Burt Northwestern Stem Cell MS Trial Part 2: Marketing ‘Cure’-Like Outcomes?

Can science now cure MS in some patients with stem cells or is that near on the horizon? What about stem cells for other serious autoimmune disorders? What are the risks to patients in terms of health, money, and hope? What if patients must find $100,000 or $200,000 just to get into a clinical trial for this and insurance only sometimes helps in a big way? Will the trial conclude with an approved product that works and is safe enough? It’s always complicated with an ongoing clinical trial to make predictions.

Today’s post is Part 2 of a three-part series on the Dr. Richard Burt stem cell trials including for MS at Northwestern. You can read Part 1 here where I discussed the big picture of the trial, costs and ethical as well as practical issues, and Part 3 here. The point of this blog series is to start an open, diverse discussion and exchange of information about this unusual kind of clinical trial. In Part 2, I focus here on the apparent marketing of the trial.

This NW team has made headlines with exciting, novel approaches to autoimmune disease using stem cells for more than a decade including MS. As a stem cell scientist myself, I believe there is real potential here and hope that the trial is successful in the end. While there currently is no approved stem cell therapy for MS, patients understandably have high hopes including for the MS trial and you see these hopes articulated by the patients on the web.

‘I don’t use the word cure, but…’

Overall, what exactly do patients expect specifically from the Northwestern stem cell trials for MS and other conditions? In these Northwestern trials are many patients expecting cures or at least life-changing outcomes? My sense is that the answer is often “yes” based on all the comments and feedback I’ve gotten from patients and what I’ve read online, while other patients have more moderate expectations. After Part 1 of this series some patients already enrolled in the trial told me they believed they had their life changed by the clinical trial investigational therapy. It feels as though some patients perceive themselves as cured.

A different, but also very important question follows: are patients actively led to believe they will get cures or outcomes similar to cures by the language used by Northwestern? I’m not sure, but let’s take a look at answering that question.

A few quick Google searches and you can find an assortment of information about the NW trials including videos. For instance, you can see a video above with statements from Dr. Burt, those he works with, and patient testimonials about experimental stem cell treatments in clinical trials that he is testing for a variety of conditions. It’s a surprisingly glitzy marketing video and I believe not sufficiently cautious about avoiding giving patients too much hope from a clinical trial. Richard Burt Stem Cell VideoIn fact, the video, its music, the cool flashing lights, and the words spoken make for a very aspirational experience, but what about science and medicine? Data?

The flashy video also makes specific, perhaps still as yet unproven medical claims. Most dramatically, the video claims “a completely normal life not using medications” (see screenshot) is possible from the trial, a phrase that Dr. Burt also says in the video.

This big claim is probably going to be equal to a cure in the minds of many patients and such a statement may be hard to resist for those suffering. As I’ve communicated with patients with severe MS, I’ve tried to imagine myself in their shoes (some even asked me to do that) and in that hypothetical scenario a claim of “a completely normal life not using medications” would be like a magnet for me to that clinical trial, especially if I felt that standard chemical medications weren’t doing the job or had bad side effects. I’d interpret that phrase as meaning a cure or cure-like outcome being available if I were an MS patient.

But I’m not an MS patient and I don’t claim to have great insight there. I’m a skeptical scientist who has seen stem cells over-sold too many times over the years in general even as I wish for proven new stem cell therapies to come on the stage. If I had to predict, I would be optimistic that several stem cell therapies will be approved in the next decade, but where we are at today is more complicated. In part for that reason, in my view a “completely normal life” kind of statement is a questionable way of describing a still investigational stem cell therapy that may ultimately not be proven to be safe and effective for widespread use or that might work only temporarily or only work in a subset of patients.

Also included in that same video is an apparent trial patient specifically saying “I am cured” and in that context the patient is kind of like a spokesperson for the institution. Speaking of cures, on the now password-protected Northwestern stem cell immunotherapy website, which although external to the official Northwestern University web domain has its logo at the top, “Curing multiple sclerosis” jumps out at the visitor to the site right there in the middle of the page. It’s there without even a question mark in the form of an image from an article in The Economist about Burt’s work.  As I mentioned in Part 1 of this series, the magazine is responsible for its own title choice for an article, but why include that on a page for patients about your ongoing clinical trials? At the top left of the page a header says unequivocally, “stem cell therapies are changing lives”, which also suggests big success.

stem cells MS Northwestern University

Is all of this sufficiently cautious so as not to give patients who are considering enrolling the wrong ideas about where things stand? While I’m not a clinical trial expert, when I see an ongoing trial making bold claims it raises concerns. I don’t have direct experience with the team and as I said in Part 1, the NW folks seem unwilling to have a dialogue on this. Note that some patients have indicated to me that the Burt team does not mention a cure in person as they talk with patients and those patients view the NW team as appropriately cautious so that’s important to keep in mind for balance.

The state of the clinical science including research publications

An important caveat here is that maybe the Burt team has amazing preliminary trial data that has convinced them that they can back up big claims, but if so to my knowledge that data is not published. If that data exists it should be peer reviewed and published before big claims are made publicly that patients will see. For reference, see the 2016 ISSCR stem cell guidelines that provide a helpful framework on stem cell clinical studies.

What about already published papers that might support what Burt’s team is doing? Over the years Burt has published important, novel papers on his team’s experimental stem cell transplants for MS (and other autoimmune conditions including Type I diabetes) and some gave encouraging signs of short-term improvements. I think it is fair to say he’s a leader in his field. However, the publications do not contain conclusive results and as best as I could see the data in those papers on MS are not from RCTs. Hopefully new papers with additional data will be published soon that clarify where the MS trial stands more recently.

The past Type I diabetes stem cell clinical trial work from Burt’s team is worth a look for comparison to what is going on now with the MS trial and how it is characterized.

In 2007-2010 Burt’s research made a splash of a possible revolutionary, stem cell-based approach for Type 1 diabetes from work done with pediatric patients along with a team in Brazil collaborating with Dr. Julio Voltarelli. He said back then too that he doesn’t use the word cure, but there seemed to be pubic indications of at least dramatic changes for the better in patients. There seemed to be major science hype by the media itself about this. For instance watch the ABC News video above. Also, take a look at this quote from a Time Magazine piece:

“I wouldn’t use the word cure,” says Dr. Richard Burt, one of the co-authors from Northwestern University. “But it appears we changed the natural history of the disease. It’s the first therapy for patients that leaves them treatment-free — no insulin, no immune suppression for almost five years.”

Exciting, perhaps history-making work 10 years ago using a stem cell transplant with partial immune ablation for an autoimmune condition in the form Type 1 diabetes?

Whatever happened to this line of diabetes stem cell diabetes research? I don’t know. Their 2007 and 2009 JAMA papers were exciting, but after that I can’t find anything other than a withdrawn trial clinicaltrials.gov listing. If anybody is aware of what might have led to the possible end of or long-term pause on that line of research please let us know in the comments.

Again, I hope the ongoing MS trial is proven in the end to be a success because so many desperately ill people would be helped, but again clinical trials are tricky things to predict and often do not turn out as people hope. Science is more generally that way too and we have to see what the data teach us and what our peers think of the data and their views of our interpretations of the data.

Overall, there are many potential risks associated with elevated patient expectations for an ongoing clinical trial and associated marketing, and these issues are only magnified by requiring patients to pay large sums of money for access to a trial. In Part 3 of this series I discuss additional issues including funding, the future, and patient perspectives.

Recommended weekend reading on stem cells & science

I try to catch up on my science reading over the weekends and evenings. Here’s my recommended weekend reading on stem cells & science.

Did I miss anything especially cool? Let me know in the comments.

Direct reprogramming of skin cells into insulin-producing cells. I love direct reprogramming.

Healios and Athersys Enter Into Regenerative Medicine Partnership. Can they together create regen med success?

National honor for helping “the blind see” comes from CIRM blog.

human animal chimeras

Fun piece on CRISPR language by Ben Zimmer. ‘Crispr’ Breaks Out Of the Lab. If you don’t know what a backronym is, you should be interested in learning more.

Big claims here for zero off targets for a next gen CRISPR system. Zero is a very small number, eh?

The gut microbiome of the 5,000 year old frozen dude turn out to be a goldmine of sorts of info. Nice piece by Carl Zimmer, Ben’s brother. OK, what did these two brothers who are unusually great writers eat while growing up? Wheaties? 

George Church on The Late Show with Stephen Colbert. Wonder what Letterman would think of George’s Top 10 List for genes with interesting phenotypes in humans? See my interview with Church for that list and a lot more interesting perspectives.

Human-animal chimeras, Antonio Regalado, tells us in a nifty article are currently gestating on farms (image above from that piece).

Ed Yong writes that CRISPR’s most exciting applications are in gene transcriptional regulation (admittedly a cool area) rather than in genetic modification. Great piece, but I disagree with the superlative.

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.

New biotech Semma Therapeutics joins ViaCyte & Betalogics in stem cell Diabetes arena

Semma Therapeutics

Semma’s technology director Felicia Pagliuca, with CEO Robert Millman. Boston Globe Picture

A new biotech startup, Semma Therapeutics, announced that it seeks to fight diabetes via translating technology from the lab of Doug Melton at Harvard to the clinic.

Another major player in cell therapy-based arena for Diabetes is most likely good news for patients.

Quoted in the Boston Globe, there is a good deal of enthusiasm about the potential of this kind of therapeutic approach:

“This would be a huge breakthrough,” said Dr. George L. King, a Harvard Medical School professor and research director at Joslin Diabetes Center. “It could cure diabetes.”

Semma TherapeuticsSemma will have to compete with ViaCyte and Betalogics, which could prove challenging given, for example, that ViaCyte already has an ongoing FDA-approved clinical trial. Still Semma has raised more than $40 million, which is a good start, and this capital came from some known bio-investment players:

“Sensing a business opportunity at the juncture of stem cells and diabetes, venture firms MPM Capital, Fidelity Biosciences of Cambridge, and Arch Venture Partners of Chicago are teaming with Minneapolis-based medical technology giant Medtronic plc to back Semma in the company’s first round of financing.”

Two of the leaders of Semma are former Melton lab postdoc Felicia Pagliuca, and CEO Robert Millman. Pagliuca was first author on a high-profile Melton lab paper in Cell published just about half a year ago and post-pub reviewed on this blog.

The Semma website has more information.

Why the name Semma?

I’m not sure.

There is a SEMMA acronym in high-tech:

Sample, Explore, Modify, Model, Assess.

It’ll be exciting to see how Semma performs and more broadly how cell therapy-based approaches to Diabetes evolve. I view Semma coming on the scene as a positive.

Viacyte & Mesoblast present at CIRM Meeting

Allan Robins ViacyteAllan Robins of Viacyte (pictured at left–sorry for the fuzzy image) and Paul Simmons of Mesoblast presented this morning at the CIRM Grantee Meeting.

Both talks were outstanding.

Robins went first. He started by saying how Viacyte had a productive pre-IND meeting with the FDA last year.

I believe a target for them is to have IND in Q1 of 2014 and hopefully move to the clinical trials soon after.

I gotta say I love Viacyte’s technology. Having a frozen product that then can be recovered in culture for 3 days before loading into the capsule seems like a big plus.

Simmons also gave an interesting talk on Mesoblast’s status. Quite impressive.

I find it astounding just how big their pipeline is. They have perhaps as many as 10 products. They also have an impressive number of trials already ongoing based on allogeneic off-the-shelf products based on mesenchymal progenitor cells (MPCs).

Simmons posed a hypothetical question that people sometimes ask the company related to trophic factors made by MPCs, “Why don’t you just use the trophic factors that are secreted as the therapy”. Simmons’ reply was both humorous and encouraging, “These cells are quite intelligent!”

MPCs secrete just the right combo of factors as instructed by a given environment.

Both talks were great and I think these companies have strong potential to help thousands of patients within a decade.

Disclosure: I am not an investor in either company nor currently any company in the stem cell field.