Efanesoctocog alfa shows superior bleed protection in severe hemophilia A
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Key takeaways:
- Patients who received prophylactic efanesoctocog alfa had a median annual bleed rate of 0.
- 72.2% of those who received prophylactic efanesoctocog alfa did not experience any joint bleeds during the study period.
- Patients with hemophilia A will be able “to aspire to lifestyle goals that previously were not feasible,” researcher says.
A once-weekly dose of prophylactic efanesoctocog alfa conferred a significant reduction in annualized bleed rate compared with the use of prophylactic factor VIII agents, results of the pivotal phase 3 XTEND-1 study showed.
Data from the trial, presented at International Society on Thrombosis and Haemostasis 2022 Congress, revealed that prophylactic efanesoctocog alfa (Sobi, Sanofi) offered significant improvements in physical health, pain and joint health 1 year after the start of treatment, the investigators noted.
Background
Efanesoctocog alfa is a novel fusion protein with a longer half-life than other recombinant factor VIII replacement therapies. The FDA granted the investigational treatment breakthrough therapy designation for the treatment of hemophilia A.
Patients with hemophilia A still experience joint bleeds despite standard-of-care therapy with currently available factor VIII prophylaxis products, according to Annette von Drygalski, MD, PharmD, professor of medicine and director of the Hemophilia and Thrombosis Treatment Center at UC San Diego Health.
“This approach results in hemophilic arthropathy — a very debilitating condition for aging patients with hemophilia,” she told Healio. “There is great unmet need because these factor VIII products — even if they have extended half-lives — inflict a high treatment burden on patients.”
Traditional factor VIII therapy requires patients to receive infusions up to four times per week that results in peaks and troughs in patient blood levels The goal with efanesoctocog alfa, von Drygalski added, is to reduce this treatment burden by giving a therapy less frequently that provides “an extra level of protection” because it produces even levels of factor VIII in the blood without the trough periods seen with currently available therapies.
Methodology
The multicenter XTEND-1 study included 159 patients (mean age, 35.4 ± 15.1 years) aged 12 years or older who received once-weekly efanesoctocog alfa for previously treated advanced hemophilia A.
Investigators divided the study into two arms, with one group (Arm A; n = 133; 99.2% men) comprising patients who previously received prophylactic therapy and were given prophylactic efanesoctocog alfa dosed at 50 IU/kg once weekly for 52 weeks. The other group (Arm B; n = 26; 100% men) included patients who received previous on-demand therapy and were given on-demand efanesoctocog alfa dosed at 50 IU/kg for 26 weeks followed by prophylactic efanesoctocog alfa at the same dose weekly for another 26 weeks.
Annualized bleed rate in Arm A served as the study’s primary endpoint. Secondary endpoints included intrapatient annualized bleed rate comparison, joint health outcomes, quality-of-life measurements, safety and tolerability.
Key findings
The trial met its primary endpoint by providing clinically meaningful bleeding protection for patients with severe hemophilia A.
Results showed a median annualized bleed rate of 0 (interquartile range, 0-1.04) and a model-based mean annual bleed rate of 0.71 (95% CI, 0.52-0.97) for patients in Arm A who received 52 weeks of prophylactic treatment with efanesoctocog alfa.
The trial also met its secondary endpoint by showing superior disease control for efanesoctocog alfa compared with previous factor VIII prophylaxis.
Mean plasma factor VIII activity remained at or above 40% through day 4 after weekly treatment with efanesoctocog alfa, with 12.8% noted 7 days after treatment.
The researchers noted an estimated mean annualized bleed rate reduction of 77% among patients who received prophylactic efanesoctocog alfa (P < .0001).
Nearly two-thirds of patients (64.7%) in Arm A did not experience any bleeds during the study. Additionally, 76.9% of patients in Arm B had no bleeds during study’s prophylaxis period.
Compared with baseline, patients in the efanesoctocog alfa prophylaxis arm (Arm A) reported significantly improved quality-of-life scores (P = .0001) and significantly lower pain intensity (P = .0276) by the end of the 52-week study period.
Patients in Arm A also reported significantly improved joint health (P = .0101) compared with baseline, with 72.2% not experiencing any joint bleeds during the study period.
Most patients (77.4%) experienced at least one treatment-related adverse event and 9.4% reported at least one serious event.
The most common treatment-related adverse events included headache (20.1%), arthralgia (16.4%) and fall (6.3%).
No patients developed detectable factor VIII inhibitors after study treatment.
Researchers noted one death and two patients discontinuing treatment due to treatment-related adverse events.
Clinical implications
Efanesoctocog alfa represents a new class of factor VIII molecule, von Drygalski said. She said its unique design allows it to escape the usual von Willebrand factor-imposed half-life ceiling that limits all other factor VIII preparations on the market today.
“[This] is the first single weekly infusion that has shown the ability to maintain stable factor VIII levels that fall within the normal to near-normal range,” she told Healio.
"I think that efanesoctocog alfa will revolutionize factor VIII prophylaxis,” she added. “It will allow patients with hemophilia to aspire to lifestyle goals that previously were not feasible.”
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von Drygalski A, et al. Abstract LB 01.4. Presented at: International Society on Thrombosis and Haemostasis 2022 Congress; July 9-13, 2022; London.
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