hare (them) vs tortoise (us), page-2

Not sure if this one has been posted elsewhere or not? From the Oxbridge biotech seminars:

http://www.oxbridgebiotech.com/review/obr-news/la-london-discusses-future-gene-therapy-ageing-novelty-investment-hotspot/

OBR-LA and OBR-London discuss the future of gene therapy: ageing novelty or investment hotspot?

Thursday, 3rd April 2014

By Francesca Chiara, OBR-London Chapter Correspondent; Ray Xiong, OBR-LA Chapter Correspondent

On 13th and 19th March, OBR-LA and OBR-London, respectively, each hosted a panel of 4 experts from the academic, biotech and investment communities to discuss the risks and future prospects of gene therapy. The London event was kindly sponsored by the King’s College London Dental Institute.

In the early nineties, scientists had hoped that gene therapy would cure all human disease. It is clear today that this will not be the case.

To date, there is no approved gene therapy drug in the United States. In Europe, Glybera is the only commercially available and officially approved one. Dr. McBlane from the UK’s MHRA, who was heavily involved in the approval of Glybera in 2012, explained that it is a gene therapy product designed to restore a lipoprotein lipase deficiency, which is administered via 50 intramuscular injections into the leg at one time. In his opinion, the long-term benefits of such a drastic treatment are still unclear.

Audience at the event in London.
Audience at the event in London.
So why aren’t there more gene therapy products in the clinic? Dr. Griesenbach, Reader at Imperial College London, whose research focuses on gene therapy, mainly but not exclusively for cystic fibrosis, replied that at the beginning there was a lot of excitement about it, but soon academia and industry started losing interest due to the technical difficulties. But there is still potential. Primary immunodeficiencies played a key role in the development of gene therapy combined with cell therapy treatments for systemic diseases. Since 2005, improvements in gene transfer techniques led to exciting new clinical data. Previously, the success of ex-vivo viral vector-mediated gene transfer into autologous haematopoietic stem cells has been shadowed by insertional mutagenic events causing tumours in treated patients. The recent use of self-inactivating vectors has now improved the safety and led to new studies that are showing early signs of efficacy [1].

Dr. Mackenzie, a serial entrepreneur in multiple gene therapy firms, argued that gene therapy has proven inefficient so far because the majority of the early scientific efforts were focused on systemic cures – such as for cancer or HIV – that required molecules to be delivered to most parts of the body. These key molecules, called vectors, contain the therapeutic genes and are notoriously difficult to deliver into cells. He believes that gene therapy, without the aid of cell therapy, would be best applied to treat diseases that are restricted to distinct regions in the body where you can directly apply the vectors, such as the eye or the brain. The idea of transferring genes into a human body by simply injecting them into the bloodstream is still science fiction.

Dr. Hollowood, Partner at Syncona Partners and Chairman of NightstaRx Ltd., a spin-out retinal gene therapy company from the University of Oxford, stressed that gene therapy is not efficient because the vectors were and remain difficult to develop and optimize. There is also a lot to be done to improve the quality and efficiency of manufacturing the treatments at scale.

At OBR-LA, the discussion focused on starting a venture in gene therapy. Prof. Zaia, Chair of Virology at City of Hope and head of the Cytomegalovirus Laboratory, introduced three main risks for this type of venture: scientific, clinical and financial.

From a scientific and clinical point of view, Prof. DiGiusto, Research Professor of Virology and Director of the Laboratory for Cellular Medicine at City of Hope, warned that vectors can trigger severe immune responses and cause mutations in the patients’ DNA that could later lead to tumour insurgence. Dr. Griesenbach explained that two types of vectors may be used: viral and non-viral. Viral vectors are extremely efficient but highly immunogenic, while non-viral vectors are less efficient but safer.

On the financial aspects, Dr. Griesenbach at OBR-London highlighted the key problem for academics in the UK is that it is almost impossible to source enough funding from government bodies or charities in the UK to fund large clinical trials: she is aware she will likely have to hand over her beloved research to industry for the final stages of testing. Mr. Louis Breton, CEO and Co-founder of Calimmune Inc., shared his thoughts at the OBR-LA event on the business side of gene therapy from a small biotech perspective. As a biotechnology company, there are three key steps: choosing the therapeutic market, achieving uptake by doctors, and eventually building a business. Pitfalls in any of the three steps will compromise the health of the business.

The business model for gene therapy remains tricky: the product has a phenomenal R&D cost, but it is only bought once by each customer. Exit for gene therapy companies via acquisition by big pharma is very uncertain at this moment and with so many unknowns in the long-term health effects of the treatments, patient demand is also unclear. In the UK, Dr. McBlane is certain that patients will not be able to rely on the NHS to pay for such expensive treatments, but if the treatment proves to be truly effective, who is to say that a patient wouldn’t sell his/her house to pay for it. (The reimbursement issue is covered in depth by this Xconomy article.)

To answer the question raised by OBR-London, is gene therapy an investment hotspot or ageing novelty? Dr. Hollowood elegantly replied,

“Gene therapy is an ageing novelty, and therefore an investment hotspot.”

For the exact reason that the field now recognizes and understands much better the limitations of the technology, he believes that R&D will be more strategically focused than ever on finding cures for diseases tractable for gene therapy.

The optimism was also strong in LA: “The only risk is not to take the risks” remarked Mr. Breton. The panelists’ consensus is that, where the risk outweighs the current lack of options for certain life threatening orphan diseases, gene therapy is worth it. The newly developed gene editing techniques such as ZFN, TALEN, and CRISPR also bring new hopes to the field (2). “Good science still leads to good business,” concluded Dr. Burke.