Simoctocog Alfa Effective, Safe in Children With Severe Hemophilia A

Data from recent studies published in Therapeutic Advances in Hematology show that simoctocog alfa both prevents and treats bleeding in children with severe hemophilia A, with low rates of inhibitor development.¹

Findings from 2 prospective, open-label, noncontrolled clinical trials demonstrate reduced bleeding rates and low rates of inhibitor development with simoctocog alpha. The NuProtect trial, which enrolled 108 patients (median age, 12 months) with severe hemophilia A who were previously untreated (PUPs), focused on the immunogenicity of simoctocog alpha.² Inhibitor development was evaluated in 105 PUPs treated for a median of 100 exposure days (EDs). Inhibitors developed in 28 children (26.7%) after a median of 11 EDs. Of those, high-titer inhibitors (≥ 5 BU/mL) were observed in 17 children (16.2%) and low-titer inhibitors (0.6 to < 5 BU/mL) were observed in 11 children (10.5%). There was no inhibitor development in patients with non-null F8 mutations.

The suthors of this investigation stress the ongoing importance of real-world studies for insight on simoctocog alfa use in children | Image Credit: Rawpixel.com-stock.adobe.com

A separate case series involving 10 children evaluated the effectiveness of immune tolerance induction (ITI), which was defined as the achievement of at least 2 of 3 internationally recognized criteria: inhibitor titer below 0.6BU/mL, normalization of factor VIII (FVIII) recovery (> 66% of normal), and normalization of FVIII half-life (> 6 h). Negative inhibitor titers were achieved in 8 children (80%) within a median 3.5 months. All 8 children achieved ITI success in a median of 7.5 months.

The GENA-03 study focused on annualized bleeding rates (ABRs) and enrolled 59 previously treated patients (PTPs) aged 2 to 12 years.³ The study reported median ABRs of 0 for spontaneous bleeds, 0 for joint bleeds, and 1.9 for all bleeds. Long-term efficacy was further demonstrated in the GENA-13 extension study, involving 49 patients with a median follow-up of 30 months. The ABRs in this extension study were 0.3 for spontaneous bleeds, 0.4 for joint bleeds, and 1.7 for all bleeds.

A pooled analysis of long-term efficacy data from the NuProtect-Extension study (GENA-05/15) and GENA-13 included 96 children who received simoctocog alfa for a median of 359 EDs for up to 5 years (median duration, 36.4 months) from the time of the patient’s first prophylactic dose in the main study to the completion of the extension study. The median ABRs for spontaneous and total bleeds were 0.3 and 1.8, respectively, with median spontaneous and total joint ABRs of 0 and 0.4, respectively. Additionally, 43 children (45%) experienced no spontaneous breakthrough bleeds during the follow-up period. The authors report that bleeding rates during long-term prophylaxis with simoctocog alfa are consistent with those reported from long-term extension studies investigating the efficacy of other recombinant FVIII products.⁴

Of the 96 children in the extension study who received long-term simoctocog alfa prophylaxis, 86 children experienced 851 breakthrough bleeds, 500 (58.8%) of which were considered major. Simoctocog alfa was used to treat 763 breakthrough bleeds, with 85.1% of bleeds treated successfully.

There were no treatment-related deaths or thromboembolic events reported among the 167 children who participated in the clinical trials. The safety profile was consistent with previous reports, with adverse events including pyrexia, hypersensitivity, back pain, headache, dyspnea, anemia, and hemorrhagic anemia.

Clinical trials were all prospective, international, open-label, noncontrolled studies. All children in GENA-03, GENA-13, and the NuProtect-Extension study received prophylaxis, whereas children in NuProtect received prophylaxis or on-demand treatment at the treating physician's discretion.

Ongoing real-world and scientific studies will continue to provide valuable insights into the long-term management and outcomes of children treated with simoctocog alfa. These studies are important because, as the authors reiterate, “Effective prophylaxis offers children the opportunity to participate in regular daily activities and live a healthy life."

References

1. Klukowska A, Sidonio RF Jr, Young G, et al. Simoctocog alfa (Nuwiq) in children: early steps in life’s journey for people with severe hemophilia A. Ther Adv Hematol. 2024;15:1-13. doi:10.1177/20406207241245511

2. Liesner RJ, Abraham A, Altisent C, et al. Simoctocog alfa (Nuwiq) in previously untreated patients with severe haemophilia A: final results of the NuProtect study. Thromb Haemost. 2021;121(11):1400-1408. doi:10.1055/s-0040-1722623

3. Klukowska A, Szczepański T, Vdovin V, Knaub S, Jansen M, Liesner R. Novel, human cell line-derived recombinant factor VIII (Human-cl rhFVIII, Nuwiq) in children with severe haemophilia A: efficacy, safety and pharmacokinetics. Haemophilia. 2016;22(2):232-239. doi:10.1111/hae.12797

4. Klukowska A, Szczepański T, Vdovin V, et al. Long-term tolerability, immunogenicity and efficacy of Nuwiq (human-cl rhFVIII) in children with severe haemophilia A. Haemophilia. 2018;24(4):595-603. doi:10.1111/hae.13460