Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has filed a Clinical Trial Application (CTA) with the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a Phase I clinical trial with ALN-AT3, a subcutaneously administered RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia, including people with “inhibitors.” Hemophilia is a hereditary disorder caused by genetic deficiencies in various blood clotting factors, resulting in recurrent bleeds into joints, muscles, and other major internal organs. By knocking down AT, ALN-AT3 administration is expected to increase thrombin generation and reduce disease burden, including annualized bleeding rate, severity of bleeding, and requirement for replacement factor or bypass agent, and to potentially improve quality of life. ALN-AT3 is a key program in the company’s “Alnylam 5x15” product development and commercialization strategy, in which the company aims to advance five RNAi therapeutic programs toward genetically validated disease targets into clinical development, including programs in advanced stages, by the end of 2015.
“Hemophilia is characterized by a genetic deficiency in clotting factors that ultimately leads to inadequate thrombin generation and a bleeding disorder. ALN-AT3 aims to correct the hemostatic imbalance in hemophilia by knocking down AT – an endogenous anticoagulant – thus increasing thrombin generation and improving hemostasis, and reducing disease burden. This innovative approach is strongly supported by clinical cases in people with hemophilia who have co-inherited prothrombotic traits, including AT deficiency, and are characterized by a milder bleeding phenotype,” said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President and Chief Medical Officer at Alnylam. “This CTA for ALN-AT3 marks our second for an RNAi therapeutic that utilizes our proprietary GalNAc conjugate delivery platform, which we have now shown to be clinically validated. Our pre-clinical data with ALN-AT3 have demonstrated normalization of thrombin generation and improvement of hemostasis in hemophilia models. We have also demonstrated that ALN-AT3 has a wide therapeutic index in the context of hemophilia. We very much look forward to the continued advancement of ALN-AT3, including the start of our Phase I clinical trial in early 2014 with data from hemophilia subjects expected by the end of that year.”