December.
In all the horrified talk – and some of the horror would be justified – it’s worth remembering that the FDA’s mandate to consider efficacy and safety is not up to the desires of any one commissioner or administration. It’s part of the legislation establishing the entire agency. If you want to change that, you have a lot more shovel work to do. In general, I think that the incoming administration will be finding out (as many of them do) that causing Giant Transformational Change is not so easy in Washington. That’s partly by design; our entire system is set up to make it difficult to get things done, for fear of what might happen when it’s too easy.
This causes periodic cries from both the Right and the Left about how it keeps Good Things from being showered on the country by the Good People when they finally defeat the forces of darkness and get into office, but that’s how it is. I’m fine with that, and in fact, the main thing I’m looking out for are attempts to shortcut around these checks and balances. For example, I really dislike the expansion of executive power that’s taken place over the years, not least in the past eight, and would like to see some of that stuffed back into the box. Give me more gridlock.