Reality check: challenges to getting stem cell treatments to the clinic

It has been a rollercoaster few months between the anti-hESC court cases as well as Geron and ACT receiving the OK from the FDA to proceed with initial clinical trials of stem cell-based therapies. It’s OK to be excited about the clinical trials and I for one am, but we have to avoid getting ahead of ourselves or having unrealistic expectations moving forward. So let’s take a breather and do some analysis of where we are and the road ahead.

As someone who has been in science 2 decades, I have been involved in a lot of different kinds of research and experiments. I’ve never been more excited about a type of research than I am today about stem cell research. However, we face critical challenges to get stem cell-based therapies to the clinic. Often these challenges are overlooked or ignored, but that doesn’t make them any less real. Understanding these realities is crucial for having a vision of what lies ahead and wisely picking the best roads to take.

Some of the challenges can be illustrated by looking at the 2 biotech companies in the news recently, Geron and ACT, for getting FDA approval to proceed with their initial clinical trials.

One of the key challenges to getting a drug to the clinic is simple, but devilish: money. Research is expensive no matter where you are or what field you are in, but getting a drug (and remember stem cell based therapies are indeed considered drugs) all the way through clinical trials to final FDA approval to actually be used to treat patients is incredibly expensive.

Geron and ACT know this well.

It can costs $100s of millions and even then you are not guaranteed of a profit for the company even if you are allowed by the FDA to market your drug. When we are talking about helping thousands or millions of patients, it may seem crass to talk about profit, but if companies cannot make profits using stem cells, they and other companies will not continue to research and develop such therapies. We have seen some recent major drug development projects be KO’d after $100s of millions were invested and the products had gone through some stages of trials. They had nothing to do with stem cells, but they are a sign that caution is in order.

Another major challenge for getting stem cell drugs to market is having your drug successfully navigate the trial process itself. There is a reason they are called ‘trials’ and that is because the drug in question goes through many steps in being evaluated for pharmokinetics, safety and efficacy. Drugs can fail at any step of the way, and most often drugs do fail at some point.

As a stem cell scientist, I see clinical trials as experiments. They are very unique and highly regulated experiments involving human patients, but they are experiments nonetheless. As much as we think we know what is going on and we have strong preliminary data, in science most experiments either do not work or do not give the expected results. The same is true for clinical trials, which again are simply very large experiments. Thus, for example, while it is super exciting to have Geron and ACT proceeding with their Phase I and Phase I/II clinical trials, the odds in a general sense may be against them succeeding at some point prior to final FDA approval to sell the drug. This doesn’t mean they won’t succeed and I sincerely hope they do succeed, but rather what it means is that in the grand scheme of things, most drugs don’t make it.

It is also important to understand that there are key differences between rodents and humans. Preclinical studies in rats and mice are obviously critically important, but how drugs behave in rodents is often quite different than how they behave in humans.

Another challenge for getting stem cell therapies to the clinic is the fact that they are no ordinary drugs. They are not small molecules as is the case with 99+% of all drugs on the market. Rather, they are cells. For each batch, the cells must be grown under the most careful conditions. They must be tested. There will be batch-to-batch variability. Sure, one can say the same thing about small molecule drugs, but those are chemicals that cannot ‘do their own thing’. In theory at least, it is possible to simply make the small chemical drug over and over, but with stem cell drugs, the drugs are literally alive, living cells that can change their programming and theoretically at least go rogue. This makes them far more challenging and expensive to consistently produce and validate.

Finally, the situation with hESC-based drugs such as those being developed by ACT and Geron is highly unique in that there is a very organized and very motivated opposition group to this kind of drug. How often in history have companies had to deal with not only getting their drug through the clinical trial process, but also facing religious opponents of the research behind the drug? Of course I’m talking about the opponents of hESC research. Neither ACT nor Geron rely on federal money to drive their research, but negative publicity about the entire field of hESC research is not helpful and may strongly discourage investment. I understand that ACT’s therapy is based on using a single cell from the human early embryo and technically does not destroy the embryo, but for opponents of hESC research I don’t think that matters.

Crucial in the road ahead is outside support for biotech companies and universities that are developing stem cell-based therapies. Companies such as Geron and ACT may be largely independent of NIH funding, but when they can get it, it is helpful and provides validation of the company that may reassure investors. Funding support and scientific validation from CIRM is also extraordinarily helpful to stem cell based biotechs and university translational programs. Looking ahead, especially with federal uncertainty, the role of CIRM is critical. In addition, I think the investment of CIRM in translational and clinical stem cell research has already paid off and is going to continue to pay off in a big way economically for California in years ahead. In the coming years, we Californians will look back and be proud of our vision to be a leader in stem cell research. Not only a leader in the U.S., but also across the world.

So there may be formidable challenges between stem cell research and stem cell therapy becoming a reality, but that doesn’t mean we shouldn’t try and there are ‘good guys’ like CIRM out there to help fight the good fight. Absolutely we should and we must proceed with this research, as there are millions of patients counting on it.

It is the future of medicine and California and CIRM are leaders in helping make this a reality. But let’s move forward with realistic expectations and some degree of caution. The road ahead will have potholes and maybe even landmines, but if we plan and don’t get ahead of ourselves, then we can navigate the path to success that much more efficiently.