Background The safety of recombinant coagulation factor IX (FIX) nonacog alfa (BeneFIX; Pfizer) has been shown in studies across a range of patient (pt) populations. This pooled analysis aimed to evaluate the safety of nonacog alfa from a 16-y database of 6 key clinical studies in pts with hemophilia B. Methods This retrospective post hoc analysis pooled data from 6 prospective, clinical, non-interventional (n=1) and interventional (n=5) studies that utilized on-demand, prophylactic, and preventive (surgical procedure) nonacog alfa regimens in previously treated, minimally treated, and untreated pts. This analysis comprised data from an open-label nonrandomized study evaluating efficacy and safety in pts with moderately severe or severe hemophilia B (Study 300); an open-label nonrandomized study evaluating efficacy and safety in children<6y with severe hemophilia B (Study 301); an open-label nonrandomized study evaluating efficacy and safety in pts ≥12y with moderately severe or severe hemophilia B (Study 302); a double-blind, randomized, crossover pharmacokinetic study followed by a 6–12-mo open-label, on-demand treatment extension in pts ≥12y with moderately severe or severe hemophilia B (Study 304); a randomized, open-label crossover study evaluating efficacy and safety in pts 6-65y with moderately severe or severe hemophilia B (Study 400); and an open-label safety registry (Study 101038). Nonacog alfa doses were determined by investigators except for the randomized, open-label crossover study, wherein pts received 2 prophylaxis regimens (50 IU/kg biweekly and 100 IU/kg once weekly). Pt demographics and clinical characteristics, nonacog alfa consumption, and safety data, including adverse events (AEs) and events of special interest, were collected and pooled. Results In total, 412 pts received treatment with nonacog alfa. Median age was 21y (range, 0-79y; 3 pts were aged 0-27d, 47 pts were 28d to<1y); 96.1% were male; 75.7% were white; and 66.5% (273/412) were previously treated pts. Pts may have received on-demand, prophylaxis, and preventive (surgical procedure) treatment in the same study. Pts received a mean (SD) dose per infusion of 64.9 (42.8) IU/kg of nonacog alfa, with 29.2 (46.3) infusions and 28.2 (44.5) exposure days per pt. In total, 220 pts (53.4%) reported AEs; the most common (≥3%) are summarized in the Table. Treatment-related AEs were reported in 48 (11.7%) pts; the most common (≥1%) included hypersensitivity (n=6; 1.5%), urticaria (n=6;1.5%), FIX inhibition (n=5; 1.2%), and pyrexia (n=4; 1.0%). Serious AEs were reported in 74 (18.0%) pts; the most common (≥1%) included hemarthrosis (n=6; 1.5%), pyrexia (n=6; 1.5%), FIX inhibition (n=5, 1.2%), device-related infection (n=4; 1.0%), hematoma (n=4; 1.0%), and arthropathy (n=4; 1.0%). Thirty-seven events of special interest occurred in 31 (7.5%) pts: 15 pts experienced allergic-type manifestations, 5 had inhibitor development , 8 reported lack of effect, 7 reported red blood cell agglutination in the tubing or syringe, and 2 experienced thrombogenicity. Seven pts (1.7%) were withdrawn from the studies due to AEs of hypersensitivity (n=3), drug eruption, rash pruritic, urticaria, and therapeutic response decreased (n=1 each). Conclusions In this pooled safety analysis of pts with hemophilia B that represents a total of 11,588 exposure days, nonacog alfa was generally well tolerated, with a low rate of inhibitor development and allergic-type manifestations. The safety profile was consistent with previous studies. No new or unexpected safety signals were observed across various pt populations, including minimally treated, previously treated, and untreated pts, adults as well as children<18y, pts with mild, moderate, or severe hemophilia B, and pts receiving on-demand , prophylactic, and preventive treatment. Disclosures: Rendo: Pfizer Inc.: Employment. Smith:Pfizer Inc.: Employment. Hsiao-Yu:Pfizer Inc.: Employment. Shafer:Pfizer Inc.: Employment.

Nonacog alfa is a recombinant factor IX (FIX) product indicated for treatment and prevention of bleeding episodes in patients with haemophilia B. This posthoc analysis evaluated the safety of nonacog alfa in key clinical studies across 15 years. Data were pooled from six prospective studies that utilized on-demand, prophylactic and preventive nonacog alfa regimens: three open-label, nonrandomized studies that assessed efficacy and safety; a bioequivalence study of original and reformulated nonacog alfa; an open-label, randomized study that compared on-demand and prophylactic treatment; and a noninterventional observational registry study that evaluated safety. Safety assessments included adverse events, serious adverse events (SAEs) and events of special interest. In total, 412 patients received nonacog alfa treatment. Adverse events occurred in 220 patients (53.4%), the most common being pyrexia (n = 63), nasopharyngitis (n = 53) and cough (n = 52). Forty-eight patients (11.7%) experienced treatment-related adverse events; the most common were hypersensitivity (n = 6), urticaria (n = 6), FIX inhibition (n = 5) and pyrexia (n = 4). Seventy-four patients (18.0%) developed SAEs. Thirty-seven events of special interest occurred in 31 (7.5%) patients. Events of special interest included allergic-type manifestations (n = 15), inhibitor development (n = 5), lack of effect (n = 8), red blood cell agglutination in tubing or syringe (n = 7), and thrombogenicity (n = 2). Six patients (1.5%) withdrew due to seven adverse events: hypersensitivity (n = 3), drug eruption, pruritic rash, urticaria and decreased therapeutic response (n = 1 each). Four patients died during the study; no deaths were related to study medication. This pooled safety analysis in haemophilia B patients confirmed the safety of nonacog alfa across various patient populations.