+Timos Papagatsias

Sunday 20 November 2011

AAV making a splash (?)

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Looking at Sanofi's early stage pipeline I noticed a couple of Gene Therapy products (coming through from Genzyme's pipeline) in Phase I development:
  • AAV2-sFLT01 for Age-related Macular Degeneration (AMD, more about this disease here
  • AAV2-hAADC2 (human Aromatic L-Amino Acid Decarboxylase-2) for Parkinson's disease
As can be seen by the names of the candidates, they both make use of adeno-associated virus serotype 2 (AAV2) gene delivery technology. Doing some research around how Genzyme got hold of this tech, I stumbled across Avigen Inc.; Genzyme appears to have licensed the AAV technology from Avigen in 2005 and has been developing products based on it since then. 

A quick search for "AAV" or "adeno-associated virus" on clinicaltrials.gov returns 9 ongoing Phase I and Phase II studies (with about another 50 or so studies that have previously been completed/terminated). It is interesting to note at this point, that it is mainly AAV2 or AAV1 serotypes that are being used in these studies, despite development of other AAV serotypes (from serotype 3 all the way up to serotype 11 as well as some of their hybrid versions such as AAV-2/5). This is not entirely surprising, given the experience that researchers have working with these vectors. A nice recent review on AAV-based gene therapy can be found here.

The main problems with this gene delivery approach revolve mainly around safety (avoiding unwanted effects due to virus integration in the host genome), identifying the vector serotype with the appropriate tropism for the target tissue/organ and quite importantly, being able to achieve production of large high grade GMP amounts of viral vector.

So, I would be interested to see how Sanofi's trials develop and how the FDA will look upon this approach. Looking at some other interesting news around AAV-based therapeutics, AMT's Glybera failed to get approval by the EMA earlier this year, although it had shown some promising results (more info about Glybera, the AAV1-based delivery of lipoprotein lipase can be found here). Glybera would have been the first gene therapy product to be marketed in Europe, however now the program is suspended and AMT is facing tough financial problems

In conclusion, it is pretty early days for an AAV-based therapeutic to hit the market although a few companies are working in the field. I would keep an eye out for news coming from Ceregene though as they have a strong advisory board (including R.J. Samulski) and that could translate into some interesting tech and positive clinical outcomes.