Results of the BASIS trial demonstrate the efficacy and safety of once-weekly SC marstacimab prophylaxis up to 12 months in male adolescents and adults with severe haemophilia A* (HA) or severe-to-moderately-severe haemophilia B** (HB) with no detectable or documented history of inhibitors against factors VIII or IX, and who were receiving on-demand (OD) or routine prophylaxis (RP) prior to enrolment.
A total of 128 participants (median age 30 years, 47.7 percent Asian) entered the 6-month observational phase and continued their prescribed therapy (n=37 and 91 for OD and RP, respectively). Most participants were adults (84.4 percent) and had HA (78.9 percent). The 12-month active treatment phase (ATP) ensued thereafter, wherein 116 participants (n=33 and 83 for OD and RP, respectively) received a single loading dose of SC marstacimab 300 mg, followed by once-weekly marstacimab 150 mg.
Adherence rates were 97 percent and 98.8 percent in the respective OD and RP groups. [Blood 2025;146:1654-1663]
In the ATP, there was a 92-percent reduction in the mean annualized bleeding rate (ABR) of treated bleeds with marstacimab than with prior OD therapy (3.2 vs 39.86; estimated ABR ratio, 0.080; p<0.0001), demonstrating the superiority of the former over the latter.
A similar effect favouring marstacimab over RP was observed (mean ABR, 5.09 vs 7.9 [35.5-percent reduction]; p=0.0349), demonstrating the noninferiority and superiority of marstacimab relative to RP.
For the key secondary*** bleeding endpoints, marstacimab was consistently superior to OD therapy (p<0.0001 for all) and noninferior to RP.
Safety during ATP
There were no deaths or thromboembolic (TE) events. Seventy-four participants experienced adverse events (AEs), the most common being COVID-19–related events and headache. Most AEs were mild to moderate in severity.
In the OD group, one case of grade 1/2 thrombosed haemorrhoids was successfully managed with incisional drainage without treatment disruption.
In the RP group, seven participants experienced ≥1 serious AE. One event (grade 1 peripheral swelling) was deemed treatment-related. One event (meningioma) was not treatment-related, but the patient discontinued the study for the potential risk of thrombosis post-surgical resection and radiotherapy.
Eleven participants (n=2 and 9 in the OD and RP groups, respectively) reported injection-site reactions (ISRs), but these were mild and transient. “[The ISRs] were relatively infrequent and did not lead to discontinuation, suggesting that the tolerability of SC delivery may have contributed to high adherence,” the researchers said.
Unmet need remains
Some of the challenges associated with haemophilia treatment include low adherence to IV injections, inhibitory antibodies, venous access difficulties, and inconsistent haemostatic protection. These have led to the development of non-factor treatment alternatives that require less frequent SC administration. [Haemophilia 2021;27:340-350; Lancet 2021;397:630-640; Blood 2019;133:399-406]
Emicizumab was the first non-factor agent approved for prophylactic treatment of HA, but not HB, given the associated TE events. [Haemophilia 2020;26:1-158; J Thromb Haemost 2023;21:546-552] TE events with other non-factor agents, including anti-tissue factor pathway inhibitor antibodies, concizumab, and befovacimab, have also been reported. [N Engl J Med 2023;389:783-794; Haemophilia 2022;28:702-712]
“As such, an unmet need for alternative therapies for haemophilia with an improved benefit-risk profile remains,” the researchers said.
In this phase III study, marstacimab prophylaxis was associated with reductions in ABR, dosing frequency, and factor replacement consumption, with a high overall adherence rate; it was also safe and well-tolerated. The ongoing open-label extension will ascertain the long-term efficacy and safety of marstacimab, the investigators said.
“Extended follow-up and real-world evidence of non-factor therapies will determine whether AEs are time-dependent and whether non-haemostatic side effects may arise as a consequence of treatment,” they added.