Alnylam pushes for PhI trial of orphan hemophilia RNAi drug

Alnylam ($ALNY) is forging ahead with another of its RNAi candidates, this time heading overseas with an application to begin a clinical trial in the U.K. for its hemophilia A and B antithrombin-targeting treatment.

Alnylam's ALN-AT3 is designed to "knock down" the gene target antithrombin, increasing thrombin generation to ease the blood-clotting factors that lead to hemophilia. Back in August, the Cambridge, MA, company won orphan designation from the FDA for the drug, expecting to begin a Phase I trial in the U.S. by 2014. This week's application to U.K. authorities would allow it to move forward with that plan.

It's the delivery of RNAi that gives many candidates in the arena trouble, though, and Alnylam's platform is a leader so far in that regard. Executive Vice President and Chief Medical Officer Akshay Vaishnaw weighed in to FierceDrugDelivery.

"In the early years of developing RNAi therapeutics, a challenge to the viability of RNAi as a therapeutic modality was delivery--i.e., getting the siRNA into the cell so that it could trigger the RNAi mechanism," Vaishnaw wrote in an email. "With Alnylam's development of our GalNAc-siRNA conjugate delivery approach, we are able to subcutaneously administer our drugs, which may allow for improved administration of therapeutics for people with hemophilia, who are currently limited to IV administration for their treatments."

In preclinical studies, ALN-AT3 showed improved hemostasis in hemophilia models and fully correct thrombin generation in large animal models, Vaishnaw said.

And as far as its delivery conjugates go, Alnylam has several other candidates in the works making use of the technology, fueling its ambition to advance at least 5 of them to clinical trials by 2015. Its furthest along is a treatment for TTR-mediated amyloidosis, which it expects to enter Phase III by the end of the year.

"Alnylam's advances with GalNAc-siRNA conjugates clearly extend the potential of RNAi therapeutics," Vaishnaw said, "complementing the clinical success we have already achieved in systemic delivery with lipid nanoparticles."

- here's the release