Revised terminal half-life of nonacog alfa as derived from extended sampling data: A real-world study involving 64 haemophilia B patients on nonacog alfa regular prophylaxis.

Abstract

Nonacog alfa, a standard half-life recombinant factor IX (FIX), is used as a prophylactic treatment in severe haemophilia B (SHB) patients. Its half-life determined in clinical studies involving a limited sampling (72h) was shown to be rather short. In our clinical practice, we suspected that its half-life could have been underestimated. We aimed to evaluate nonacog alfa pharmacokinetics in real world clinical practice based on FIX levels in patients receiving prophylaxis. We retrospectively collected data on patients with SHB receiving prophylaxis from eight centres across France. The terminal half-life (THL), time to reach 5-2IU/dl and FIX activity at 48, 72 and 96h were derived by Bayesian estimations using NONMEM analysis. Infusion data (n=455) were collected from 64 patients with SHB. The median THL measured in 92 pharmacokinetic (PK) studies was 43.4h. In 26 patients ≤12 years of age, 51 PK studies showed a median time to reach 5IU/dl of FIX of 70.5h and a median time to reach 2IU/dl of 121.5h. In 38 patients 13-75 years of age, 41 PK studies showed a median time to reach 5IU/dl of FIX of 92.0h and a median time to reach 2IU/dl of 167.5h. Extending the sampling beyond 72h makes it possible to observe a plateau, with FIX remaining between 2 and 5IU/dl for several days and shows that the THL of nonacog alfa might be longer than previously described. Nonacog alfa terminal half-life (THL) in patients receiving regular prophylaxis was evaluated in clinical practice. The median THL was estimated to be 36.9h for patients aged .8-12 years. The median THL was estimated to be 49.9h for patients aged 13-75 years. For patients aged ≤12 and>12 years, the median times to reach 5IU/dl were 70.5 and 92 h, respectively; to reach 3IU/dl, 95.5 and 131.5 h, respectively; to reach 2IU/dl, 121.5 and 167.5 h, respectively. We suggest that the half-life of nonacog alfa might be longer than previously described in both younger and older patients.