Clinical Trials

Date: 2017-07-07

Type of information: Initiation of development program

phase: 3

Announcement: initiation of development program

Company: Alnylam Therapeutics (USA - MA), Sanofi (France)

Product: fitusiran (SAR439774 - ALN-AT3)

Action mechanism:

  • RNAi. ALN-AT3 is a subcutaneously administered RNAi therapeutic that comprises an siRNA conjugated to a triantennary N-acetylgalactosamine (GalNAc) ligand. GalNAc-siRNA conjugates are a proprietary, clinically validated delivery platform and are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor. Pre-clinical studies have shown that subcutaneous administration of ALN-AT3 can normalize thrombin generation and improve hemostasis in hemophilia mice and fully correct thrombin generation in a non-human primate (NHP) hemophilia “inhibitor” model.
  • A single subcutaneous dose of ALN-AT3 that resulted in plasma AT reduction of approximately 90% led to normalization of thrombin generation and improvement in hemostasis in hemophilia mice. In wild type NHPs, repeat dosing with ALN-AT3 resulted in potent, titratable, and reversible silencing of plasma AT. Weekly subcutaneous doses of 0.50 mg/kg resulted in 90% AT knockdown, while an ED50 knockdown was achieved at a dose as low as 0.125 mg/kg. Furthermore, in an NHP “inhibitor” model, in which a hemophilia A (HA) phenotype was induced via administration of a polyclonal anti-factor VIII antibody, ALN-AT3-treated animals showed the expected level of AT knockdown but also showed a statistically significant (p<0.01) dose-dependent increase in thrombin generation, fully restoring this hemostatic parameter back to normal levels.
  • • On November 14, 2016, pursuant to the companies' global alliance signed in January 2014 , Sanofi Genzyme elected to opt in to co-develop and co-commercialize fitusiran, for the treatment of hemophilia and rare bleeding disorders, in the United States , Canada and Western Europe .

Disease: hemophilia A and B with or without inhibitors

Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases


Trial details:

Latest news:

  • • On July 7, 2017, Alnylam and Sanofi Genzyme announced the initiation of the ATLAS Phase 3 clinical program for fitusiran. The global, multicenter program is designed to evaluate the safety and efficacy of fitusiran in three separate trials, including patients with hemophilia A and B with or without inhibitors and patients receiving prophylactic therapy.
  • The three ATLAS studies are designed to evaluate the safety and efficacy of fitusiran across a spectrum of patients living with hemophilia. They are expected to enroll approximately 250 patients across three separate trials conducted at over 100 clinical centers around the world.
  • ATLAS-PPX is an open-label, one-way crossover study designed to enroll approximately 100 patients with hemophilia A or B with or without inhibitors receiving prophylaxis therapy as prior standard of care. In this study, patients will receive standard of care prophylaxis for six months and then transition to fitusiran treatment for seven months. The ABR will be prospectively measured in both periods. The study's primary endpoint is the ABR in the fitusiran period and in the factor/bypassing agent prophylaxis period. Key secondary endpoints include the annualized spontaneous bleeding rate, annualized joint bleeding rate, and quality of life as measured by the Haem-A-QOL score.
  • Top-line data from the ATLAS trials are expected in mid-to-late 2019.

Is general: Yes