FDA Approves Sanofi’s siRNA Therapy Fitusiran for the Treatment of Hemophilia A and B
The product is marketed under the name Qfitlia.
This is a developing story and will be updated with new information as it becomes available.
The FDA has approved Sanofi's fitusiran, an siRNA therapeutic intended to lower antithrombin, for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients aged 12 years and older with hemophilia A or hemophilia B, with or without factor VIII or IX inhibitors.1 The therapy will be marketed under the name Qfitlia.
Fitusiran is specifically expected to increase the production of thrombin by decreasing levels of antithrombin, with the goal of hemostasis restoration. The FDA's decision was made based on data from the ATLAS clinical development program, which includes the completed phase 3 clinical trials ATLAS-INH (NCT03417102), ATLAS-A/B (NCT03417245), and ATLAS-PPX (NCT03549871) and the ongoing phase 3 clinical trials ATLAS-NEO (NCT05662319), ATLAS-PEDS (NCT03974113), and ATLAS OLE (NCT03754790). Notably, the FDA also approved Siemens Healthineers’ companion diagnostic for fitusiran, refereed to as Innovance Antithrombin Assay, which is to be used to assess antithrombin levels in patients who have been prescribed fitusiran
“Qfitlia delivers the fewest doses of any prophylactic therapy in hemophilia, and its unique mechanism allows it to be used to treat all types of hemophilia, including with inhibitors and hemophilia B, where unmet medical needs remain," Guy Young, MD, the director of the Hemostasis and Thrombosis Center at Children's Hospital, Los Angeles, said in a statement.1 "By targeting antithrombin, which can be reliably measured with an FDA-cleared blood assay, Qfitlia is proven to help rebalance hemostasis and improve bleed rates and protection.”
In the ATLAS program, fitusiran decreased annualized bleeding rates (ABR) by 71% in patients without inhibitors in comparison to clotting factor concentrate on-demand (estimated mean: ABR 9.0 versus 31.4; P < .0001) and by 73% in comparison to bypassing agent on-demand for patients with inhibitors (estimated mean: ABR 5.1 versus 19.1; P = .0006). Furthermore, in ATLAS-OLE, a median ABR of 3.8 (IQR: 0.0–11.2) was seen in patients without inhibitors and a median ABR of 1.9 (IQR: 0.0–5.6) was seen in patients with inhibitors. Additionally, in ATLAS-OLE, it was noted that almost half of the patients had 1 or fewer bleeds, with 31% having 0 bleeds and 47% having 0 or 1 bleeds. In patients without inhibitors in ATLAS-OLE, a 1.9 median observed annualized spontaneous bleeding rate [interquartile range (IQR): 0.0-7.5] was seen, and in patients with inhibitors in ATLAS-OLE, a 1.9 median observed annualized spontaneous bleeding rate (IQR: 0.0-3.7) was also seen.
With regard to safety, Sanofi stated that the most common adverse events (AEs) observed with fitusiran, with an incident of more than 10%, have been viral infection, nasopharyngitis, and bacterial infection. The company notes that thrombotic events, acute and recurrent gallbladder disease, and hepatotoxicity constitute potential significant AEs that could result from treatment with fitusiran.
“Current treatment options can make people with hemophilia feel they need to choose between effective bleed control and convenient dosing schedules, leading to trade-offs when it comes to disease management," Phil Gattone, the
president and CEO of the National Bleeding Disorders Foundation, added to the statement.1 "Qfitlia takes a novel approach to providing protection for people living with hemophilia while reducing the frequency of dosing for patients and their families.”
CGTLive®'s sister site, HCPLive®, previously spoke with Steven W. Pipe, MD, a professor of pediatric hematology/oncology at CS Mott Children’s Hospital, who presented data from ATLAS-OLE at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024, in San Diego, California.2 In the interview at the conference, Pipe gave his view on fItusiran based on the data presented.
"I think the conclusion I take from this is that fitusiran is a highly effective prophylactic agent and the modulation of thrombin generation allows for achieving effective bleed control with substantially lower doses of factor and bypassing agents, as well as fewer infusions," Pipe told HCPLive®. "This is just an overall better patient experience because if you're on an effective prophylactic agent, you're probably not infusing regularly anymore. The fact that you could look forward to, if you did have a breakthrough bleed, an effective bleed control in most patients, with just a single infusion at a much reduced dose, I think is a really great outcome for this trial."
