The US Food & Drug Administration (FDA) has granted an Orphan Drug Designation (ODD) to Alnylam Pharmaceuticals' ALN-AT3 as a therapeutic for the treatment of hemophilia A.

As reported last week, the FDA has also granted ODD to ALN-AT3 for the treatment of hemophilia B. Alnylam is developing ALN-AT3, a subcutaneously administered RNAi therapeutic targeting antithrombin (AT), for the treatment of hemophilia – including hemophilia A, hemophilia B, and hemophilia A or B with “inhibitors” – and other Rare Bleeding Disorders (RBD).

“We are very pleased that the FDA has granted Orphan Drug Designation for ALN-AT3 now for both the treatment of haemophilia A and haemophilia B. As a subcutaneously delivered RNAi therapeutic, we believe it represents an innovative approach for the management of haemophilia and has great potential to make a meaningful impact in the treatment of this often debilitating bleeding disorder,” said Saraswathy (Sara) Nochur, Ph.D., senior vice president, Regulatory Affairs and Quality Assurance at Alnylam. “ALN-AT3 is a key programme in our ‘Alnylam 5x15’ product development and commercialization strategy, and we look forward to advancing this promising RNAi therapeutic into the clinic in the months to come.”

At the recent Congress of the International Society on Thrombosis and Haemostasis, Alnylam presented pre-clinical data demonstrating that ALN-AT3 can normalize thrombin generation and improve hemostasis in hemophilia mice and can fully correct thrombin generation in a non-human primate (NHP) haemophilia “inhibitor” model. ALN-AT3 utilizes the company’s proprietary GalNAc conjugate delivery platform, enabling subcutaneous dose administration. Alnylam plans to file an investigational new drug (IND) application for ALN-AT3 in the fourth quarter of 2013 and initiate a phase I clinical trial in early 2014.

The FDA Office of Orphan Products Development (OOPD) mission is to advance the evaluation and development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions. OOPD provides incentives for sponsors to develop products for rare diseases. The Orphan Drug Designation programme provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/ disorders that affect fewer than 200,000 people in the US.

Hemophilias are hereditary disorders caused by genetic deficiencies of various blood clotting factors, resulting in recurrent bleeds into joints, muscles, and other major internal organs.

Antithrombin (AT, also known as “antithrombin III” and “SERPINC1”) is a liver expressed plasma protein and member of the “serpin” family of proteins that acts as an important endogenous anticoagulant by inactivating factor Xa and thrombin. AT plays a key role in normal hemostasis, which has evolved to balance the need to control blood loss through clotting with the need to prevent pathologic thrombosis through anticoagulation. In haemophilia, the loss of certain procoagulant factors (Factor VIII and Factor IX, in the case of haemophilia A and B, respectively) results in an imbalance of the hemostatic system toward a bleeding phenotype. In contrast, in thrombophilia (e.g., factor V Leiden, protein C deficiency, antithrombin deficiency, amongst others), certain mutations result in an imbalance in the hemostatic system toward a thrombotic phenotype. Since co-inheritance of prothrombotic mutations may ameliorate the clinical phenotype in haemophilia, inhibition of AT defines a novel strategy for improving hemostasis.

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development.

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi.