Thursday, July 3, 2008
Metabolic Disease Drug Development Anxieties Highlight Benefit of Diversified RNAi Therapeutics Pipeline
Now that I got this off my chest, what does the broad attack on metabolic disease drug development mean for RNAi Therapeutics?
Metabolic disease, because of the ability of current systemic delivery methods to effectively knock down genes in the liver which is critically involved in regulating blood sugar and lipid levels, is one of the main therapeutic focus areas of current RNAi Therapeutics development. It shares this position with cancer, followed by respiratory, ocular and CNS-related disease. It may therefore be tempting, if you have the ability to target a range of hot metabolic disease targets, to create a development pipeline based on metabolic disease and little else. ISIS Pharmaceuticals from the related field of antisense therapeutics is probably the best example here as it has very much limited their internal drug development activities on metabolic disease, while handing off some of the more challenging targets such as for cancer to one of their many satellite companies.
Of course, if you don’t have the capability to diversify, concentrating on building a franchise around a single, but potentially very lucrative market may be the most efficient way of maximizing shareholder value given the many synergies derived from largely having only to exchange the siRNA inside and comparatively few other changes. However, if you can afford it and you are interested in establishing RNAi Therapeutics as a broadly applicable drug development platform, you probably would want to spread your risk more widely even if all the programs added up individually would yield a higher valuation. The fact that the regulatory environment may change overnight while drug development is a 12-15 year effort being one reason.
Next to insuring from regulatory risk, diversification also means that failure of one drug candidate such as for a given organ does not necessarily have to impact the perceived probability of success for candidates aimed at other organs. In the same vein, it may also be wise not to be too dogmatic about delivery technologies, siRNA modification or DNA-directed RNAi methods and structures. For example, if your entire IP claim depends on just one siRNA modification pattern even without so much as functional validation in a non-human primate, you may have ended up totally reliant on clinically non-viable chemistries. Related technologies have shown that developing chemistries in generations rather than multiple chemistries in parallel may mean that if your chosen chemistry generation turns out to be either inefficient or unsafe, it may take another 7 years to get a shot with the next generation.
Meanwhile, all bets are off what steps the FDA will take next.
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