In a release, the Company noted:
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 to have received Orphan Drug Designation from the
At the recent
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. Hemophilia A is defined by loss-of-function mutations in factor VIII, and there are greater than 40,000 people in the U.S. and E.U. Hemophilia B, defined by loss-of-function mutations in factor IX, affects greater than 9,500 people in the U.S. and E.U. Other Rare Bleeding Disorders (RBD) are defined by congenital deficiencies of other blood coagulation factors, including Factors II, V, VII, X, and XI, and there are about 1,000 people worldwide with a severe bleeding phenotype. Standard treatment for people with hemophilia involves replacement of the missing clotting factor either as prophylaxis or on-demand therapy. However, as many as one third of people with hemophilia A will develop an antibody to their replacement factor - a very serious complication; these 'inhibitor' subjects become refractory to standard replacement therapy. There exists a small subset of people with hemophilia who have co- inherited a prothrombotic mutation, such as factor V Leiden, antithrombin deficiency, protein C deficiency, and prothrombin G20210A. People with hemophilia that have co-inherited these prothrombotic mutations are characterized as having a later onset of disease, lower risk of bleeding, and reduced requirements for factor VIII or factor IX treatment as part of their disease management. There exists a significant need for novel therapeutics to treat hemophilia and RBD.
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 hemophilia, the loss of certain procoagulant factors (Factor VIII and Factor IX, in the case of hemophilia 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 hemophilia, inhibition of AT defines a novel strategy for improving hemostasis.
RNAi (RNA interference) is a revolution in biology, representing an understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi.
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In a release, the Company noted: