The graveyard of RNAi efforts is vast and includes failed and canceled attempts by Novartis ($NVS), Merck ($MRK) and Roche ($RHHBY). But Sanofi ($SNY) committed to the drug delivery paradigm in early 2014 by purchasing a 12% stake in leading RNAi specialist Alnylam ($ALNY) for $700 million.
The deal demonstrates Big Pharma's partnership- (and checkbook-) oriented strategy toward R&D. The pharma bigwigs' lack of homegrown innovation means more funding opportunities are available to drug delivery specialists like Alnylam.
Sanofi's bold move builds on an alliance that's been in place since 2012. The company's rare disease subsidiary Genzyme is working with Alnylam to develop its candidate (dubbed patisiran) for the genetic disorder TTR-familial amyloid polyneuropathy in exchange for marketing rights outside of North America and Western Europe. Previously, Sanofi had commercialization rights in only Japan and the Asia-Pacific region.
After promising Phase II results, the candidate is now recruiting patients for its Phase III trial of 200 patients, according to ClinicalTrials.gov.
Sanofi is also co-developing a candidate (revusiran) for the genetic disease familial amyloid cardiomyopathy in exchange for commercialization rights outside of North America and Western Europe. The Phase III trial of revusiran was initiated in December, Alnylam says.
Finally, under the terms of the upgraded alliance, Sanofi's Genzyme acquired full global or co-commercialization rights to two additional Alnylam candidates following the completion of early clinical trials. It also has the option of developing and commercializing all of Alnylam's rare genetic disease products outside of North American and Western Europe until 2020, according to the release announcing the $700 million investment.
The problem is, so far there are no products to commercialize. But Alnylam believes it can be first to bring an RNAi drug to market thanks to its two aforementioned Phase III candidates and novel drug delivery platform, or enhanced stabilization chemistry-GalNAc-conjugate technology. Many companies use lipid nanoparticles to deliver RNAi to the correct site in the cell. Alnylam instead attaches the RNAi to a sugar molecule, enabling subcutaneous (as opposed to intravenous) delivery.
|Alnylam COO Barry Greene|
Perhaps unsurprisingly given RNAi's unproven status, 2014 was a volatile year for the company. Amid since-quashed fears of a biotech stock bubble and Novartis' ($NVS) abrupt exit from RNAi research, Alnylam COO Barry Greene defended the company's turf, telling FierceDrugDelivery in April 2014 that Big Pharma has "never been able to innovate" and "has been a miserable barometer of high impact technologies," in what was a bid to stem a sliding stock price by going on the offensive.
The company's been mainly focused on rare diseases, with the exception of hepatitis B. But Chief Business Officer Laurence Reid hinted that it is on the lookout for more alliances in bigger therapeutic areas. "I think we'll take more of a partnership-driven approach to moving into those bigger disease areas," he told investors in October.
RNAi accomplishes gene silencing by cleaving messenger RNA within cells' cytoplasm, preventing gene transcription from taking place. The naturally occurring paradigm's discovery in 1998 earned scientists Andrew Fire and Craig Mello a Nobel Prize in 2006.
The biological pathway presents a true drug delivery challenge because the genetic material used is fragile and easily breaks down in the body but must remain intact to have any therapeutic use, since it silences undesirable genes inside cells.
-- Varun Saxena (email | Twitter)
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