First impressions of the US stem cell environment from an Aussie

Heather_MainBy Heather Main

I moved to the San Diego from Australia in August 2015, and Paul asked me if I could write something on my first impressions of doing science in the US, as opposed to other countries I have worked/studied in (Australia, Scotland, Sweden and Singapore).

If you look at the land size of Australia and consider that we have only 7% of the US population you will understand directly that funding and collaborative opportunities are not as easy to find. There’s probably little collaborative advantage in the US compared to Europe, which has over double the number of people as the US and only 3% larger land mass. In defense of Australia we punch above our weight, with the first stem cell company (Stem Cell Sciences) and currently the world’s largest (Mesoblast) originating there…even Viacyte has Australian origins.

It seems like it is hard not to be political here in the US….I guess I have arrived at a special time, but after working in Sweden for 5 years and living through gun control regulation following the 1996 Port Arthur massacre in Australia, I don’t understand the opposition to publicly funded healthcare, how a regarded education is ‘purchased’ and the 17th century resistance to gun control regulation. …I guess you need to be born into it. I think the political minorities have almost as much backing in Australia but are not as extreme and have less volume, so the international effects are minimised.

Relevant to stem cell research, the Colorado Springs Planned Parenthood shooting in November 2015, made me wonder how extreme the fight to protect the rights of a fertilised egg still is. My only explanation for these people is a 16th century belief in a ‘homunculus’ (fully formed miniature human present in every sperm)…Someone please get them a microscope.

homunculus

Above. The : A 16th century theory for human development. Obviously not real though but an image that seems to exist in the mind of the anti-choice movement

All of this seems contradictory to a country with arguably the most advanced thinking and technologies but I was pleased to see the numbers don’t support it with;

– 2008 Bush allocation of $88 million in NIH funds to human embryonic stem cell research (compared to $381 million to adult stem cell research)

– 2014 Obama allocation of $166 million, while non-embryonic only slightly increased ($443 million), with a large allocation to iPSC projects.

This even indicates the recognised importance of pluripotent technologies over adult somatic technologies.

I wonder though if this balance is also recognised in the public and adult somatic cell spaces. In an effort to sell an alternative to hESC, the potential of adult somatic stem cells was drastically inflated. Recently I have attended a number of adult somatic stem cell talks who describe the expression of Oct4/nanog etc. in their population of choice, even call them pluripotent….though I am yet to see the teratoma/PluriTest, or clinical trial for functional long term grafting behaviour. Literally hundreds of clinical trials on MSCs have been done over the last 15 years so I guess if the data were there, we would have seen it.

MSC clinical trials

Number of registered clinical trials of mesenchymal stem cells-based therapy on ClinicalTrials.gov.

My fears were allayed when reading Don Reed’s book, in which he interviews fantastic adult stem cell researcher and patient advocate, Dr Jan Nolta. When asked if injection of mesenchymal stem cells was a possible cure for Huntington’s Disease, she answered straight out “No,…..But it buys us time”. Herself and Dr Vickie Wheelock agreed that hESC or hiPSC would be needed for the actual cure. It’s refreshing to see this honesty, a recognition that we need to work together, promote both sides, but realise the timelines of expected contribution from each. Saying it is not a cure does not mean it is not important.

So far I have enjoyed a range of meetings, including both Stem Cells on the Mesa and the World Stem Cell Summit on US soil and look forward to ISSCR in June. Unfortunately from Australia it is wildly expensive and time-consuming to travel to all of these meetings….you can fly LAX to Sydney in 15 hours as opposed to the 12 hours it took my husband to get from San Diego to Florida….

Australia US map

Good or bad I think the US is a place where anyone with a decent backing can make changes with great relevance on the International scale. If you can legalise hESC research under a Republican government, you can do anything!

Stem cell treatment cost 2.0: legit therapy

stem cells costWe hear so much about exciting potential stem cell therapies. Some of these are rigorously evaluated ones in the FDA clinical trial pipeline and others are available right now mainly through predatory stem cell clinics. Earlier this year I posted about the cost of the offerings of dubious stem cell clinics.

In this post, I address the cost of a future, legitimate, FDA-approved stem cell therapy. How high will that be?

This is a critical question because if many patients cannot afford a stem cell therapy then the impact of that therapy is reduced. Cost is inversely related to access. On the other hand, stem cell biotechs must make some profit or they will go out of business. Investors, who are often enthusiastic boosters of the stem cell field, will lose large sums of money and confidence in the field too in that scenario if stem cell treatments are priced “too low”. What is the “right” price?

There is likely to be increasing pressure on biologics drug prices as well from the federal government. Witness Hillary Clinton’s recent tweet on this topic below that sent people into a tizzy.

At the state level, such as here in California, the question of stem cell treatment cost is also becoming more pressing including for our state stem cell agency, CIRM. As CIRM-funded clinical trials advance, which is a wonderful thing, at the same time we get closer to where someone will have to decide on stem cell price tags.

We can look at what other cellular drugs have cost as guidance for the price tag range for stem cell treatments. For instance, Prochymal (its old name under Osiris) that is now rebranded as TEMCELL from Mesoblast/JCR likely will cost about $200K for a full treatment for GVHD (HT to Alexey). Provenge, the cellular prostate cancer drug from the controversial biotech Dendreon had (has?) a price tag of $93K. The most expensive drug in history, the gene therapy med Glybera will cost around $1.5 million per patient.

Realistically, a typical legit stem cell therapy could easily be $100K per patient. A personalized cellular medicine such as an autologous stem cell-based therapy could easily run into the hundreds of thousands per patient. Some therapies could go as high as $500,000 (see this helpful piece by David Jensen) or even into the millions.

Irv Arons

Irv Arons (@iarons) has come up with a great table of cost estimates focused in the area of vision therapy (free registration required). Thanks to Irv for permission to use it here (above).

How will patients afford such expensive therapies?

Will such therapies be covered by governmental agencies or insurance companies? They should.

We should also be keeping in mind the current costs of treating today’s patients with major and sometimes chronic diseases. These costs run into the hundreds of billions or above a trillion dollars each year in the US alone. That’s important context and rightly indicates that the costs of stem cell therapies to society may be appropriate even if at an individual level they seem high.

How does this compare to stem cell treatments at predatory clinics?

Such “treatments” range from $5,000-$20,000 each and most patients with whom I have talked either received or were pitched at least two such treatments, amplifying the total cost. The cost to the clinic of the treatment itself can be as low as $500-$1,000. Some clinics claim to have treated thousands of patients suggesting they are making millions in profits.

Why are stem cell clinic offerings typically relatively cheaper than legit treatments? Frankly, it is because they don’t follow the rules or do the necessary studies to prove safety and efficacy. Ten thousand dollars is still a lot to pay for something that doesn’t work and could even be harmful.

Even so some consumers may perceive dubious stem cell treatments as the way to go because of the lower cost, particularly if the legitimate stem cell field fails to do a good job at educational outreach and the FDA continues to effectively do nothing about the stem cell clinic problem.

The bottom line remains a question. Where’s the stem cell price sweet spot where we can help the most patients, but also generate a needed profit for the biotechs?

We need to find an answer to this question soon.

What is the top stem cell biotech of 2014? Take our poll

What is the most exciting, important, promising, all-around awesome stem cell biotech of 2014? Vote and tell us why in the comments.

Book Excerpt: Top 4 Stem Cell For-Profit Good Citizen Biotechs

The below is an excerpt from my book, Stem Cells: An Insider’s Guide.

I hope you enjoy this excerpt and the book, which I think is a really good deal at under $27 paperback or under $17 for E-book version.

Having our innovation and ethics too

In the stem cell field you can have it both ways. As a company, you can be ethical and help patients. There are many examples of stem cell-related corporations doing “the right thing” when it comes to developing therapies based on growing stem cells in the lab. Below I discuss a few of these companies (Disclosure: I have no financial interests in these companies, which are listed in alphabetical order).

Advanced Cell Technology

As one example, let me mention a company called “Advanced Cell Technology” or ACT. I would argue that, especially in the last half dozen or so years, the company has been a model citizen in the for-profit stem cell field.ACTC

ACT’s most advanced product in the pipeline toward the clinic is an embryonic stem cell-based therapy for macular degeneration, the leading cause of blindness. ACT grows the embryonic stem cells in culture and differentiates them through a complex process into special cells called retinal pigmented epithelial cells (RPEs). Macular degeneration robs people of their sight because their endogenous RPEs die off. Therefore, the principle behind ACT’s therapy is to replace the endogenous RPEs with exogenous ones. So far, ACT has reported no major negative outcomes from its trials of transplants of embryonic stem cell produced-RPE. I am discussing ACT here because it follows FDA rules and works in an ethical manner to protect patients. It publishes its data and engages patients.

Athersys

Athersys is an adult stem cell company developing allogeneic products to treat a number of important human diseases. The company has five clinical trials listed in the government database. AthersysThe target diseases include stroke, heart attack, blood cancers, obesity, and ulcerative colitis. Their top-line product, MultiStem, is described by the company in one of their clinical trial write-ups as follows:

“MultiStem(r) is a new biological product, manufactured from human stem cells obtained from adult bone marrow or other nonembryonic tissue sources. Factors expressed by MultiStem cells are believed to reduce inflammation and regulate immune system function, protect damaged or injured cells and tissue, promote formation of new blood vessels, and augment tissue repair and healing.”

Athersys has a good reputation in the stem cell field for transparency including regularly publishing their data and following FDA regulations.

Mesoblast

Mesoblast is another good citizen in the stem cell field and has an unusually large number of stem cell products in the pipeline. Their work is based on a type of cell that they call the “Mesenchymal Progenitor Cell” or MPC. Interestingly, while typically progenitor cells have less potency than stem cells, as we discussed earlier in this book, Mesoblast’s MPCs are not your ordinary progenitor cells. 

Mesoblast_Ltd

I recently heard a talk by Dr. Paul Simmons of Mesoblast who reported that MPCs are in fact more potent than MSCs, which is an interesting paradox of nomenclature. Mesoblast is conducting FDA-approved clinical trials for a host of human diseases. I found 9 clinical trials listed for Mesoblast including for conditions as variable as spinal disc injury and heart attacks.

NeuralStem

NeuralStem is a fourth good citizen in the stem cell for-profit world. They are a model citizen for the field when it comes to transparency says Alexey, who I trust on this a great deal, publishing data and even publicly releasing their patient consent form, a rarity in the stem cell field. NeuralStem currently has four clinical trials listed in the database: two on depression, one on spinal cord injury, and one on Amyotrophic Lateral Sclerosis (ALS; Lou Gehrig’s Disease).NeuralStem

The key, positive roles of investors in good-citizen companies

It is important to also highlight the crucial role of investors in making safe, effective, ethical, and compliant stem cell treatments a reality. For-profit stem cell companies including the good citizens of the corporate stem cell world need large amounts of cash to make stem cell-based medicine a reality.

The money comes from investors, who are hoping that some of the exciting stem cell biotech companies become profitable. I know from talking with many of the investors that they are choosing to invest in the stem cell companies not just because they believe that they will be profitable, but also because the stem cell products of those companies will potentially help people suffering from diseases and injuries. I believe that the investors in publicly traded stem cell companies fulfill a key role in accelerating stem cell cures. They tend to be a highly educated, engaged group of people as evidenced by their posts on a website for stem cell investors where I sometimes blog as well.

Investors in privately owned companies can also have positive roles, but I am concerned that in that context the lack of transparency may lead to a more complex, potentially ethically problematic influence.

The main overall challenge in a for-profit setting is to create a business regulatory environment in the stem cell field that enables good actors to succeed.

Stem Cell & Cell Med Industry Briefs

Mesoblast_LtdWhere do things stand with some players in the for-profit world of stem cell and cellular medicine companies? Here are a few brief news items with quick analysis. Mesoblast is dominating the news of late.

Mesoblast reported good news from its Phase II safety trial for its mesenchymal progenitor cell (MPC) product in patients with Type II Diabetes. There were no treatment-related adverse outcomes and as a bonus there were hints of efficacy.

Osiris Going in New Direction. Cellular medicine company Osiris has been in the news quite a lot lately. The latest is that CEO & President Randall Mills is stepping down after about 10 years as the company’s leader. Personal reasons were cited, but the move could reflect a change in direction for the company. About a month ago we all learned that Osiris had received an untitled letter from the FDA and a few weeks before that it sold off its stem cell portfolio to Mesoblast.

Celgene Partners with OncoMed on the cancer stem cell front. In a case of one plus one is probably more than two, Celgene shelled out big bucks to partner with cancer stem cell biotech OncoMed to team up against cancer stem cells. OncoMed has been on a roller coaster since its IPO, but has an interesting, promising product in Phase II trials in the Notch pathway inhibitor Demcizumab.

Japanese Regenerative Medicine Regulatory Change Creates Buzz. The Japanese government has implemented regulatory changes that could speed the development of regenerative medicine therapies. The changes interest Cell Med biotechs including Mesoblast:

Mesoblast chief executive and founder Professor Silviu Itescu told Inside Business the bills enable Japan’s government to approve new products conditionally, providing their safety is confirmed in clinical trials, even if their efficacy has not yet been verified.

There are concerns, however, that a lack of data on efficacy may expose more patients to new products that have little chance to help them.

Disclosure: I don’t own stock in and am not affiliated with any of the companies mentioned above.