- Interim results from an ongoing Phase 2 open-label extension study assessing Alnylam's (NASDAQ:ALNY) fitusiran in patients with hemophilia A or B without inhibitors showed clinically meaningful activity. The data were presented today at the 58th American Society of Hematology (ASH) annual meeting in San Diego.
- As of the October 6 data cut-off, a total of 16 patients had received once-monthly subcutaneous doses of fitusiran in two dosage arms: 50 mg (n=8) and 80 mg (n=8) for up to 14 months. All were previously enrolled in a Phase 1 trial during which they received three weekly or three monthly subcutaneous doses ranging from 45 mcg/kg to 1800 mcg/kg.
- Both dosage levels lowered average antithrombin (AT) by ~80% with average increases in thrombin approaching the lower end of the normal range in healthy people who participated in Part A of the Phase 1. In an exploratory post hoc (after the fact) analysis, treatment with fitusiran lowered median annualized bleed rate (ABR) to 1.0 from 4.0 over a median observation period of 5.7 months. 50% (n=8/16) of subjects reported zero bleeds and 69% (n=11/16) experienced zero spontaneous bleeds.
- Fitusiran was generally well-tolerated over the study period (up to 14 months of continuous treatment). All adverse events (AEs) were mild to moderate. The most common were injection site reactions (25%). Elevations in a liver enzyme called ALT (biomarker for organ stress) greater than 3x the upper limit of normal (ULN) without concurrent elevations in bilirubin greater than 2x ULN were observed in three (19%) patients, all with a history of hepatitis C virus infection. There were no drug-related serious adverse events, no AE-related discontinuations, no thromboembolic events and no laboratory evidence of pathologic clot formation through the cut-off date.
- A Phase 3 study should commence in early 2017. The product candidate is being co-developed and will be co-commercialized with Sanofi Genzyme (SNY).
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Fitusiran is an investigational small interfering RNA therapeutic targeting antithrombin (AT), a naturally occurring protein that interferes with certain enzymes involved in blood clotting. Lowering AT promotes the generation of an enzyme called thrombin which plays an essential role in clotting.