The 21st Century Cures Act has some important provisions that would impact the stem cell and regenerative medicine field. What is driving these efforts is a widespread sense that the status quo of regenerative medicine oversight isn’t working very well.
I’m talking with key stakeholders and still trying to sort out my thoughts on the stem cell provisions in Cures. What would it mean? Cures’ language on stem cells is nuanced and its provisions also are not so black and white as REGROW was in my view.
You can see my interview with ARM’s Executive Director Michael Werner on Cures here. ARM supports Cures. ISSCR issued a statement this morning on Cures, which is upbeat but stresses the importance of data. The statement is not a clear thumbs up or down. Earlier this year, both ARM and ISSCR opposed REGROW.
Overall, there are both potential risks and benefits to Cures’ stem cell provisions, which I discuss below. Note that this post is focused primarily on the stem cell-related provisions of Cures. There is ambiguity in terms of how Cures will affect NIH overall or have broader outcomes for the life sciences.
Potential upsides to Cures for stem cell research. One possible benefit of the Cures regenerative medicine provisions is that some high quality stem cell therapies that ultimately will be proven safe and effective would likely get to patients more quickly and help patients sooner. That’s a big deal. For biotech the major plus would be that they will have to spend less money to get therapies further in the trial pipeline. Since we as a field need stem cell biotechs to be successful in order for all of us collectively to help the most patients, the benefit for biotechs would likely yield some benefit for the field. Another possible plus here with Cures is the focus in the language on the need for standards for regenerative medicine, which have been lacking in the field.
Possible risks. A major concern is that some stem cell therapies that are not ready for primetime may move forward anyway into patients and potentially harm them, depending on how the Cures language translates into actual changes in oversight. The “real world evidence” provision in Cures is causing some unease as it could be at the expense of the gold standard requirement of data from RCTs. There is also uncertainty over the stem cell devices provisions in Cures, which some view as not strong enough. Finally, my impression is that too much of what in the way of data that would today be required at the pre-approval level, would be shifted to post-approval under Cures, which could substantially increase risks for patients. ISSCR places weight on the need for rigorous data as you can see from well this part of their statement:
“Of paramount concern is that the streamlined process for FDA review and approval outlined in the bill should not compromise the rigorous review of scientific and clinical evidence required to ensure the safety and efficacy of regenerative therapies”
I strongly agree with this statement.
What qualifies as an advanced regenerative therapy? One of the most important stem cell-related provisions in Cures is the third criterion for definition of a product as an advanced regenerative therapy that qualifies for acceleration:
“preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such a disease or condition.”
Who decides on this evidence and how? It’s unclear. The word “preliminary” could be an issue here in terms of how it is interpreted.
Senator Elizabeth Warren is one of the fiercest opponents of Cures overall and she specifically weighed in with her objections to the stem cell provisions:
“Warren criticized provisions designed to speed approval for stem cell therapies. Referring to a major Republican donor who would stand to benefit from the provisions, “This megadonor has poured millions of dollars into Mitch McConnell’s personal campaign coffers and into his Republican super PAC, and now he wants his reward. So the Cures act offers to sell government favors.”
Overall gestalt. My sense right at this moment is that if the 21st Century Cures Act passes with the current stem cell provisions that it will kick off a high-risk, potentially high-reward regulatory experiment on regenerative medicine here in the U.S. It’s unclear if on the whole there would ultimately be more benefit or harm to patients and the field. We don’t know the results of experiments in advance, right? Another major factor in how this plays out will be how the FDA more broadly fares under the new administration.
The bottom line is that for me at this time I can’t really say I strongly oppose or support the Cures stem cell provisions because there is so much uncertainty about how it would all unfold and as discussed above there are potential benefits and risks. My initial impression is that there are somewhat more potential risks than potential benefits, but it’s not very clear cut. What do you think?
Forgive my cynicism–and please correct me if I’m wrong– but a bill that was heavily lobbied for by Big Pharma and tech industry is immediately suspect. As far as I can tell, it cuts public health in favor of high-tech drug development. Not to say some good might not come out of it, but it sounds like more neoliberal health policy to me. Good summary of winners and losers here: http://www.npr.org/sections/health-shots/2016/12/02/504139105/winners-and-losers-if-21st-century-cures-bill-becomes-law
Apart from the accelerated approval aspect, the text of the Act is very broad and only makes inferences to safety and quality – does this mean that interpretation will be left to the FDA?
REGROW Act described provisions to allow non-homologous use and the use of “more than minimally manipulated cells” in unregulated clinical practice, but the Cure Act makes no such detailed descriptions and doesn’t propose a more acceptable option. How will this help us to move forward on these issues?
I have not had the opportunity to read the proposed Cures Act legislation, so I may be suggesting something adequately addressed.
An important / critical feature of any attempt to speed treatments to patients in the absence of “definitive” safety / efficacy is follow-up and collection of data during this time. If the Cures Act has clear requirements for treated patients being followed with data collection such that safety and efficacy can be objectively determined over the course of many patients and a time frame consistent with the experimental treatment’s expected potential effects (e.g. a stem cell treatment could potential have effects, both positive and or negative, over the lifetime of the treated patient), there may in fact be conditions for which early “role out”, based upon limited Phase1/2 data, of a potential treatment is warranted.
I believe the Japanese regulations have something in place along these lines: after a certain length of “conditional approval”, data must be presented showing safety and efficacy in the larger population which was allowed to be treated under the conditional approval pathway.
thoughtful questions, but I think the wrong balance. Yes, clearly earlier/quicker = more risk to patients; but the whole point of things like the Japanese approach; and various right to try efforts, is to say that we understand that there are patients whose condition(s) Justify more risk at the Patient’s discretion. The rules need to change to ensure absolute transparency into the additional risks, not slow things down because there Are additional risks.
As someone with moderate stage age related macular degeneration I have a personal stake in the potential for the use of stem cells in future treatment if/when it might be indicated in my case. I also witnessed my Dad have to cope with the aftereffects of more rudimentary laser treatments 20 years ago.
Notwithstanding those personal concerns my 30 year career in health care services and my experiences with my wife having survived breast cancer treatments make me cautious about the use of any treatment regimen before there is very solid data to support it. Seems to me that CURES would allow too much leeway for the profit motive to affect clinical, treatment decision makong
Paul,
This Cures Act has gone political ……..How will these provisions that would impact the stem cell and regenerative medicine field compare with Japanese regulatory environment