Fitusiran Curbs Bleeds in Hemophilia A, B With Inhibitors, Data Show
In addition, data from other studies indicated that when used long-term, fitusiran was able to improve the quality of life of hemophilia A patients with or without inhibitors.
These findings will be presented at the American Society of Hematology Annual Meeting, to be held Dec. 11–14.
Hemophilia A and B are bleeding disorders characterized by ineffective blood clotting and excessive bleeding due to the lack of specific blood clotting proteins.
Developed by Alnylam Pharmaceuticals in collaboration with Sanofi, fitusiran is an investigational RNA interference treatment for people with hemophilia A or B, with and without inhibitors (neutralizing antibodies that may render conventional replacement therapies ineffective).
The therapy is designed to block the activity of a protein called antithrombin, which normally inactivates thrombin and blood clotting.
The Phase 3 ATLAS-INH trial (NCT03417102) was an open-label study to evaluate the safety and efficacy of fitusiran in hemophilia A and B patients, 12 or older, with inhibitors.
Data from the now-completed trial will be presented at a plenary scientific session at the annual meeting, under the title “Efficacy and Safety of Fitusiran Prophylaxis, an siRNA Therapeutic, in a Multicenter Phase 3 Study (ATLAS-INH) in People with Hemophilia A or B, with Inhibitors (PwHI).”
In the study, participants were randomly assigned to receive a once-monthly under-the-skin 80 mg injection of fitusiran, or to continue receiving on-demand treatment with bypassing agents (BPA) — treatments that do not rely on conventional clotting factors to promote blood clotting and are indicated for hemophilia patients with inhibitors who no longer respond to replacement therapies.
The study’s main goal was to compare the frequency of annual bleeding episodes — measured by the annualized bleeding rate (ABR) — in fitusiran- and BPA-treated patients. Secondary goals included evaluating spontaneous ABR, joint ABR, and health-related quality of life (HRQoL), as assessed by the Haem-A-QoL questionnaire.
Among the 57 participants enrolled in the study (ages 13–63 years), fitusiran significantly reduced ABRs for all bleeds compared with BPA (1.67 vs. 18.07), as well as spontaneous bleeds (0.87 vs. 15.68), and joint bleeds (1.35 vs. 13.76) in both hemophilia A and B patients with inhibitors.
No bleeding events were seen in 25 patients (65.8%) treated with fitusiran.
Preventive treatment with fitusiran was also associated with significant improvements in overall HRQoL compared with on-demand treatment with BPA.
At least one treatment-emergent adverse event was reported in 38 patients who received fitusiran (92.7%) and in 11 (57.9%) participants in the BPA group. In total, 13 treatment-emergent serious adverse events were observed in seven (17.1%) patients in the futisiran group, while a total of eight such events were reported by five BPA-treated patients.
Serious side effects in the fitusiran group included infection, blood in the urine, spinal vascular disorder, thrombosis (blood clot formation), gallbladder inflammation, and asymptomatic COVID-19. One fitusiran-treated patient left the study due to spinal vascular disorder and thrombosis. No deaths were reported.
“In our efforts to support the transformation of therapeutic landscapes, we look forward to presenting our Phase 3 results on fitusiran’s ability to provide protection from bleeds for people with hemophilia A or B with inhibitors,” Dietmar Berger, MD, PhD, chief medical officer at Sanofi, said in a press release.
The team will also present a poster with updated HRQoL data from a six-year Phase 1/2 open-label extension study (NCT02554773) evaluating fitusiran in patients with hemophilia A with or without inhibitors. The poster is titled “Sustained Improvement in Health-Related Quality of Life in Patients with Hemophilia A with or without Inhibitors Treated with Fitusiran Prophylaxis.”
Participants who completed a previous Phase 1 study (NCT02035605), which evaluated the safety and tolerability of fitusiran, were eligible to enter the long-term exposure study where they received fixed monthly doses of 50 mg or 80 mg of fitusiran. HRQoL data were collected every three months.
As of February — the analysis cutoff date — 27 patients (13 with inhibitors and 14 without), with a mean age of 37.3 years before treatment, were given fitusiran for up to a mean of 33.32 months (about 2.8 years).
For the total Haem-A-QoL score and each of the 10 domains, mean improvement changes were seen in all participants, except for the sport and leisure domain, which was higher (worse) in the non-inhibitor group.
For patients with inhibitors, the mean Haem-A-QoL total score dropped by 8.33 points and the physical health domain by 13.21 points (lower scores denoting better HRQoL). For patients without inhibitors, the mean Haem-A-QoL total score dropped by 9.16 points and the physical health domain by 7.14 points.
Results favored a modest trend for better HRQoL in participants without inhibitors.
“Small sample size and outlying results might limit the interpretation,” the team noted. “Further research in HRQoL for fitusiran will include a larger population on the new 50 mg every other month dose regimen.”