Authored by James Sheppard
There are many areas of pharmaceutical innovation currently receiving considerable attention, both for their scientific potential in a personalised medicine era but equally because of the potential they offer to investors. Gene Therapy is one such area and its resurgence has been garnering interest across the globe, leading to regulatory approvals, licensing and alliance deals, investments and scientific breakthroughs. Earlier this year we featured an article on this resurgence in Gene Therapy and here we take a more in-depth look at some of the recent occurrences.
Until recently, academia has been the main proponent of Gene Therapy, with very few programmes making the step into translational research and development or first in man studies. However, more recently a spate of positive Gene Therapy news has emanated from academic circles. Most notably, researchers at The Cardiovascular Research Center, Ichan School of Medicine at Mount Sinai have shown that an inhalable gene therapy can completely reverse pulmonary arterial hypertension (PAH) in rat models. Significant inroads have also been made, in rare diseases such as Wiskott-Aldrich Syndrome, Canavan Disease, Spinal Muscular Atrophy and Friedreich’s Ataxia to name just a few.
The transition from academic research to human testing (clinical trials) is one of the largest stumbling blocks for any drug on the path to commercialisation. This is no different in gene therapy. The very considerable financial and human resources which trials demand often require industry participation to help fund and operate those trials, so increased collaboration between industry and academic centres is a key feature of the Gene Therapy market.
Pharma powerhouses have been drawn to these collaborations and in August 2012 global pharmaceutical giant Novartis announced a collaboration with University of Pennsylvania Advanced Cellular Therapy Center for the study, development and commercialisation of novel cellular therapeutics for oncology. Their UK rivals, GSK, have also been working in the gene therapy area as part of their rare disease franchise. GSK have a partnership with the charity-funded San Rafaelle Telethon Institute for Gene Therapy (TIGET) in Milan, Italy. GSK gained an exclusive licence to develop and commercialize the adenosine deaminase deficiency (ADA) treatment, and will co-develop with TIGET gene therapies for six more genetic diseases. In areas of rare diseases, funding from foundations and charities has been a growing feature of the financing picture and illustrates acutely the multi-stakeholder approach in de-risking and advancing new innovations in areas like Gene Therapy.
Earlier this year, US biopharma BioMarin made its first foray into gene therapy when it licensed a Factor VIII gene therapy program for hemophilia A from University College London and St. Jude Children’s Research Hospital. The company is conducting preclinical studies and expects to advance a development candidate to proof of concept human clinical studies by the end of 2014. The market for hemophilia A products is today worth around $6 billion a year and there are some 90,000 patients in markets where Bio-Marin has commercial operations.
The first regulatory approval of a gene therapy in the western world, Glybera, was really the booster the industry required. Glybera was in regulatory terms the ‘canary in the coal mine’ for Gene Therapy. It was developed by the Dutch company uniQure (formerly AMT). Today, uniQure is busily working out the pricing strategy for Glybera. Given it is the first commercial Gene Therapy product, it presents certainly complexities and the company is presently looking to acquire specific expertise to assist this process. The rumours which have surrounded the pricing and reimbursement are that uniQure will price the product on an annualised basis, linking the price to ongoing in-patient clinical or therapeutic benefit, rather than a ‘one off’ price. People from across the rare disease sector continue to observe this outcome with great interest.
In order to aid commercialisation of Glybera, uniQure has raised $10m in venture debt from Hercules Technology Growth Capital to finance the building of a 55,000 sq ft US manufacturing site. The site based in Lexington, Massachusetts will be for commercial grade Adeno Associated Virus (AAV) gene therapy products. UniQure also announced that they had signed a deal with European pharmaceutical company Chiesi for the commercialisation of Glybera. The deal will also see Chiesi and uniQure collaborate on the development of a gene therapy for haemophilia B.
UniQure have also recently announced the initiation of a human trial in Parkinson’s disease. The gene therapy was developed by researchers at University of California (UCSF) and uses the GDNF gene which uniQure licensed from Amgen. The trial is part of a wide ranging collaboration between uniQure and UCSF looking at gene therapy across a number of disease indications including Huntington’s disease and Multiple System Atrophy (MSA).
Bluebird bio, another innovating talisman in Gene Therapy, announced the closure of its initial public offering (IPO) in June. The company raised over $116m from the IPO which it added to previous venture financing in excess of $130m since 2010. Bluebird bio also struck a pioneering deal with biopharma heavyweight Celgene. Bluebird bio and Celgene have partnered with Baylor College of Medicine, USA in a potential deal worth over $250m. The deal is to help develop and commercialise novel disease-altering gene therapies in oncology.
Boehringer Ingelheim, the German pharma giant, also announced its foray into gene therapy by injecting an undisclosed amount into the French company Evevensys. Evevensys are developing gene therapies for treatment of the eye. Evevensys is now looking to add more investors to its portfolio after securing Boehringer in its second round of funding. In addition to money, Boehringer is contributing guidance; the drugmaker’s head of non-clinical R&D Dr. Michel Pairet has joined the Evevensys board of directors. Evevensys was not the only French gene therapy company to recently receive funding. GenSight Biologics announced they had raised 32m Euros in Series A funding provided by Novartis Venture Funds, Abingworth and Index Ventures. GenSight are developing gene therapies for Leber’s Hereditary Optic Neuropathy (LHON) and an optogenetic therapy for retinitis pigmentosa. GenSight’s lead product for LHON is expected to enter the clinic in 2013.
Gene therapy has always had a home in rare diseases. Therefore it is no surprise that rare disease behemoth Genzyme (Sanofi) has seized the opportunity. Genzyme recently announced the completion of a deal with US based biotech Asklepios BioPharmaceutical (AskBio). The deal grants Genzyme the rights to AskBio’s Duplex gene therapy vector where Genzyme will use it for internal product development. Genzyme currently has 2 gene therapy products in phase I clinical studies for Parkinson’s and Age-related macular degeneration.
The gene therapy field has come a considerable way, overcoming many hurdles and critics who were ready to dismiss its potential. However, the field is now moving forward with considerable pace and promise. Projects that were once funded by charities and academia are now being taken on by global pharma companies with the resources, financial and human, to push them forward. It is still early days for gene therapy with, at present only one approved and non-commercialised product. This rapidly evolving field has to address a number of key issues regarding pricing and reimbursement in an increasing stringent pricing environment. For now though, we celebrate its progress and look forward to increased innovation in Gene Therapy among collaborative stakeholders looking to bring to market Gene Therapy in a personalised medicine environment.