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Alnylam Presents New Data on Fitusiran at EAHAD

– New Phase 1 Results Demonstrate Effective Bleed Management with Replacement Factor and Bypassing Agents During Fitusiran Administration –

– Stability Study Results Support a Greater than Two Year Product Shelf-Life at Room Temperature Storage Conditions –

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company today announced new results from an exploratory analysis of its Phase 1 study with fitusiran, an investigational RNAi therapeutic, in patients with hemophilia A or B with or without inhibitors. This analysis of bleed management during fitusiran administration showed that breakthrough bleeds were effectively managed with replacement factors or bypassing agents, with no thromboembolic events. Additionally, results presented from stability studies of fitusiran support a greater than two-year shelf life at room temperature storage conditions and demonstrated resistance to thermal stress, favoring real world handling of the final drug product. These data were presented at the 10th Annual Congress of the European Association of Haemophilia and Allied Disorders (EAHAD) held February 1 – 3, 2017 in Paris, France.

New analyses examined 21 total bleed events in 41 patients treated with fitusiran, after achieving greater than 75 percent antithrombin lowering. This analysis found that dosing of agents was generally within the normal dose range for replacement Factor VIII and Factor IX as well as for the bypassing agent rFVIIa, while at the lower end of the range for the bypassing agent aPCC. Treatment of all breakthrough bleed events resulted in successful hemostasis without any thromboembolic events.

“We are encouraged by this new analysis which provides evidence that breakthrough bleeds occurring in patients treated with fitusiran can be effectively managed with both replacement factor and bypassing agents, with no thromboembolic events. These data, combined with positive recent clinical results, continue to support the potential of fitusiran as a once-monthly subcutaneous investigational medicine for the management of hemophilia,” said Akin Akinc, Ph.D., Vice President and General Manager, Fitusiran. “Furthermore, data continue to support the robust stability profile of fitusiran, potentially facilitating treatment in regions where cold chain storage requirements represent a challenge to patients’ access to effective therapies. We continue to advance toward the start of our ATLAS Phase 3 clinical program in early 2017.”

An evaluation of fitusiran at refrigerated (i.e., 5ºC), customary room temperature (i.e., 25ºC/60 percent relative humidity) and at accelerated aging conditions (i.e., 40ºC) demonstrated a robust stability profile, with all key quality attributes predicted to be retained at both refrigerated and room temperature conditions for at least 24 months. Further, fitusiran has shown resistance to thermal stress and cyclic temperature fluctuations that may occur during real world storage and handling of the drug product. Consequently, the stability profile of fitusiran could enable convenient transportation and storage, including in parts of the world where cold chain delivery is a challenge.

To view the fitusiran clinical results described in this press release, please visit

About Fitusiran

Fitusiran is a subcutaneously administered, investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia A and B and rare bleeding disorders (RBD) currently in early stage clinical development. Fitusiran is designed to lower levels of AT with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding in patients with hemophilia and RBD. AT, also known as "antithrombin III" and "SERPINC1" is a liver-expressed plasma protein and member of the "serpin" family of proteins that acts by inactivating thrombin and other coagulation factors. AT plays a key role in normal hemostasis by helping to limit the process of fibrin clot formation. However, in hemophilia, insufficient thrombin generation results in impaired fibrin clot formation. Lowering AT in the hemophilia setting may promote the generation of sufficient levels of thrombin needed to form an effective fibrin clot and prevent bleeding. This rationale is supported by human genetic data suggesting that co-inheritance of thrombophilic mutations, including AT deficiency, may ameliorate bleeding in hemophilia. Lowering of AT is a unique and innovative strategy for restoring hemostasis in people with hemophilia. Fitusiran utilizes Alnylam's ESC-GalNAc conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index.

About Fitusiran Phase 1 Study

The ongoing Phase 1 trial of fitusiran is being conducted in the United States, Bulgaria, Russia, Switzerland, and the U.K. as a single- and multi-dose, dose-escalation study comprised of four parts. Part A – which is complete – was a randomized, single-blind, placebo-controlled, single-dose, dose-escalation study (N=4 per cohort; 3:1 randomization of fitusiran:placebo) in healthy volunteers. This part of the study was completed after the first dose cohort received a single subcutaneous dose of fitusiran at 30 mcg/kg. Part B of the study – which is also complete – was an open-label, multi-dose, dose-escalation study that enrolled 12 patients with severe hemophilia A or B. Patients in Part B received three weekly subcutaneous injections of fitusiran at doses of 15, 45, or 75 mcg/kg. Part C of the study – which has completed dosing – is an open-label, multi-dose, dose escalation study that enrolled 18 patients with moderate or severe hemophilia A or B without inhibitors. Twelve patients in Part C received three monthly subcutaneous doses of fitusiran at doses of 225, 450, 900, or 1800 mcg/kg. In addition, six patients in Part C received three fixed monthly subcutaneous doses of fitusiran at 80 mg. Part D was designed to enroll up to 18 patients with inhibitors. Patients in Part D received 3 fixed monthly subcutaneous doses of fitusiran at 50 mg or 80 mg. The primary objective of Parts B, C, and D of the study is to evaluate the safety and tolerability of multiple doses of subcutaneously administered fitusiran in patients with hemophilia, with and without inhibitors. Secondary objectives include assessment of clinical activity as determined by lowering of circulating AT levels and increase in thrombin generation at pharmacologic doses of fitusiran. In addition, exploratory analyses of bleeding are being performed. In the U.K., enrollment has been aided by the Southern Academic Coagulation Consortium (SACC).
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