A major obstacle facing Sanofi and Alnylam’s haemophilia therapy fitusiran has been removed, after the FDA lifted a clinical hold imposed on the programme in September.
The RNA interference drug, which targets antithrombin (AT), can now resume phase II and III trials in patients with haemophilia A and B without inhibitors, which were suspended after one patient in an open-label phase II trial with haemophilia A suffered a fatal blood clot.
The two companies developed a plan to mitigate the risk of thrombosis in other patients and submitted it to the FDA for consideration, including the use of reduced doses of replacement factor or bypassing agent to treat breakthrough bleeding, which was accepted by the US regulator last month.
The resumption of the ATLAS pivotal trials is a boost to Sanofi – which highlighted the drug in its R&D day last week, saying it had the potential to be of use to 140,000 patients in its licensed territories – but particularly for Alnylam which has seen its RNAi platform come under scrutiny in recent months.
The company recently abandoned one of its gene-silencing drugs – revusiran for the rare disease hereditary ATTR amyloidosis with cardiomyopathy – although its new lead program patisiran for ATTR plus polyneuropathy remains on track and hit its targets in a phase III trial reported in September – and according to some analysts seems to have outperformed a rival therapy from Ionis Pharma.
Patisiran – also partnered with Sanofi as part of a longstanding collaboration between the two companies – was filed with the FDA last week and is due to be submitted in Europe early next year. Under the terms of that alliance the two companies will jointly commercialise fitusiran in the US, Canada and Western Europe, while Sanofi will hold exclusive rights to the drug in the rest of the world.
“Fitusiran holds the potential to help improve the lives of people living with haemophilia,” said Akin Akinc, who is leading the development of the drug at Alnylam.
“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end.”
If approved, fitusiran will launch into a market already addressed in part by Roche’s Hemlibra (emicizumab-kxwh) which was approved by the FDA last month to prevent or reduce bleeding episodes in patients with haemophilia A who have developed inhibitors. Hemlibra has been tipped to become a $1.5bn product by some analysts.