Alnylam Pharmaceuticals, Inc., a biopharmaceutical company, discovers, develops, and commercializes novel therapeutics based on RNA interference. The company’s clinical development programs include Patisiran and Revusiran, which are in Phase III clinical trials for the treatment of transthyretin amyloidosis (ATTR); ALN-TTRsc02, an investigational RNAi therapeutic targeting TTR for the treatment of various forms of ATTR amyloidosis; Fitusiran, an investigational RNAi therapeutic that is in Phase I clinical trial for the treatment of hemophilia and rare bleeding disorders; ALN-CC5, which is in Phase I/II clinical trial for the treatment of complement-mediated diseases; and ALN-AS1 for the trea...
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Founded in 2002
Alnylam Pharmaceuticals, Inc. Announces Management Changes
Jan 3 17
Alnylam Pharmaceuticals, Inc. announced that David-Alexandre "DA" Gros, M.D., Senior Vice President and Chief Business Officer, plans to leave the company for personal reasons. His resignation will be effective January 6, 2017, and the company will initiate a search for his replacement. Additionally, the Company announced the promotion of Pushkal Garg, M.D., Senior Vice President, Clinical Development, to the role of Chief Medical Officer, reporting to Akshay Vaishnaw, Executive Vice President of R&D. In his promotion to Chief Medical Officer, Dr. Garg will be responsible for clinical development at Alnylam, leading clinical research, clinical operations, biometrics, and medical writing functions. He will also join the company’s Management Board. Dr. Garg joined Alnylam in late 2014 with over 15 years of experience in early and late-stage clinical drug development, including at Bristol-Myers Squibb and Millennium Pharmaceuticals.
Alnylam Pharmaceuticals, Inc. Presents at 35th Annual JP Morgan Healthcare Conference, Jan-09-2017 09:00 AM
Jan 3 17
Alnylam Pharmaceuticals, Inc. Presents at 35th Annual JP Morgan Healthcare Conference, Jan-09-2017 09:00 AM. Venue: Westin St. Francis Hotel, 335 Powell Street, San Francisco, CA 94102, United States. Speakers: John M. Maraganore, Chief Executive Officer and Executive Director.
Alnylam Pharmaceuticals, Inc. Announces New Results from Phase 1/2 Study of ALN-CC5 in Patients with Paroxysmal Nocturnal Hemoglobinuria
Dec 5 16
Alnylam Pharmaceuticals, Inc. presented new results from Part C of its Phase 1/2 clinical trial with ALN-CC5, a subcutaneously administered investigational RNAi therapeutic targeting complement component 5 (C5) for the treatment of complement-mediated diseases, in a poster presentation at the 58th Annual Meeting of the American Society of Hematology (ASH), held December 3 – 6, 2016 in San Diego, California. Part C evaluated the tolerability and clinical activity of ALN-CC5 in patients (N=6) with paroxysmal nocturnal hemoglobinuria (PNH), a rare hematologic disease where acquired mutations in the PIG-A gene lead to complement-mediated destruction of red blood cells (RBC). In an exploratory analysis, ALN-CC5 was evaluated in combination with eculizumab, an approved anti-C5 monoclonal antibody used for treatment of PNH. New results show that ALN-CC5-mediated knockdown of serum C5 has the potential to enable effective sparing of eculizumab in patients with PNH. These data further support development of ALN-CC5 to potentially reduce the dose level and frequency of eculizumab in patients with PNH, and to improve disease control in patients with an inadequate response to eculizumab. The company also announced that Sanofi Genzyme has decided not to exercise its opt-in right for the development of ALN-CC5 in territories outside of the United States, Canada and Western Europe, providing Alnylam with full global control of the program for further development and potential commercialization. In the Phase 1/2 study, a total of 6 patients with PNH were enrolled in Part C of the trial, including patients who were eculizumab naive (N=3) and patients who were receiving background eculizumab therapy (N=3). ALN-CC5 was administered at weekly doses of 200 or 400 mg for 2 to 16 weeks and achieved C5 knockdown of up to 98% and residual serum C5 levels less than 1 microgram per milliliter (mcg/mL). Upon completion of ALN-CC5 dosing and in the setting of ongoing ALN-CC5 pharmacology, investigators elected to treat patients with 600 mg or 900 mg of eculizumab every 4 weeks, enabling an exploratory analysis of the potential of ALN-CC5 to reduce the dose and frequency of eculizumab. As of the data transfer date of October 13, 2016, results showed that PNH patients who had previously been naive to eculizumab (N=3) achieved sustained control of disease hemolysis with normalization of lactate dehydrogenase (LDH) to less than or at approximately 1.5 times upper limit of normal (ULN) for up to 6 months while on a spared eculizumab regimen of 600 mg every 4 weeks. For patients who entered the study on background eculizumab (N=3), effective disease control with normalization of LDH to less than or at approximately 1.5 times ULN was achieved for up to 5 months while on a spared once-monthly regimen of 900 mg eculizumab. Using an assay for eculizumab plasma levels, both sparing regimens achieved stable eculizumab trough levels greater than 100 mcg/mL during the 5 to 6 month period. In aggregate, these results support the potential to achieve effective management of hemolysis in PNH during ALN-CC5 pharmacology with a spared eculizumab dosing regimen representing a 50% to 67% reduction in dose and a 2-fold extension of dose interval relative to the labeled eculizumab maintenance dose and regimen. The Phase 1/2 trial of ALN-CC5 was conducted in three parts. Parts A and B were randomized (3:1, drug:placebo), double-blind, placebo-controlled, SAD and MAD studies, respectively, which enrolled 56 healthy adult volunteers. These parts of the study were designed to evaluate safety and tolerability of single and multiple subcutaneous doses of ALN-CC5. Additional objectives included clinical activity as measured by knockdown of serum C5 and levels of residual C5, and by effects on inhibition of serum complement activity, including measurements of CAP and CCP activity, as well as serum sheep red blood cell hemolytic activity. A total of 5 SAD cohorts were enrolled in the study, with fixed doses ranging from 50 to 900 mg. A total of 6 MAD cohorts were enrolled in the study with fixed doses of 100, 200, 400, or 600 mg, where healthy adult volunteers received subcutaneous doses of ALN-CC5 or placebo for up to 14 weeks. Part C is an open-label, multi-dose study that enrolled 6 patients with PNH, to assess safety, tolerability, and clinical activity of ALN-CC5, administered for up to 16 weeks. This part of the study included an exploratory evaluation of ALN-CC5 effects on levels of LDH, a measure of endogenous red blood cell hemolysis. ALN-CC5 is an investigational RNAi therapeutic targeting component 5 of the complement pathway (C5), currently in early stage clinical development for the treatment of complement-mediated diseases. The safety and efficacy of ALN-CC5 have not been evaluated by the U.S. Food and Drug Administration or any other health authority. The complement system plays a central role in immunity as a protective mechanism for host defense, but its dysregulation results in life-threatening complications in a broad range of human diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic-uremic syndrome (aHUS), myasthenia gravis, neuromyelitis optica, and membranous nephropathy, amongst others. C5, which is predominantly expressed in liver cells, is a genetically and clinically validated target; loss of function human mutations are associated with an attenuated immune response against certain infections and intravenous anti-C5 monoclonal antibody (mAb) therapy has demonstrated clinical activity and tolerability in a number of complement-mediated diseases. A subcutaneously administered RNAi therapeutic that silences C5 represents a novel approach to the treatment of complement-mediated diseases. ALN-CC5 utilizes Alnylam's ESC-GalNAc conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index. GalNAc-siRNA conjugates are a proprietary Alnylam delivery platform and are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor. Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology enables subcutaneous dosing with increased potency and durability, and a wide therapeutic index. This delivery platform is being employed in nearly all of Alnylam's pipeline programs, including programs in clinical development. 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.