This article has been updated with additional details about the strategic alliance.
Alnylam Pharmaceuticals this week announced that it has signed a deal to develop and commercialize RNAi-based treatments for TTR-mediated amyloidosis with Genzyme, giving the Sanofi subsidiary product rights in Asia.
For Alnylam, the deal marks the signing of its latest strategic alliance with a major biopharmaceutical firm — a key milestone for the company, which has been more cautious about providing specific partnering guidance after missing projections in recent years.
For Genzyme, the arrangement represents its latest effort to play in the oligonucleotide therapeutics space through tie-ups with companies in the field following its mostly successful partnership with Isis Pharmaceuticals on the cholesterol-lowering antisense agent mipomersen.
Alnylam's ATTR program has thus far yielded two drug candidates. Both comprise siRNAs targeting the wild-type form of the protein transthyretin, as well as the disease-causing mutant form, but each uses different delivery vehicles.
The first, called ALN-TTR01, used a lipid nanoparticle licensed from Tekmira Pharmaceuticals. The second, ALN-TTR02, uses a next-generation lipid that Alnylam claims is proprietary, although the companies are currently embroiled in a legal battle that has both claiming ownership of both lipids.
This summer, Alnylam reported solid phase I data on ALN-TTR02, showing that the drug triggered up to 94 percent reductions in levels of its target protein after a single dose (GSN 7/19/2012). A couple of months later, Alnylam disclosed that it plans to file an investigational new drug application on a subcutaneous version of ALN-TTR02, which uses its GalNAc conjugate delivery technology, by the end of the year (GSN 8/9/2012).
These data “demonstrate impressive clinical activity and support advancement of this promising therapeutic into pivotal studies and toward the market,” Genzyme President and CEO David Meeker said in a statement, noting that a phase III trial of the systemically administered version of ALN-TTR02 is slated to begin in 2013.
Under the terms of their deal, Genzyme will pay Alnylam $22.5 million in cash up front in exchange for the rights to the TTR program in Japan, where the disease is endemic, and other Asia-Pacific countries including Korea, Australia, and China, the companies said. Alnylam also stands to receive milestones of up to $50 million and tiered royalties in the mid-teens to mid-twenties.
Alnylam retains the full rights to the program in the US, Europe, and the rest of the world, and each company is entirely responsible for the development and commercialization of ATTR therapeutics in their respective markets.
An Alnylam spokesperson confirmed, however, that the companies will work together to advance their drug candidates, "sharing clinical data and strategies from our respective territories in a mutual effort to get [these] drugs to patients in need."
In a filing with the US Securities and Exchange Commission, Alnylam noted that the companies also "intend to enter into a supply agreement" under which Genzyme will be supplied with drug material for clinical studies and, potentially, commercial sales. Genzyme also has the option to manufacture drug materials itself or hire a third-party manufacturer.
Additonally, Genzyme has the right of first negotiation to ATTR products within Alnylam's territories if Alnylam decides it wants to license them out to third parties.
In landing Genzyme as a partner, Alnylam has further fulfilled CEO John Maraganore's prediction earlier this year when he said that the company expects to “do partnerships” in 2012, without getting into specifics because “it would be premature to say when [a deal will be struck] and what phase we're at” in ongoing negotiations (GSN 2/16/2012).
Previously this year, Alnylam also pulled in a $29.2 million payment from Monsanto for the exclusive, global rights to its RNAi technology and intellectual property for agriculture applications (GSN 9/6/2012). And in July, Alnylam licensed the Chinese rights to its phase I liver cancer drug ALN-VSP to Ascletis Pharmaceuticals (GSN 7/12/2012).
Overall, however, Alnylam has been more measured about giving partnership guidance, having failed to live up to promises in past years. For example, the company was unable to find two or more partners in 2009, a goal put forth at the beginning of that year (GSN 3/4/2010).
Still, in May, Alnylam President and COO Barry Greene said that the firm would secure partnerships for ALN-VSP and for its phase I hypercholesterolemia drug ALN-PCS by year end. Counting the Ascletis deal, Alnylam has about two months to find a taker for the cholesterol program, which it said won't be advanced into further clinical testing without a partner.
Meantime, through the ATTR arrangement, Genzyme has found its latest oligonucleotide therapeutics partner in Alnylam, which reflects the company's ongoing effort to build out its pipeline internally, as well as through external collaborations, Meeker added in his statement.
When it comes to RNA medicines, that approach has thus far proven a good one. In early 2008, Genzyme formed a strategic alliance with Isis to develop and commercialize the phase III drug mipomersen, which is designed to lower cholesterol by silencing apolipoprotein B-100. Genzyme also picked up “preferred access” to future Isis drugs for central nervous system diseases and certain undisclosed rare diseases.
In exchange, Isis received $325 million in upfront cash and equity investments, plus milestones and profit-sharing rights.
This month the drug, now branded as Kynamro, received the recommendation of the US Food and Drug Administration's Endocrinologic and Metabolic Drugs Advisory Committee after the panel voted 9 to 6 that Genzyme had provided sufficient safety and efficacy data supporting the compound's use in patients with the rare condition homozygous familial hypercholesterolemia.
While the panel was divided on the drug in light of data suggesting liver toxicity and, possibly, a cancer risk associated with the drug, the FDA typically follows the recommendations of its advisory committees. The agency is expected to make its final decision by the end of January 2013. An application for the drug is also under consideration by European Union regulators.