close

Clinical Trials

Date: 2017-06-26

Type of information: Presentation of results at a congress

phase: observational

Announcement: presentation of results at the 2017 International Congress on Porphyrins and Porphyrias (ICPP)

Company: Alnylam Pharmaceuticals (USA - MA)

Product: givosiran (ALN-AS1)

Action mechanism:

  • RNAi. Givosiran (ALN-AS1) is a subcutaneously administered, investigational RNAi therapeutic that utilizes Alnylam's proprietary Enhanced Stabilization Chemistry (ESC)-GalNAc-siRNA conjugate delivery platform. This RNAi is targeting aminolevulinic acid synthase 1 (ALAS1). ESC-GalNAc-siRNA conjugates are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor, and enable subcutaneous dosing with increased potency and durability and a wide therapeutic index. In pre-clinical studies, multi-dose administration of a GalNAc-siRNA targeting ALAS-1 led to rapid, dose-dependent, and long-lasting knockdown of the ALAS-1 mRNA in non-human primates, with an ED50 of approximately 1.25 mg/kg. Further, in a rat model of AIP, ALN-AS1 administration at doses as low as 2.5 mg/kg resulted in a complete blunting of phenobarbital-induced over-production of ALA and PBG, the toxic heme intermediates in AIP. Pre-clinical studies with RNAi therapeutics targeting ALAS1 have been published by Alnylam and collaborators previously (Yasuda et al., Proc Natl Acad Sci USA 2014;111(21):7777-7782).
  • In January 2014, Alnylam and Genzyme, a Sanofi company, formed an alliance to accelerate and expand the development and commercialization of RNAi therapeutics across the world. The alliance is structured as a multi-product geographic alliance in the field of rare diseases. Alnylam retains product rights in North America and Western Europe, while Genzyme obtained the right to access certain programs in Alnylam's current and future Genetic Medicines pipeline, including ALN-AS1, in the rest of the world.

Disease: acute hepatic porphyria

Therapeutic area: Rare diseases - Metabolic diseases

Country: Bulgaria, Czechia, Finland, France, Germany, Italy, Netherlands, Norway, Poland, Spain, Switzerland, UK, USA

Trial details:

  • EXPLORE is a prospective, multinational, observational study characterizing the natural history and clinical management of AHP patients with recurrent attacks (3 or more attacks/year) or who receive hemin or gonadotropin-releasing hormone analogue prophylaxis to prevent attacks. The purpose of this study is to characterize the natural history and clinical management of Acute Hepatic Porphyria (AHP) patients with recurring attacks. (NCT02240784)

Latest news:

  • • On June 26, 2017, Alnylam Pharmaceuticals, a leading RNAi therapeutics company, announced the presentation of data from the EXPLORE natural history study at the 2017 International Congress on Porphyrins and Porphyrias (ICPP), being held from June 25 - 28, 2017 in Bordeaux, France .
  •  A total of 112 patients with acute hepatic porphyria (AHP), of which 104 have AIP, were enrolled from 13 countries. Updated 12-month data from EXPLORE demonstrate that patients suffer from both acute attacks and chronic symptoms (64 percent of patients) in between attacks, that together result in a diminished quality of life. The annualized attack rate on study was approximately five attacks/person with a mean attack duration of seven days. The majority of attacks (77 percent) required treatment in the hospital, urgent healthcare facility or with hemin. An analysis of costs associated with AHP and recurrent attacks - the first analysis of its kind in AHP in the U.S. - revealed the average estimated annual expenditure per patient ranges from approximately $400,000 to $650,000 . These analyses only incorporate direct costs, and do not reflect indirect costs, such as the cost associated with lost productivity for both patients and caregivers.

Is general: Yes