Stem cell predictions top 20 list for 2016

Stem Cell PredictionsWhat will the new year have in store for stem cells?

2016 promises to have many striking stem cell developments. Below are my top 20 stem cell predictions for what is to come this year in no particular order. Share your stem cell tea leaves in the comments please.

  1. Another stem cell biotech acquisition by pharma (recall Ocata (almost now finally sold) & CDI in 2015).
  2. Charging patients for clinical trial participation, particularly in Japan due to the new policy and here in the US related to predatory clinics, remains a hot topic
  3. Stem cell clinics and doping in sports flares up more
  4. Organoids continue to excite
  5. Bioheart and some other small stem cell companies struggle
  6. Stem cell stocks overall have a bad year
  7. Stem cell clinics ever more aggressively use celeb clients for PR and marketing Why? It is powerful, effective, and essentially free advertising
  8. More news on human-animal chimeras
  9. FDA continues its slow-go approach to action on stem cell clinics/unapproved stem cell products
  10. Pressure from industry and some academics on FDA to not regulate adipose products as drugs and/or to not enforce some other draft guidances including at the upcoming public hearing on the draft guidances
  11. FDA receives increasing public criticism for “slowness” on approving new stem cell therapies including from beyond the stem cell clinic industry
  12. One or more lawsuits against a stem cell clinic
  13. A new stem cell scandal pops up related to publication issues
  14. Some hiccups on mitochondrial transfer/3-person IVF in the UK or China
  15. The trend last year of increasingly blurred lines between legit research entities such as universities and dubious stem cell enterprises continues. This is worrisome.
  16. Stem cell-derived human germ cells stay in the headlines. This has exciting potential for providing new windows into human development and tackling infertility, but also raises thorny issues such as human genetic modification
  17. ViaCyte has some big news
  18. High-profile developments on veterinary use of stem cells
  19. Animal cloning, particularly in China, continues to proliferate
  20. More rumblings on possible human reproductive cloning attempts

Disclaimer: This post is not meant as financial advice. Consult an expert before making financial decisions.

Muddier stem cell waters: Stemedica teams up with UCSD doc?

stemedicaAn increasing trend in the stem cell arena is the teaming up of clinical partners with very different backgrounds and priorities. For instance, academic institutions are more often working together with for-profit stem cell clinics.

Another branch of this larger trend is the observation that some publicly traded stem cell biotechs such as Bioheart are increasingly turning to non-traditional means of raising cash such as through dubious stem cell training for doctors or other unexpected ventures.

It seems that in the past things were clearer in terms of who is compliant and who isn’t, who is following the spirit of FDA regs and who isn’t, and so forth.

The waters of the stem cell world are getting far muddier today as I predicted in my top 20 predictions for stem cells in 2015.

It’s a somewhat radioactive topic.

Why?

On the one hand such team efforts between academic and industry could be beneficial by speeding translation to patients, which is what the field needs. Cheers for that.

However, on the other hand for-profit stem cell clinics and academics do not always see eye to eye on how to do things, how to report findings, bioethics, patient consent, stem cell tourism, the proper way to handle public relations, and such.

Increasingly the commercialization of stem cells is making for strange bedfellows.

A good recent example is the work just announced that Stemedica indicates links it with UC San Diego (UC) for a stem cell trial for Alzheimer’s Disease:

“The study is sponsored by Stemedica International, S.A. and will start at the University of California, San Diego (UCSD) under Principle Investigator Douglas Galasko, M.D. and expand to other sites.”

You may recall Stemedica from the media frenzy over the last half a year on their role in the treatment of hockey legend Gordie Howe for stroke. In fact, Howe reportedly just got a second treatment from Stemedica and its partner Novastem in Mexico.

I found some aspects of the whole Howe-Stemedica story to be of great concern. For example, there is some question over whether the free treatment of Howe has led to stem cell tourism via more patients traveling to Mexico for non-FDA approved interventions. Football great Bart Starr may also have recently gotten such a treatment via Stemedica as well.

Of this new Alzheimer’s trial, Stemedica says in a PR:

“This study was approved based on the excellent safety profile of Stemedica’s cGMP-manufactured, hypoxically-grown stem cells and on solid pre-clinical data obtained by Stemedica International in cooperation with the École Polytechnique Fédérale de Lausanne of Switzerland and with a grant from the Swiss government,” said Lev Verkh, Ph.D. Stemedica’s Chief Regulatory & Clinical Development Officer. He continued “We are very proud of Stemedica’s clinical program under U.S. INDs for several indications including ischemic stroke, acute myocardial infarction, chronic heart failure, cutaneous photoaging and Alzheimer’s disease. At the study’s conclusion we will understand if our approach is efficacious versus placebo in subjects with Alzheimer’s-related dementia, as evidenced by neurologic, functional, and psychiatric endpoints.”

Now in principle some definite good could come from Stemedica working with academics and notably they have an FDA-approved IND for this, which is great. At the same time there may well be different priorities at work. I guess we’ll have to wait and see how it goes.

Other stem cell clinics raise more concerns and claim university affiliations too. For example, earlier this year we saw an odd stem cell clinic with their NIH-like name (National Institutes of Regenerative Medicine; NIRM) turn out to be affiliated with Cell Surgical Network, the largest chain of stem cell clinics in the US, which sells non-FDA approved “therapies”. NIRM had claimed a UCSD affiliation as well, but I no longer see that apparent on their website today.

Notably, Stemedica is different in some key ways from the dubious stem cell clinics we often talk about. They have a growing number of FDA-approved INDs and by all accounts I’ve heard through the grapevine that the stem cells that Stemedica produces are cGMP quality. Still their actions have raised concerns on some levels and the promotion of stem cell tourism to Mexico is a worry.

Overall, as the stem cell waters continue to muddy and with essentially zero apparent regulatory action by the FDA’s CBER specifically on stem cell clinics more broadly in the last couple years, I predict it will be increasingly difficult to know what is going on with any particular stem cell offering. Instead of getting clearer, things are getting grayer.

Bioheart on the edge in 2015?

Bioheart logoStem cell biotech company Bioheart ($BHRT) has had a rough 2015 so far.

Could this year be a decisive, negative tipping point for the company?

It has a number of clinical trials going, but from my view things seem increasingly uncertain.

An oddity amongst stem cell biotechs, Bioheart and its leadership have at times seemed to toy with what some might view as controversial projects. Kristin Comella, CSO of Bioheart, has played a major role in other ventures including in the past with the Ageless Institute, a stem cell clinic. Earlier this year, investors reportedly including Brenda Leonhardt (ex-wife of Bioheart founder, Howard Leonhardt) filed a lawsuit against Bioheart for millions in alleged unpaid debt.

Comella and Bioheart are also involved in what I view as concerning training of physicians in the use of a fat-based stem cell product that might be an unapproved biological drug from the FDA’s perspective. Comella provided some insights on Bioheart and the doctor stem cell training in a recent interview I did with her. She didn’t seem concerned with the FDA.

Bioheart has another puzzling venture, US Stem Cell Clinic, LLC, (“SCC”), which it describes in this way:

“a partially owned investment of Bioheart, Inc., is a physician run regenerative medicine / cell therapy clinic providing cellular treatments for patients afflicted with neurological, autoimmune, orthopedic and degenerative diseases. SCC is operating in compliance with the FDA 1271s which allow for same day medical procedures to be considered the practice of medicine. We isolate stem cells from bone marrow and adipose tissue and also utilize platelet rich plasma.”

Recent FDA draft guidances at the very least call into some doubt the compliance of some of the offerings of US Stem Cell Clinic, LLC. The FDA could back down on the requirement for the fat-based stem cell product SVF to be approved in advance as a biological drug, but then again it might not.

Investors seemed worried. Bioheart stock has taken a beating recently, down almost 60% in the last 3 months and almost 7% just today. Overall it seems that something has got to give soon.

Disclosure: I own no stock in Bioheart or its direct competitors. This piece is not financial advice.

Interview with Bioheart CSO, Kristin Comella: trial update, MD stem cell training & FDA

Kristin ComellaI invited the Chief Scientific Officer (CSO) of Bioheart, Kristin Comella, to do an interview after hearing some buzz that this could be a critical time for the company and that it might have been recently visited by the FDA.

Note that Comella not just Bioheart CSO, but also the primary instructor for physician training in stem cell methods offered by the company US Stem Cell Training.

Can you update us on how Bioheart is doing with its clinical trials/INDs?

Comella: Our completed clinical trials of MyoCell to date have been primarily targeted to patients with severe, chronic damage to the heart who are in Class II or Class III heart failure according to the New York Heart Association, or NYHA, heart failure classification system. We have completed various clinical trials for MyoCell including the SEISMIC Trial, a 40­patient, randomized, multicenter, controlled, Phase II­a study conducted in Europe and the MYOHEART Trial, a 20­patient, multicenter, Phase I dose­escalation trial conducted in the United States. We were approved by the FDA, to proceed with a 330­patient, multicenter Phase II/III trial of MyoCell in North America and Europe, or the “MARVEL Trial”. Thus far, 20 patients, including 6 control patients, have been treated. Initial results for the 20 patients were released at the Heart Failure Society of American meeting, showing a significant (35%) improvement in the 6 minute walk for those patients who were treated, and no improvement for those who received a placebo. On the basis of these results, we have applied for and received approval from the FDA to reduce the number of additional patients in the trial to 134, for a total of 154 patients. The SEISMIC, MYOHEART, and MARVEL Trials have been designed to test the safety and efficacy of MyoCell in treating patients with severe, chronic damage to the heart.

In addition, we  received approval from the FDA to conduct a Phase I safety study on 15 patients of a combined therapy (MyoCell with SDF­1) called the REGEN trial. Advancement of the MyoCell and MyoCell SDF­1 clinical development programs is contingent, among many factors, upon the Company obtaining access to sufficient funding to execute the necessary clinical trials to achieve proof of efficacy and regulatory authorization to market such products.

Bioheart has spent over $125 million researching cellular therapies for patients and supporting clinical trials. We are committed to bringing more treatments forward and all revenue that is brought into the company is put towards advancing this science. Our FDA phase 3 MARVEL Trial for congestive heart failure patients is budgeted to cost $10 million dollars for 100 patients. Trying to complete double blind placebo controlled trials is very expensive and there is limited funding for companies who are trying to complete these trials.

How did you and Bioheart get interested in stem cell training courses for MDs? Is US Stem Cell Training owned by Bioheart? Is there some common ground between the missions of the two?

Comella: We are currently offering courses for physicians through US Stem Cell Training which is a wholly owned subsidiary of Bioheart. The field of regenerative medicine is expanding very rapidly and physicians may not have adequate exposure to these topics during medical school. Our goal is to provide physicians with the latest research in cellular medicine. The course includes didactic lecture and hands on demonstration with topics including:

  • Stem Cell Biology
  • Embryonic Cells
  • Induced Pluripotent Stem Cells
  • Bone Marrow Stem Cells
  • Adipose Stem Cells
  • Platelet Rich Plasma
  • GMP Training
  • Regulatory Environment
  • Fat Harvesting Procedure
  • Bone marrow isolation Procedure

The course is constantly updated with new research and data as more studies are published. The goal is to familiarize physicians with the latest research and how this may affect their practice. We also host a monthly webinar series which includes journal clubs and guest lecturers. This field is growing and we want to provide physicians an opportunity to learn more about regenerative medicine. Many patients are asking their physicians questions about regenerative medicine and our hope is to bridge the gap between basic research and clinical practice.

What are your views on the recent FDA draft guidances including on adipose in which the FDA suggested that SVF is a biological drug?

Comella: The FDA has recently released a draft guidance document regarding the use of human cell and tissue products used during the same surgical procedure from adipose tissue and has requested comments from the public on this guidance. Please note that guidance documents represent the FDA’s “current thinking on the scope” of the topic. “FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the FDA’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA’s guidances means that something is suggested or recommended, but not required.”

We do not believe that the current draft guidance document will affect our ability to offer in-clinic cell therapy from fat to our patients. We understand that the FDA’s draft document has elicited much resistance from the public and highly respected organizations such as AABB Center for Cellular Therapies and The Academy of Regenerative Medicine have voiced their opposition.

It is impossible to predict what the FDA will do regarding any in clinic therapies so I can only tell you what has happened in the past. In December of 2014, the FDA visited our lab as well as three physicians who are doing SVF procedures. The FDA took no action against anyone and did not stop the SVF procedures. Many of you have seen that these procedures can provide benefit to patients who have failed other therapies. Our primary goal has been and will continue to be safety and well-being for our patients.

Oftentimes, emerging technologies are met with skepticism and criticism. When stents were first introduced as an option for patients having a heart attack, many famous cardiologists criticized them because of the risk of restenosis (blockage). Yet stenting is now a common cardiac procedure. Cellular medicine has existed since the 1960s and is commonly used for cancer patients under the term Bone Marrow Transplant. These treatments were never put through double blind placebo controlled trials; nevertheless, we accept them as the standard of care. In addition, cellular medicine for degenerative diseases has been the subject of thousands of animal studies and clinical trials. Many of these studies date back to the 1980s. I think a fair question to ask a patient who has failed to benefit from traditional medicines and therapies is “how many studies would you like to see before you try to harness your body’s own healing potential”. Most patients are willing to try something experimental and, provided that companies are clear on the possible risks versus rewards, these therapies should not be withheld from the public.

I think that the body’s natural healing mechanisms are fascinating. The ability to harness this natural healing potential to reverse the effects of degenerative diseases or injuries is very powerful. We have a lot to learn about regenerative medicine but we are now starting to realize the potential by bringing these therapies to clinic. With any new therapies, there are challenges to bringing them to market. In addition, it is difficult to navigate the regulatory environment because these therapies are unlike any others currently available to patients. Cellular therapies should not be regulated in the same way as drugs and devices and many regulatory bodies are trying to establish new rules and guidelines. I am not sure that a person’s own cells should be regulated in the same way as a drug that is manufactured. It is important to advance science with patient safety as the primary interest. We have treated patients whose lives have completely changed for the better because of regenerative medicine and this is why I love this field!

Was US Stem Cell Training or Bioheart recently visited by the FDA? If so, how did the visit go and could you please provide a copy of the 483 form?

Comella: In December of 2014, we had an unannounced inspection from the FDA of our lab as well as three physicians who are doing SVF procedures. The FDA requested copies of our protocols and information about all of the materials that are utilized in the SVF process. They also specifically requested information regarding several IRB protocols. The FDA toured our lab facilities as well as the facilities of three different physicians. The FDA took no action against anyone and did not stop the SVF procedures. No warning letters (i.e. 483s) were issued. We received notice that all the documents were sent to CBER who reviewed and at this time they have no additional questions. Therefore the investigation was closed. Please note that this is the second investigation for Bioheart and we have not received any warning letters (483s). Our lab is a registered FDA tissue bank (FEI: 3005825762) and we are subject to unannounced FDA inspections.