How is the stem cell and regenerative medicine biotech sector doing these days and does recent news about specific biotechs such as Capricor suggest issues for the sector more broadly?
Capricorhad bad news earlier this year related to its stem cells for heart disease kegiatan and things just took a turn for the worse this week as pharma giant J&J severed ties with the small California company (here and here).
Capricor, which has received more than $17 million in CIRM grant funding, could have potentially received hundreds of millions from J&J if the deal had remained intact and if it had met key future milestones.
CEO Linda Marbán, pictured at right, reportedly emphasized the theoretical upside to this development:
“Capricor’s CEO Linda Marbán, Ph.D. accentuated the positive of claiming full rights to CAP-1002, including not only the DMD data but also work with Janssen on developing a commercial-scale manufacturing process for the cell therapy, to which it now has a “fully paid-up nonexclusive license.”
She also said it settled “uncertainty concerning the scope of the license for CAP-1002″ and frees the company to seek partners elsewhere.”
Linda Marban, CEO Capricor
However, this is frankly terrible news for the company. It’s not a plus for CIRM either, which declined to comment when I asked them about it. While the planned new Capricor trial for Duchenne Muscular Dystrophy (DMD) is interesting, it’s a long haul ahead on that front for the company. I reported earlier this year on CIRM’s enthusiasm for Capricor’s DMD trial.
This all leaves me wondering whether in general the use of stem cells for some kind of heart disease will eventually be proven as a new form of cardiac medicine. I hope so. The two articles I cited above about this Capricor and J&J development go much further in their interpretation as they make the argument that the stem cell biotech sector overall is in bad shape and in addition assert that big pharma is losing interest. While that seems overly grim to me, at this moment in time things aren’t exactly very upbeat either in general with a few exceptions.
What stem cell biotech companies in the cardiac area seem most promising to you? What about stem cell biotechs more generally?
Disclosure: I have no financial interests in stem cell biotechs at present.
New FDA Commissioner Dr. Scott Gottlieb, M.D., has in the past touched on stem cells and regenerative medicine therapies in speeches or written comments prior to starting his tenure at the agency. Now that he is Commissioner, he is poised to have direct impact on our field rather quickly and potentially with major changes in store.
How might that unfold?
In one of his first statements that includes stem cells and regenerative medicine as Commissioner, Gottlieb perhaps gave us some hints within a new blog poston the FDA siteentitled, “How FDA Plans to Help Consumers Capitalize on Advances in Science”.
Here is the part of his post related to stem cells and regenerative medicine:
“Our Center for Biologics Evaluation and Research (CBER) is implementing the Regenerative Medicine Advanced Therapy, or RMAT designation. This new process provides another pathway to access FDA’s existing expedited programs, and is available for certain cell therapies, therapeutic tissue engineering products, and certain combination products. The goal of these efforts is to help foster the development and approval of these novel products. We’ve already received almost two dozen requests for RMAT designation and granted four such designations to date. To continue to advance these opportunities, we’ll be announcing this September a comprehensive framework for the development and proper FDA oversight of regenerative medicine. This new policy effort will comprise a series of new guidance documents covering many aspects of the regulation of regenerative medicine products. It will be announced as part of our Innovation Initiative. It will delineate our policies for appropriate and efficient regulatory oversight of regenerative medicine products, in order to demonstrate their safety and effectiveness. It will also create an accessible framework that will enable providers to more easily collaborate on proving these principles for regenerative products that are advanced within local medical institutions. We want to help facilitate these scientific advances, which hold out tremendous potential for treating and even curing diseases. To achieve these goals, we need to make sure that we have a modern regulatory framework in place that can allow innovators to meet the statutory requirements for demonstrating safety and effectiveness.”
Can one read any tea leaves in there?
While we will have to wait until September to get more clarity, this text has some interesting tidbits. The first thing that jumps out at me is the rapid timeline in terms of CBER having new, hopefully clear frameworks by September (that’s only 2 months from now) on specific types of regenerative medicine. I see that as a positive. Second, the concept of an “accessible framework” suggests perhaps the FDA will include guidances (finalized or draft at that time?) that are clear to the public and to a diverse group of stakeholders, and hopefully include concrete examples of various scenarios. For instance, are fat stem cell products like SVF by definition biological drugs? If sometimes not, will that depend on their homologous use? What about non-homologous use of bone marrow products? Where do the amniotic products increasingly popular with clinics fit in here? I could go on probably with 20 questions.
Finally, the last sentence of the quote above has the verb “allow” as pertains to regenerative medicine practitioners, which struck me. The use of that verb suggests a smoother path at the FDA for accelerating investigative stem cell therapies perhaps also with a lower initial hurdle for entry into the FDA review process for investigators and their products. The stakes are big here. I’m very curious to see if the FDA’s new framework on regenerative medicine will hit a sweet spot of promoting innovation while not lowering oversight standards. That’s not an easy task. Whatever the framework, it’d be refreshing if CBER actively enforces its policies on stem cells and regenerative medicine in a prompt, consistent, and clear manner.
My recent poston the push for National Right-To-Try (RTT) including a detailed comment from ISSCR stirred some animated feedback.
In the spirit of encouraging diverse discussion, here I am posting a striking comment I received from a stem cell industry insider regarding that post on RTT as it relates to stem cells and s/he was especially focused on the controversial new Texas stem cell law:
“I understand we disagree about these things, but still a little disappointed in how prominent the “snake oil” salesman scare tactic was. I know it wasn’t you saying these things also, but merely lending your platform. Still; the Texas law is very clear that this can only be accessed after IRB approval AND it has to be a hospital or Medical school IRB. Additionally, the treatment must be administered at that hospital or medical school (state chartered). So it hardly lends itself to the kind of fraud they are talking about. This type of IRB approval and institutional only administration is a greater protection than patients get with FDA APPROVED drugs being prescribed off label. In addition, the criminal penalty for violating the law is clear and enforceable; if you DON”T have the IRB approval and administer it through the hospital or medical school, you can be prosecuted. This is a MUCH more effective tool for going after the frauds than exists without it. I have spoken with DA offices in many states and it’s very difficult to go after these guys. This type of enforcement mechanism is a good step in helping law enforcement; there is no “grey” area.. you either have the med school or you don’t. Texas (not my cup of tea in almost anything else they do) should be praised here for making quantitative steps towards getting the fraud in this area under control; not criticized…”
Some months back there was buzz about the stem cell biotech Longeveron related to its report on early trial data on testing infusions of mesenchymal stem cells for frailty in the aged. Frailty that pops up in some aging folks can manifest in a variety of ways and contribute both to reduced quality of life and mortality.
This week a PR firm for Longeveron sent out an email suggesting that the company’s investigational stem cell therapy might have significance for the flu.
My initial reaction was to be puzzled when someone shared the email with me, not just about the idea, but also the timing. Is this kind of taking advantage of the current worrisome news on the flu? Or a logical attempt to tie in ongoing (albeit very early) clinical research to relevant news of the day? More broadly, what should researchers and biotechs keep in mind in talking about their very early translational and clinical work?
I want to emphasize that Longeveron is doing many things right. They have INDs from the FDA and NIH funding for some work. They are conducting small, placebo controlled trials including a double-blind one. They are publishing their data. Kudos to them.
But this stem cells for flu PR email didn’t sit that well with me. Of course, the flu is on everyone’s mind as it is currently an epidemic in the U.S. with many deaths. Is there a reasonable expectation that Longeveron’s product could help older people not get the flu soon or avoid getting as sick via enhancing response to flu vaccine (and/or reducing frailty)? Is this kind of PR email OK at this stage?
Let’s go through the situation.
First, take a look at that email someone passed along to me from the company’s PR firm:
Subject line “Flu season is bad. Could stem cells make the difference for seniors?”
“…this year’s flu season is predicted to be one of the worst in history, according to medical experts, and one of the hardest hit groups is the elderly. Due to their susceptibility to pneumonia and poor lung function, the older population has a higher mortality rate during influenza outbreaks. So far for the 2017/2018 flu season, the National Center for Health Statistics has received reports of 759 deaths due to influenza and 34,520 related deaths due to pneumonia. Experts are looking to other ways to protect the elderly during severe flu outbreaks.
One therapy under investigation is regenerative stem cell therapy to bolster seniors’ immune systems. The research uses stem cells from 4dukt human donor bone marrow to improve the symptoms associated with aging frailty. Frailty is a syndrome that is marked by a number of symptoms, including poorer lung function and physical performance, higher levels of inflammation and a lower immune system. With frailty, the decrease in immune system defense and lowered lung function, along with less efficacy of vaccines, increases the potential for illness such as the flu to be fatal.
Joshua Hare, M.D., co-founder and Chief Science Officer of biotech company Longeveron, and director of the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine, has been leading the research, and is available for an interview to discuss the research and the promising results. Longeveron and UM have published positive clinical studies of stem cell therapies for aging frailty, for which there is no FDA-approved treatment.
According to Dr. Hare, after the treatment, frail elderly in the trial demonstrated better physical performance and improved lung function, walking an additional 70 meters, for a total of some 400 meters – about the length of a football field.”
The tone is measured so that’s good on that level, but I still have some concerns here.I asked myself, “What’s the data behind this email from the company?” Their research so far is mostly focused on frailty in terms of data and not the flu.
Even on frailty it’s early days. Longeveron’s recent paper entitled “Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial” got some people’s attention. To my eye the data were not that consistent, error bars large, the sample size small, and we need to keep in mind that in this study the higher dose of stem cells didn’t have much effect or none at all (or possibly made things worse) for certain measures associated with aging. There may be reasons for that dosage difference in outcomes but it weakens the case that the stem cells here definitely helped frailty-associated outcomes. For an example of the kind of data from the paper, see Figure 2A here, which relates to lung function.
This kind of mixed bag of data is not unusual for many kinds of early clinical trials and there could be something meaningful going on. This low-high dose split result reminds me of the mixed bag data reported a few months ago from Duke’s cord blood for cerebral palsy trial (see my post).
Tompkins Figure 2A
With these things in mind and noting that the company just started their small study related specifically to stem cells and flu in 2016, in my opinion it is risky to imply in the public domain that there may be any benefit of a still experimental stem cell transplant for the elderly specifically related to flu. Patients may get the wrong idea. Even the addition of one more sentence noting it’s too early to say if there’s going to be any benefit for flu could have helped give the email more balance.
Overall, for the reasons discussed above I am not a big fan of this kind of PR email in the stem cell arena. I’m sure some biotechs would counter that they need enthusiasm and public interest to move forward, but statements to the public and the press on early trials need to be issued with a lot of care…especially during an epidemic.
New FDA Commissioner Dr. Scott Gottlieb, M.D., 
