Fitusiran, also known as ALN-AT3SC, is an RNAi therapeutic agent that targets a protein called antithrombin — which inhibits blood clotting — while increasing production of the protein thrombin, which aids clotting. Fitusiran helps regulate the clotting response to prevent bleeding episodes in patients with hemophilia A or B.
In 2014, Alnylam Pharmaceuticals and Sanofi Genzyme partnered to promote RNAi therapeutics for rare genetic diseases. This type of therapy targets molecules called messenger ribonucleic acids (mRNAs). Fitusiran binds the mRNA of antithrombin, halting its production.
Previous data from the Phase 1 clinical trial of fitusiran showed that a single monthly injection reduced the levels of the antithrombin protein and restored the balance of production of clotting elements in adult patients with hemophilia A or B.
Last September, Alnylam suspended patient dosing in all ongoing trials with fitusiran after a patient with hemophilia A died of swelling in the brain in a Phase 2 trial. But, in December, the U.S. Food and Drug Administration (FDA) lifted the hold on clinical studies with fitusiran after the trial’s protocol was amended to better mitigate risks. With the FDA’s green light, Alnylam and Sanofi will now enroll patients in the ATLAS Phase 3 program throughout 2018.
The ATLAS Phase 3 program includes three separate trials that will recruit patients with hemophilia A and B with or without inhibitors and patients receiving prophylactic, or preventive, therapy.
Alnylam Pharmaceuticals’ corporate goals for 2018 also include continuing clinical development of RNAi therapeutics for several other genetic disorders. Among the investigational therapies are patisiran and ALN-TTRsc02 for hereditary ATTR amyloidosis, a rare disease caused by a genetic mutation that results in the buildup of misfolded transthyretin protein, and givosiran for acute hepatic porphyrias.
“In the year ahead, we look forward to the potential global commercial launch of patisiran, the first-ever RNAi therapeutic to enter the market, marking the birth of a whole new class of medicines with the potential to transform the treatment of diseases with high unmet need,”John Maraganore, PhD, chief executive officer at Alnylam, said in a press release.
“Together with the advancements made in our other late-stage programs, we now look forward to our transition from a development-stage company toward a multi-product, global commercial-stage biopharmaceutical company with a deep and sustainable pipeline and research engine,” he added.