Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night!
1. The end of Chondrocelect
Beligian cell therapy company Tigenix announced plans for withdrawal of their autologous chondrocytes implantation product Chondrocelect from European market. This is business decision, due to competitors on a market and lack of reimbursement. Chondrocelect received EMA marketing authorization in 2009. From company’s press release:
Due to the regulatory environment around autologous chondrocyte-based cell therapy products in Europe leading to a difficult competitive landscape for ChondroCelect, together with the lack of reimbursement in key European countries, TiGenix has been prompted to initiate the withdrawal process of the Marketing Authorization for ChondroCelect® for commercial reasons. Consequently, TiGenix has come to an agreement with Sobi for the early termination of their existing commercial relationship and will also terminate its manufacturing agreement with PharmaCell.
I think, this is big blow for the field. One more cell therapy product was not doing well on a market after approval. Now it’s a part of history. For quite similar reasons, Genzyme/Sanofi withdrew their ACI product MACI in different countries and closed manufacturing sites.
The claim that regulation is too harsh wrongly implies that the FDA is holding back therapies that work. Critics point to decades of preclinical and clinical work with stem cells and the pipelines of stem-cell treatments. With circular logic, they argue that, because the treatments have not been approved, there is something wrong with the approval system.
The assumption in these accusations — that these treatments work — is at the heart of the problem. The FDA is right to insist that only proper clinical trials can make that case. And the agency’s critics are right to point out that this process is lengthy and expensive — perhaps too much so.
I think, the editorial got some things right (for example, yes – absence of stem cell products on a market does not necessarily mean that FDA is too harsh, it could means that all product-cadidates are suck), but some statements could be wrong or too simplified. Nature is bringing Turner/ Knoepfler study to say “that the FDA is not unduly harsh”. But it could be not the case. It could be because FDA does not have enough funding and manpower to fight with a scale of these clinics and police all of them. We do not know for sure. Another thing is that editorial portrays new Japanese Regenerative Medicine law as “patients rip-off”, but not like conscious decision of government and people of Japan.
3. Deaths in CAR T-cell therapy trial
CAR-T Deaths Cannot Be Good (In The Pipeline) – read comments!
CAR T-cell therapy developer Juno Therapeutics announced clinical hold of their Phase 2 ROCKET trial, triggered by death of patients. The trial was suspended by FDA. Because CAR T-cells is currently the hottest area of cell therapy, Juno’s news made a big buzz in the social media. Links to some interesting coverage below:
Juno Therapeutics Stops Trial Of Cancer-Killing Cells After 3 Patient Deaths (Forbes)
Juno scrambles to avoid being crushed by a hold, but experts question its best case scenario (EndPoints)
Are patient deaths in the Juno cancer trial just a ‘bump in the road’? (STAT/ Pharmalot)
Is Juno’s hold a CAR crash or just a speed bump? (EP Vantage)
Unexpected Deaths Put Promising Immunotherapy on Hold (MIT Tech Review)
4. CAAR-T cells for targeting of autoimmune diseases
Researchers from University of Pennsylvania for the first time described new type of CAR T-cells, engineered to target auto-antigen – chimeric auto-antibody receptor T-cells (CAAR). From NIHilist’s Immunology blog:
This new technology is based on a simple idea: antigen decoy. For example, during pemphigus vulgaris autoimmune B cells secrete autoantibodies to the keratinocyte adhesion protein desmoglein (Dsg3) that causes severe skin inflammation. Short-term management of diseases is achieved by total B cell depletion, but disease returns. The authors reasoned that if engineered T cells would express Dsg3 as a CARs, such antigen decoy CAAR T cells would selectively engage disease-causing anti-Dsg3-specific auto-antibody producing B cells. Such interaction should eliminate only Dsg3 specific B cells, sparing normal, infectious-specific B cells.
5. Stem cell gene therapy in Gartner Hype-Hope curve
LifeSci VC blog posted very interesting analysis of hype-hope cycle in so-called stem cell gene therapy (means CD34+ cell-based gene therapy of inherited immunodeficiencies). This analysis is based on recent EMA approval for gene therapy product Strimvelis (GSK). The authors think that European approval of Strimvelis is a first sign of “plateau of productivity” in Gartner’s curve:
With a switch from T cells to stem cells and a roller-coaster hype ride, the gene therapy field has delivered on its promise from over 25 years ago with a medicine that now offers a real hope for children with ADA-SCID. At the heart of the journey to Strimvelis are patients and their families, starting with Ashanti DeSilva who was the first ADA-SCID patient to receive gene therapy with her own modified T cells. We owe a huge debt to the brave families who enrolled their children on clinical trials, together with the clinical giants who led this work and provided vital learnings for the adjacent fields for the future. The next chapters for CAR-T and gene editing will be compelling, especially if they are able to both seed new technology developments and bring curative medicines to patients.
6. Shoukhrat Mitalipov’s profile
STAT posted a profile article about mitochondrial genome transfer pioneer Shoukhrat Mitalipov. Very good article, highly recommended!
His whole career, Mitalipov said, has consisted of tinkering with the nuclear transfer techniques that Campbell, who died a few years ago, developed in the mid-90s.
“My clinical goal was to use some of the basic knowledge to improve human reproduction,” Mitalipov said. “The IVF platform can be used now to remanufacture gametes, to treat infertility, but also as a platform for gene therapy, which is probably where the future will go.”
7. Trends in NIH-funded stem cell workforce
The authors of recent analysis, published in Cell Stem Cell, looked at aging of NIH-funded workforce with focus on stem cell research. Take home message – more government money go to older stem cell researchers. More detailed conclusions:
The stem cell research workforce has expanded over the past decade and a half. Even though it is a “relatively” new field given NIH’s history, it faces some of the similar issues experienced by the entire research community. It is also aging. The number of NIH R01-equivalent applications from older stem cell investigators has been growing at a faster rate than younger investigators and competition for funding is intense. However, retirement-age replacement ratios are increasing. As with the entire biomedical research workforce, stem cell researchers who are dependent on NIH for research funding will also have to examine the culture and environment in their institutions and work with federal agencies and other funders to find creative and innovative solutions to help reduce the stress on an aging workforce system within a limited-resources environment.
Also read coverage by Science 2.0
8. Fresh free reviews:
Human-animal chimeras: ethical issues about farming chimeric animals bearing human organs (Stem Cell Res Ther)
Cellular Reprogramming Using Defined Factors and MicroRNAs (Stem Cells Int)
Efficacy of MSC therapy for acute lung injury in preclinical models (PLoS ONE)