Interim Subgroup Analysis of the Effectiveness and Safety of Damoctocog Alfa Pegol Prophylaxis in Previously Treated Patients with Hemophilia A Treated Every 5 or Every 7 Days: Results from the Real-World Observational HEM-POWR Study

Background: Extended half-life (EHL) FVIII products have been developed to reduce the burden of frequent intravenous infusions for people with hemophilia A (HA). Damoctocog alfa pegol is an EHL PEGylated B-domain-deleted recombinant FVIII concentrate approved for use in previously treated patients (PTPs) aged ≥12 years with HA. The recommended initial prophylactic dosing regimen in the USA is twice weekly, which may be adjusted to every 5 days (E5D) and can then be individually tailored to less or more frequent dosing based on bleeding episodes (FDA 2018). The safety and efficacy of extended dosing intervals were demonstrated in the pivotal PROTECT VIII studies (Reding et al, Haemophilia 2021). Real-world safety and effectiveness of damoctocog alfa pegol administered with any dosing regimen has been reported in the previously presented interim analyses of the HEM-POWR study (Reding et al., ISTH 2021, 2022). However, separate analyses of E5D or every-7-day (E7D) prophylaxis regimens in the real-world have not yet been reported.

Objective: Post hoc analysis to explore the safety and effectiveness of extended dosing with damoctocog alfa pegol in PTPs receiving prophylactic treatment in the ongoing real-world HEM-POWR study.

Methods: HEM-POWR (NCT03932201) is a prospective, multinational, observational open-label Phase IV cohort study of damoctocog alfa pegol in PTPs with mild, moderate, and severe HA. Patients in this subgroup analysis received prophylactic damoctocog alfa pegol E5D or E7D. The primary endpoint was annualized bleeding rate (ABR), and secondary endpoints included measures of joint health and safety. Safety analyses were primarily performed on treatment-emergent adverse events (TEAEs) in the safety analysis set population. Effectiveness analyses were primarily performed on the full analysis set (FAS). Data were captured from patient diaries and physician records, and ethical approval was obtained for all sites.

Results: At data cut-off (31 August 2021), a total of 162 patients were enrolled in the study. In this subgroup analysis, 21 patients in the FAS received prophylactic treatment E5D (n=14) or E7D (n=7). The majority of patients had severe HA (n=12/14, 85.7% E5D; n=5/7, 71.4% E7D). Prior to initial visit, all patients received FVIII replacement therapy; some of these patients received prior damoctocog alfa pegol prophylactic treatment (n=7/14, 50.0% E5D; n=5/7, 71.4% E7D).

The proportion of patients with no affected joints increased over time in both E5D and E7D subgroups (Figure 1). In the E5D subgroup at follow-up 1 (n=10), 40.0% of patients had no affected joints. In the E7D subgroup, all patients reported no affected joints at the first follow-up (n=5).

Median (mean, SD) total ABR was 0.0 (1.0, 1.6) for the E5D subgroup and 0.0 (0.8, 1.5) for the E7D subgroup. The median (mean, SD) difference in ABR between observation period and prior to initiation of damoctocog alfa pegol in the E5D and E7D subgroups is reported in Table 1. No development of FVIII inhibitors, TEAEs, or deaths were reported.

Conclusions: Damoctocog alfa pegol continues to show a favorable effectiveness and safety profile in PTPs with mild, moderate, or severe hemophilia in a real-world clinical setting with extended prophylactic dosing intervals. Improvements in joint health and ABR were demonstrated with both E5D and E7D prophylaxis regimens. The option of extended dosing intervals allows for further PK-guided treatment individualization for selected patients, based on bleeding phenotype and lifestyle, without compromising treatment efficacy.

References

Bayer. Damoctocog alfa pegol (Jivi®). Prescribing Information. Last updated August 2018. Available at: https://www.fda.gov. Accessed: July 2022.

Reding MT, Pabinger I, Holme PA, et al. Haemophilia. 2021;27:e347-e356.

Reding M, Alvarez Román M, Sanabria M, et al. [abstract presented at ISTH 2021]. Res Pract Thromb Haemost. 2021;5(Suppl 2).

Reding M, Alvarez Román M, Sanabria M, et al. [abstract presented at ISTH 2022]. https://abstracts.isth.org/abstract/annualised-bleeding-rate-and-joint-health-second-interim-analysis-of-the-real-world-hem-powr-study-evaluating-the-effectiveness-of-damoctocog-alfa-pegol-in-patients-with-haemophilia-a/. Accessed July 19, 2022.

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