Matching Adjusted Indirect Comparisons of Personalized Prophylaxis with Simoctocog Alfa Versus Efmoroctocog Alfa, Damoctocog Alfa Pegol and Rurioctocog Alfa Pegol in Patients with Hemophilia a

Introduction: Prophylactic factor VIII (FVIII) therapy is the gold standard to prevent bleeding in patients with severe hemophilia A and should be individualized to patient needs. Although several FVIII products are available, the lack of head-to-head studies makes it difficult to compare their efficacy. The objective of this analysis was to indirectly compare the efficacy of personalized prophylaxis with simoctocog alfa (Nuwiq®) with three comparator FVIII products - efmoroctocog alfa (Eloctate®), damoctocog alfa pegol (Jivi®) and rurioctocog alfa pegol (Adynovate®) - among adults with severe hemophilia A.

Methods: Matching adjusted indirect comparison (MAIC) methodology was used to estimate relative treatment effects during personalized prophylaxis after matching study populations with respect to clinically important baseline characteristics. Individual patient data (IPD) from 65 patients on personalized prophylaxis with simoctocog alfa in the NuPreviq study were compared with aggregated data for efmoroctocog alfa from 117 patients in the personalized prophylaxis arm of the A-LONG study, 110 patients treated with damoctocog alfa pegol in the PROTECT VIII study, and patients treated with rurioctocog alfa pegol in the FVIII target trough level 1-3% arm (57 patients) or the 8-12% arm (58 patients) from the PROPEL study.

Following feasibility assessments for all proposed analyses, outcomes and matching variables were determined. Patients in the NuPreviq study who would have not met the inclusion criteria for the comparator studies were excluded from the analyses. Baseline age and body weight were used to re-weight the simoctocog alfa IPD such that the weighted summary statistics for simoctocog alfa matched those reported for efmoroctocog alfa; baseline age and body mass index were used for the comparison with damoctocog alfa pegol; and baseline age for the comparison with rurioctocog alfa pegol. Unanchored indirect treatment comparisons were then performed for each outcome using the weighted data for simoctocog alfa.

Results: One patient from the NuPreviq study was excluded from the comparison with damoctocog alfa pegol based on baseline age, and 10 patients from the comparison with rurioctocog alfa pegol based on body weight. After matching the populations based on baseline characteristics, the effective sample sizes (ESS) for simoctocog alfa were 44, 40, 27, and 40 for the MAIC analyses with efmoroctocog alfa, damoctocog alfa pegol, and rurioctocog alfa pegol 1-3% and 8-12%, respectively (Table 1). The percentage of patients with zero bleeds was significantly higher with simoctocog alfa for three of the analyses (Figure 1, Table 1): simoctocog alfa (75%) vs efmoroctocog alfa (45%); simoctocog alfa (76.8%) vs damoctocog alfa pegol (38.2%); and simoctocog alfa (78.4%) vs rurioctocog alfa pegol 1-3% (42.1%). The percentage of patients with zero spontaneous bleeds was significantly higher for simoctocog alfa vs rurioctocog alfa pegol 1-3%; these data were not available for efmoroctocog alfa or damoctocog alfa pegol.

The total annualized bleeding rates (ABRs) were generally lower with simoctocog alfa vs the comparators, but the difference only reached statistical significance vs damoctocog alfa pegol (Table 1). Spontaneous and joint ABRs were lower with simoctocog alfa vs rurioctocog alfa pegol 1-3%, but the differences were not statistically significant; these data were not available for efmoroctocog alfa or damoctocog alfa pegol.

The mean weekly dose was significantly higher in patients treated with simoctocog alfa compared with comparator products: simoctocog alfa vs efmoroctocog alfa (101 vs 85 IU/kg), vs damoctocog alfa pegol (97 vs 70 IU/kg) and vs rurioctocog alfa pegol 1-3% (99 vs 74 IU/kg) (Table 1). Patients treated with simoctocog alfa required a significantly lower average weekly dose than those treated with rurioctocog alfa pegol 8-12% (99 vs 143 IU/kg). Dosing of all products was consistent with the respective prescribing information.

Conclusions: The results of these indirect treatment comparisons indicate that pharmacokinetics-adjusted, individualized treatment with simoctocog alfa can lead to decreased ABRs and significantly increased zero bleed rates compared with extended half-life concentrates, albeit at a higher weekly dose.

Tiede:Octapharma: Consultancy, Honoraria, Research Funding.