An experimental hemophilia drug cut bleeding episodes by 90% in patients who took it when compared to those given standard treatments in a late-stage clinical trial, according to data unveiled at a medical meeting Tuesday.
The data come from a trial of fitusiran, an RNA-modulating drug, in both hemophilia A and hemophilia B patients who have not developed inhibitors — a type of immune system response that reduces the effectiveness of standard treatments. Over a period of more than six months, 40 of the 79 patients given fitusiran didn't have bleeds that required treatment with so-called factor replacement therapies, compared with an annual bleed rate of 21.8 for those receiving typical drugs.
The results were released at the annual meeting of the American Society of Hematology, or ASH. Earlier in the same meeting, developer Sanofi outlined full data from a trial in hemophilia patients with inhibitors. The trial had nearly identical findings to the non-inhibitor study in terms of bleeding reduction, when compared to patients receiving other treatments on demand.
Fitusiran promises to help people with hemophilia reduce their dependence on factor replacement therapies, which treat and prevent bleeding incidents through frequent infusions of proteins missing from their bloodstreams. Sanofi, however, could launch the drug after gene therapies from BioMarin Pharmaceutical and UniQure get to market. As potential one-time treatments, each of those therapies could prove tough competition.
Physicians may also be reluctant to switch treatments for patients who are stable on factor replacement therapies, providing another obstacle to uptake of fitusiran.
What Sanofi hopes to achieve is a single drug that can be used broadly in patients with hemophilia A or B, and in those severely ill patients who develop inhibitors to factor replacement therapies.
Moreover, the company claims that a subcutaneous shot given once monthly will be attractive to patients, who currently must receive intravenous infusions multiple times a week in the case of factor replacement therapies, or as often as once a week with another approved drug, Roche's Hemlibra.
"If we look on a global basis, approximately 70% of patients across the world do not have any access to regular factor replacement therapy," Steven Pipe, a University of Michigan medical professor, said in a press briefing outlining the new data in non-inhibitor patients.
But that promise is balanced against some safety concerns over blood clots. Clinical work was suspended in 2017 following a patient death due to blood clots. And in 2020, Sanofi paused dosing again after a non-fatal blood clotting incident.
In response, Sanofi instituted lower doses and dose adjustments based on patient monitoring in clinical trials, which could make the drug less convenient to use. The delays and adjustments have slowed its progress and now Sanofi won't ask the Food and Drug Administration to approve it until 2024. (Fitusiran is licensed from Alnylam Pharmaceuticals, which shared development with Sanofi until the companies restructured their research alliance in 2018.)
As a result, fitusiran could trail by two years or more a hemophilia A gene therapy from BioMarin and another for hemophilia B from UniQure, both of which are due to be in front of regulators in 2022.
In the trial with patients who haven't developed inhibitors, there were no blood clots among patients given fitusiran. In the inhibitor trial, however, clots were observed in two patients, one of whom had them in three different spots.
Patients given fitusiran also had elevations of liver enzymes, which regulators eye closely because it can be a sign of damage to the organ. In the non-inhibitor trial there were 15 instances of elevated liver enzymes, and in the inhibitor trial there were 11.
Guy Young, director of the hemostasis and thrombosis program at Children's Hospital of Los Angeles, presented the data from the inhibitor population at ASH. Young speculated that the liver enzyme elevations could be caused by the way fitusiran is design to work — by targeting a protein called anti-thrombin that's produced in the liver.
"The elevations were pretty modest," he added, however. "None of the patients discontinued the drug due to that."