Alnylam Pharmaceuticals, Inc. and Sanofi Genzyme announced positive results from an ongoing Phase 2 open label extension (OLE) study with fitusiran in patients with hemophilia A and B, both with or without inhibitors. Details from the study were presented at 26th International Society on Thrombosis and Haemostasis Meeting, July 8-13, 2017, in Berlin, Germany.
Fitusiran is a subcutaneous therapy (administered under the skin) that employs small interfering RNA (siRNA) technology to target antithrombin (AT), a liver-generated clotting protein that plays a key role in the regulation of blood clots. siRNA molecules are segments of RNA (ribonucleic acid) that block or “silence” the activity of certain genes through RNA interference, a natural biological process common in plants and mammals. Fitusiran works by silencing the gene responsible for AT, which inhibits the protein’s anticoagulant function. This then compensates for the imbalance caused by deficiencies in other clotting proteins, such as factor VIII (hemophilia A) or factor IX (hemophilia B).
According to an Alnylam press release, the latest Phase 2 study showed that the safety and tolerability associated with fitusiran “remains encouraging,” with no thromboembolic events, including during co-administration of replacement factor or bypassing agents. The majority of adverse events were mild or moderate in severity, with the most common related to mild and temporary injection site reactions. In addition, once-monthly injections of fitusiran achieved lowering of AT, increases in thrombin generation, and reductions in the median estimated annualized bleeding rate in patients with and without inhibitors. In light of these results, the companies announced the initiation of the ATLAS Phase 3 program for fitusiran in patients with hemophilia A and B with or without an inhibitor
The results of the companies Phase 1 clinical trial results demonstrating an encouraging preliminary safety and tolerability profile and initial evidence that monthly subcutaneously administered fitusiran lowered AT levels and increased thrombin generation in patients with hemophilia A and B without inhibitors were published online by The New England Journal of Medicine. The journal will also publish the study in their September 7th print issue.
“With up to 20 months of dosing in patients, we are encouraged by the results from our fitusiran clinical studies presented at the ISTH meeting today, demonstrating what we believe to be promising support for further clinical development,” said Akin Akinc, PhD, Alnylam’s Vice President and General Manager, Fitusiran. “We’re also pleased to have announced initiation of our ATLAS Phase 3 program just last week, where the safety and efficacy of fitusiran will be evaluated and where we expect initial results in mid-to-late 2019.”
Source: Alnylam press release dated July 10, 2017
