Alnylam Pharmaceuticals announced this week that it has halted development of its most advanced RNAi therapeutic candidate, the age-related macular degeneration treatment ALN-VEG01, and shifted its focus to its respiratory syncytial virus drug program.
The move was no surprise in light of statements President and CEO John Maraganore made last month regarding the increasingly competitive AMD field (see RNAi News, 8/12/2005). During a mid-August conference call to discuss Alnylam's second-quarter financial results, he said that the company was considering dropping its AMD program in light of strong clinical data on more advanced AMD treatments being developed by other drugmakers.
Alnylam's decision to bow out of the AMD arena also prevents possible competition with Novartis, which is developing the AMD drug Lucentis with Genentech and earlier this month signed an RNAi alliance with Alnylam that could be worth more than $700 million.
Alnylam had been on track to begin clinical testing of ALN-VEG01 before the end of the year, which would have made it the third RNAi drug company to have an AMD drug in phase I testing behind Acuity Pharmaceuticals and Sirna Therapeutics. All three drugs target the VEGF pathway, whose role has been well established in AMD.
"Given the reported efficacy in recent phase III studies from competing drugs targeting vascular endothelial growth factor for the treatment of age-related macular degeneration, the company has made the strategic business decision to suspend further development of ALN-VEG-01 … in order to allocate resources to other product opportunities."
However, Alnylam said this week that "given the reported efficacy in recent phase III studies from competing drugs targeting vascular endothelial growth factor for the treatment of age-related macular degeneration, the company has made the strategic business decision to suspend further development of ALN-VEG01 … in order to allocate resources to other product opportunities."
Topping the list of "competing drugs" is Genentech's Lucentis, a humanized antibody fragment designed to bind to and inhibit VEGF-A. At the American Society of Retina Specialists meeting this summer, Genentech presented one-year data from a phase III study of 716 patients showing that monthly intraocular injections of the drug helped prevent vision loss. Importantly, Lucentis-treated patients also experienced an improvement in visual acuity compared with controls, whose vision continued to deteriorate.
Genentech has also submitted the drug to US regulators for a fast-track designation and said it could begin the process of seeking regulatory approval for the drug as early as the end of this year if the designation is granted.
Under a 2003 agreement, Genentech is developing Lucentis in collaboration with Novartis. The deal gives Novartis the exclusive commercialization rights to the drug in all markets outside of North America.
Earlier this month, Novartis and Alnylam announced that they had struck a three-year partnership under which Alnylam would optimize lead RNAi therapeutic candidates for Novartis (see RNAi News, 9/9/2005). Novartis will then move the drugs into the clinic and potentially onto the market. Under the terms of the arrangement, Novartis will make payments of roughly $56.8 million to Alnylam, consisting of cash and equity purchases. Upon consummation of the deal, Novartis will hold a 19.9 percent stake in Alnylam.
Officials from Alnylam were not available to comment on whether the company's partnership with Novartis played a role in the decision to exit the AMD field.
Alnylam was developing AMD-VEG01 with Merck as part of a broader ocular disease collaboration between the companies (see RNAi News, 7/2/2004). The companies will "continue to work together on the discovery of other RNAi therapeutics for the treatment of ocular diseases," Maraganore noted in a statement released this week.
With its AMD program on the shelf, Alnylam has turned its attention to its RSV drug candidate, called ALN-RSV01, which is now expected to be submitted to the US Food and Drug Administration under an investigative new drug application before the end of the year. Previously, Alnylam had been projecting that an IND for an RSV candidate would be filed in the first half of 2006.
"We are able to move our therapeutic candidate into human clinic trials ahead of schedule," Maraganore said, adding that "based on our interactions with regulatory authorities, we believe we have a clear path forward to conduct a phase I safety study."
According to Alnylam, recent data, which was presented at the RSV Symposium 2005 in the UK, indicate that ALN-RSV01 "selectively and potently silences the highly conserved RSV N gene, which encodes a previously non-druggable protein target required for viral replication," both in vivo and in vitro.
"Intranasally delivered ALN-RSV01 specifically inhibits RSV replication in animals and is active in the prevention and treatment of RSV infection," Alnylam said. Additionally, no significant toxicities associated with the drug have been seen to date, the company said.
— Doug Macron ([email protected])