NUWIQ® – Safety in Previously Untreated Patients (PUPs)

Inhibitor Risk in Previously Untreated Patients (PUPs)

Type of FVIII Molecule Can Affect Inhibitor Risk in PUPs

In the SIPPET Study, rFVIII Products from Hamster Cells (CHO or BHK) Had a Higher Incidence of Inhibitor Development than pdFVIII Products1

  • The SIPPET study compared the rates of inhibitor development in PUPs who were treated with either plasma-derived FVIII (pdFVIII) or recombinant FVIII (rFVIII) made from hamster cells
  • Results from the SIPPET study showed:
    • PUPs treated with rFVIII from hamster cells had a 28.4% incidence of high-titer inhibitors
    • PUPs treated with pdFVIII had a 18.6% incidence of high-titer inhibitors

SIPPET: Cumulative Incidence of High-Titer Inhibitors (N=251)

The SIPPET Study compared the incidence of inhibitors in PUPs with severe Hemophilia A treated with either pdFVIII or rFVIII derived from hamster cells (Chinese Hamster Ovary [CHO] cells or Baby Hamster Kidney [BHK] cells). Patients were followed for 50 consecutive exposure days (EDs), or 3 years, or until inhibitor development was confirmed.

Differences in incidence of high-titer inhibitor rates between pdFVIII and rFVIII were not found to be statistically significant. SIPPET authors suggested this may have been due to the small sample size of the study.
SIPPET = Survey of Inhibitors in Plasma-Product Exposed Toddlers; CI = confidence interval.

NuProtect Logo Final Results Confirm Low Rate of Inhibitors with NUWIQ in PUPs2,3§

  • NuProtect is the largest prospective study with a single FVIII product
  • In the final analysis, data from 105 PUPs treated with NUWIQ were analyzed for inhibitor development. Ninety-six patients reached completion of the study, either by receiving NUWIQ for 100 EDs without developing an inhibitor (including 5 patients with 97–99 EDs due to miscounting), or by developing an inhibitor.

Final NuProtect results demonstrated a 16.2% absolute incidence of high-titer inhibitors with NUWIQ in PUPs—and a cumulative incidence of high-titer inhibitors of 17.6%.2,3

NuProtect: Cumulative Incidence of High-Titer Inhibitors (N-105)§

In the NuProtect Study, cumulative incidence of high-titer inhibitors for NUWIQ was 17.6%; similar to pdFVIII and lower than hamster-derived rFVIII inhibitor incidence observed in the separate SIPPET study.§

§ Information from the NuProtect study is presented in parallel to the SIPPET study for context, but please note that these trials were performed under different conditions and with different populations. The observed incidence of inhibitor formation may be influenced by a number of factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

Ellis Neufeld, MD, Presents the Final Results of the NuProtect Study

NuProtect: No Inhibitors Were Reported in PUPs with Non-null F8 Mutations

Incidence of inhibitor development by F8 mutation status (Null vs Non-Null)

SIPPET Study NuProtect Study
Null F8 Mutations
N = 197
Non-Null F8 Mutations
N = 38
Null F8 Mutations
N = 90
Non-Null F8 Mutations
N = 12
pdFVIII/VWF
(N = 101)
rFVIII hamster
cell line (N = 96)
pdFVIII/VWF
(N = 16)
rFVIII hamster
cell line (N = 22)
Null F8 Mutations
N = 90
NUWIQ
Non-Null F8 Mutations
N = 12
NUWIQ
All Inhibitors 31% 47% Zero 43% 30% ZERO
High-Titer Inhibitors 22% 30% Zero 24% 18.9% ZERO
  • Among SIPPET patients with null F8 mutations, cumulative incidence of inhibitors was 31% with pdFVIII and 47% with rFVIII. Among SIPPET patients with non-null F8 mutations, no inhibitors developed with pdFVIII treatment, whereas 43% developed inhibitors with rFVIII.
  • No inhibitors were reported in PUPs with non-null F8 mutations treated with NUWIQ or pdFVIII.
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References
  1. Peyvandi F, et al. N Engl J Med. 2016;374:2054-2064.
  2. NUWIQ full Prescribing Information. Paramus, NJ: Octapharma; rev 2020.
  3. Liesner, R. J., et al. Alfa (Nuwiq) in Previously Untreated Patients with Severe Haemophilia A: Final Results of the NuProtect Study. Thrombosis and haemostasis. 2021; Advance online publication. https://doi.org/10.1055/s-0040-1722623.