Immunogenicity of Two Plasma-Derived FVIII Products and Simoctocog Alfa in Previously Untreated Patients According to F8 Mutation Type

Abstract

Background: The SIPPET study investigated inhibitor development in 251 previously untreated patients (PUPs) treated with either plasma-derived FVIII products containing von Willebrand factor (pdFVIII/VWF; n = 125), or recombinant FVIII (rFVIII; n = 126) from hamster cell lines. Amongst PUPs with non-null F8 mutations, none developed inhibitors when treated with pdFVIII/VWF while the cumulative inhibitor incidence was 43% in those treated with hamster-cell-derived rFVIII. In patients with null F8 mutations, the cumulative inhibitor incidences were 31% and 47% in patients treated with pdFVIII/VWF and rFVIII, respectively. In patients with null mutations the cumulative incidences of high-titre inhibitors were 22% and 30% with pdFVIII/VWF and rFVIII, respectively. Aim: To investigate the relationship between inhibitor development and F8 mutation type in PUPs with severe hemophilia A treated with either a rFVIII from a human cell line (Nuwiq®; simoctocog alfa) or either of two pdFVIII/VWF products, one with a VWF/FVIII ratio of 0.4 (octanate®) the other with a VWF/FVIII ratio of 1.0 (wilate®). Materials and Methods: Data from completed multicenter, prospective trials with octanate® and wilate® and interim data from the NuProtect study with Nuwiq® were analyzed. Data on F8 mutation type were available for 50/51, 27/28 and 58/66 patients in each of the studies. All patients in the three studies had no previous treatment with FVIII concentrates or other blood products containing FVIII. Results: In the three studies, 18% (9/50), 7.4% (2/27) and 19%.0% (11/58) of patients had non-null mutations. None of the patients with non-null mutations developed inhibitors with octanate®, wilate® or Nuwiq®. In patients with null mutations, 9.8% (4/41), 12.0% (3/25), and 17.0% (8/47) developed high-titre inhibitors. Conclusions: PUPs with non-null F8 mutations did not develop inhibitors when treated with octanate®, wilate® or Nuwiq®. Whilst the different studies are not directly comparable, the findings with these products, two pdFVIII/VWF and a rFVIII from a human cell line, show similar behavior to the SIPPET trial where no patients with non-null mutations treated with pdFVIII/VWF products developed inhibitors. Disclosures Liesner: Bayer: Consultancy, Research Funding; Baxalta: Consultancy, Research Funding; Novo Nordisk: Research Funding, Speakers Bureau; Roche: Research Funding; Sobi: Speakers Bureau; Octapharma: Consultancy, Other: Clinical study investigator for NuProtect Study (Octapharma sponsored), Research Funding, Speakers Bureau. Versteden:Octapharma AG: Employment. Lowndes:Octapharma AG: Employment. Belyanskaya:Octapharma AG: Employment. Oldenburg:Grifols: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding; Biotest: Honoraria, Research Funding; Biogen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; Shire: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Swedish Orphan Biovitrum: Honoraria, Research Funding. Pavlova:Novo Nordisk: Honoraria; Octapharma: Honoraria.

Design of a Real-World Observational Study in Previously Untreated and Minimally Treated Hemophilia A Patients: Protect-NOW

“… 14 20 No PUPs with a nonnull F8 gene mutation developed an inhibitor in clinical trials with Nuwiq, octanate, or wilate. 14 20 26 These data suggest that Nuwiq, which is produced in a human cell line, has an immunogenicity profile more similar to pdFVIII than to rFVIII products produced in hamster cell lines.…”