RegenMed, stem cell and cell therapy industry in 2014

by Alexey Bersenev on December 30, 2014 · 1 comment

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This is my annual overview the most interesting and important events in stem cell/ RegenMed/ cell therapy industry. It was very very eventful year! So, it was hard to pick “top 10” and I combined some related events in one topic or trend. Please share your impressions and opinions about 2014 industry events!

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1. Safety of commercial ESC-derived product candidates
Since 2009, when FDA approved first embryonic stem cell (ESC)-based clinical trial in US, we have been eagerly waiting any news about safety of this controversial type of cells. This year, for the first time, 2 companies released preliminary mid-term safety results of transplantation ESC-derived commercial product candidates. In May, Asterias Biotherapeutics (subsidiary of BioTime) – a company, which acquired Geron’s stem cell assets, released safety results of the first 5 cases of ESC-derived neural cells in patients with spinal cord injury (treated by Geron). In September, Ocata Therapeutics (formerly Advanced Cell Technology) published the first report of mid-term safety results from their two ESC-based trials. They demonstrated that allogeneic ESC-derived product is safe up to 2-3 years after implantation into the eye of individuals with macular degeneration. Remarkably, no patients, treated with ESC products in either the Ocata or Geron (Asterias) trials, reported any major cells-related adverse events, such as excessive tissue growth or immune rejection.

2. The end of Regenerative Sciences versus FDA case
On February 4th of 2014, US Federal Court ruled in favor of FDA in long-term case with Regenerative Sciences. It was historic court case, started in 2008. The impact of the case is establishing current regulatory rules in USA, where autologous cells cultured ex vivo, should be regulated as drugs, but not as practice of medicine. You can read a Court report here and some coverage here, here, here and here. Regenerative Sciences will not pursue appeal to the Supreme Court. This case triggered probably the biggest discussion in the last 5 years in cell therapy field – regulation of autologous cell products.

3. New wave of commercial embryonic stem cell-based trials
This year we have witnessed a new wave of interest from industry to ESC-based clinical trials and new products development. Two important catalysts for this change (Asterias and Ocata data release) I’ve mentioned above. A number of new ESC-based trials are just starting. Asterias got approval of FDA in August to re-start spinal cord injury dose escalation trial. A new player on “eye diseases market” – CellCure Neurosciences (BioTime subsidiary) got FDA approval for start of trial, which will assess product OpRegen in age-related macular degeneration. The company is starting to enroll patients in Israel. US-based company ViaCyte, got IND approval for using of ESC-derived islet-like pancreatic cells in diabetes in August, and has treated the first patients in University California San Diego. Notably, ViaCyte became the first private company, which attracts attention of Pharma industry. In August, ViaCyte and Janssen Pharmaceutical Companies of Johnson & Johnson signed an agreement for evaluation of company’s candidate ESC-based product VC-01.
Read more about latest development in pluripotent stem cell-based therapies in my recent essay.

4. Efficacy failures of cell therapy trials
Despite many reports about success of early stages (1/2) cell therapy trials, some of them started to fail in later (2/3) stages. In April, US-based company Athersys announced results of stem cell product MultiStem infusion in ulcerative colitis. Unfortunately, this randomized, placebo-controlled trial failed to meet efficacy end points in interim readout. The trial was conducted by Pfizer (Athersys partner) in US, Canada and Europe. Yet another Phase 2 trial, conducted by AlloCure, which assessed mesenchymal stromal cells in acute kidney injury, was terminated in August due to futility. Finally, results of failed Cardio 133 trial, sponsored by German company Miltenyi Biotec, were published this year.

5. Divesting of stem cell/ RegenMed assets
Divesting is quite unusual word for RegenMed industry, but we heard it frequently this year. First, Shire divested regenerative medicine product Dermagraft to Organogenesis in January. Did Shire make a mistake when acquired this asset? Read about possible reasons here. Second, Sanofi divested 3 products – Carticel, Epicel and MACI to Aastrom (now Vericel Corp.) in April. Sanofi inherited cell therapy assets with acquisition of Genzyme in 2011. Interestingly enough, two “tools/ reagents” companies “got rid of stem cell assets” this year as well. French company Cellectis sold stem cell program to Japanese firm Takara. The decision was strategic ans based on “operating net loss“. Next, Stemgent divested stem cell business unit to Japanese company ReproCELL.

6. Acellular RegenMed products launched on a market
There were no notable approvals of new cell therapy products on a market this year. But a lot of acellular scaffolds and matrices were approved and launched. I was able to count at least 5 products: (1) decellularized porcine liver product MiroMesh by MiroMatrix approved by FDA as 510k device for hernia repair, (2) hydrogel Premvia by BioTime approved by FDA as 510k for wound repair, (3) acellular bovine pericardium-derived cardiac patch CardioCel by Admedus was cleared on US, Canada and Singapore markets, (4) porcine small intestine-derived extracellular matrix CorMatrix ECM by CorMatrix was approved by FDA as vascular patch and (5) decellularized human dermis product DermaPure by Tissue Regenix was launched on US market for wound repair.

7. CART shakes Wall Street
This year few more companies got into commercialization of gene-modified T-cells in oncology, or so-called CART. Impressive clinical data (check reports from ASH 2014) backed up such fast commercialization and big interest from investors. Three companies, which explore CART-cell therapies in clinc, went public this year with successful IPO. Juno Therapeutics ($JUNO) went public just about a week ago and was able to pull $265M IPO. It was the biggest Biotech IPO of 2014. Bellicum Pharmaceuticals ($BLCM) pulls $140M from its IPO in December. But probably “iconic” for CART investors was performance of Kite Pharma ($KITE) since its $128M IPO in June. The company was growing steadily whole year, finishing it with +93%. So, this year, Wall Street fell in love with a CART cell therapy.

8. Bankruptcies
One of the biggest unfortunate events of 2014 was a bankruptcy of cellular immunotherapeutic pioneer – Dendreon. The company made a history with the first cell therapy drug approval in US in 2010 and blazed a trail for other commercial players in cancer cellular immunotherapy. Unlike some professionals, I think, it is a big failure and there were many many reasons for it. You can read some analysis and discussions here, here, here, here and here. Because company was not able to find a buyer until now, it is heading to “auction without initial bidder“. Dendreon will definitely be in “cell therapy textbooks”, because we can learn a lot from its failure.
Yet another legendary pioneer, but from tissue engineering field – Tengion, failed for bankruptcy protection few days ago. This public company is developing tissue engineered kidney prototype. Tengion was founded and backed up by “tissue engineering star” Anthony Atala from Wake Forest Institute for Regenerative Medicine. The company is struggling for a long time to raise money for clinical trials and R&D.

9. CRISPR genome editing IP battle
New tool for genome editing CRISPR/Cas9-based techniques is probably one of the biggest and significant discoveries of this century. It is a good candidate for Nobel Prize in the future. However, it is very unclear who owned the discovery and who will have rights and patents. There is a number of companies, commercializing CRISPR-based technologies in medicine (CRISPR Therapeutics, Editas Medicine, Caribou Biosciences, Intellia Therapeutics) – all of them can have intellectual property (IP) issues. The history behind discovery is quite complicated and summarized here. This year, one of “CRISPR pioneers” Feng Zhang from MIT got the first US patent. This event facilitated “IP battle” and triggered a lot of discussions. You can read nice coverage of the problem here, here, here and here.

10. Cell therapy whistleblowers
Something very interesting and unique happened this year in stem cell therapy field – we witnessed whistleblowing for the first time! First, Rob Williams – a former employee of StemCells Inc sued a company for false claims about quality of current cell manufacturing practices. Second, Robert Sexauer – a former employee of Intellicell is suing company with group of investors for “for misuse of funds and alleged fraud“. Both whistleblowers made public comments about companies wrongdoing. We don’t know yet the outcomes of these cases, but will follow it next year.

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Disclaimer: I have no financial interest in companies, mentioned in this post. Information, presented in this post should not be considered as financial advice. I’m involved in CART cell therapy trials, conducted in University of Pennsylvania.

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RegenMed Digest on StemCellAssays is sponsored by Regenerative Medicine Jobs. Please visit Regenerative Medicine Jobs for recent position openings.

{ 1 comment… read it below or add one }

Logribel February 15, 2015 at 12:06 pm

Hi Alexey,

First, thanks a lot for your informative and thoroughly researched blog!

Since there doesn’t seem to be (yet) a blog entry about your expectations for the stem cell industry in 2015, I am very curious to know your opinion on TiGenix’s upcoming events. The company — after some rough years of financing pursuit — is finally going to deliver preliminary topline results for its phase 3 allogeneic adipose-derived MSC trial in treating Crohn’s fistulas later this year (anticipated for July 2015).

Since phase 2 was one of the very rare allogeneic trials to actually demonstrate statistical efficacy in a placebo-controlled, single-blind trial — although on a small population (N=24) — odds don’t look too bad for a phase 3 success in this indication.

Here’s the phase 3 ongoing trial: https://clinicaltrials.gov/show/NCT01541579

That could become, I believe, the very first success ever for a phase 3 allogeneic MSC trial this big (N=278)… Obviously, the quality of TiGenix’s previous trials for this indication is a fact recognized by the FDA as ongoing talks between the regulatory body and TiGenix lead to the filing of a special protocol assessment that would allow for a single phase 3 pivotal trial in the US before commercialization:

http://bit.ly/19kBMcE

Don’t you think that would be a major event in the stem cell field? Wouldn’t that be a nice subject for your ongoing “products in the pipeline” series, since TiGenix’s cell product is also being tested for early RA and severe sepsis?

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