Safety and efficacy of BAY 94-9027, an extended-half-life factor VIII, during surgery in patients with severe hemophilia A: Results of the PROTECT VIII clinical trial

Abstract

Ensuring hemostasis during invasive procedures is a challenge in patients with severe hemophilia A. This analysis evaluated efficacy and safety of BAY 94-9027, an extended-half-life recombinant factor VIII (FVIII), in the surgical setting. Materials and methods: Patients participating in an open-label BAY 94-9027 clinical trial who underwent major surgery were included in the analysis. Investigator/surgeon assessment of hemostasis during surgery was the primary outcome. In addition, information about FVIII use, FVIII levels during perioperative period, bleeding complications and FVIII inhibitor development were collected. Results: Data were analyzed for 26 major surgeries (orthopedic, n = 21) in 20 patients aged 13-61 years. BAY 94-9027 provided effective hemostasis during all procedures. FVIII levels 6-8 h post preoperative infusion and prior to the first follow-up infusion were in the range expected to maintain protection in the major surgery setting. The median time from preoperative infusion to the first follow-up infusion (the first infusion administered after the preoperative infusion) was 12.33 (3.6-49.9) h. No intraoperative bleeding complications occurred, and no new inhibitors developed following any surgery. Conclusions: The results of the study demonstrate that BAY 94-9027 was efficacious and well tolerated in the treatment of patients undergoing major surgeries. Advantages of BAY 94-9027 include the potential for less frequent infusion and reduced factor consumption, which should simplify the management of patients during major surgery.

Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials

“…In pathfinder 3, postoperative bleeds were reported in 8.2% (n = 4/49) of procedures. In other studies, postoperative bleeds were reported with rFVIIIFc in 4.3% (n = 1/23), 12 with BAX 855 in 23.8% (n = 5/21) 11 and with BAY 94‐9027 in 7.7% (n = 2/26) 18 of major/minor surgeries, respectively. A variety of major orthopaedic/non‐orthopaedic procedures were successfully performed with turoctocog alfa pegol.…”

“…Twenty‐one major and five minor procedures were reported with BAX 855 treatment, with haemostasis successful in all procedures 11 . Similarly, haemostasis was rated effective for all 26 major surgeries undertaken in adults/adolescents using BAY 94‐9027 18 …”

“…Surgery increases the risk of inhibitor development in patients with haemophilia due to the intensive nature of treatment 26 ; however, no inhibitor development or thromboembolic events were reported. Other EHL products (BAX 855, rFVIIIFc and BAY 94‐9027) were also shown to be well tolerated in the perioperative setting with no inhibitor development, 11‐12,18 suggesting that EHL products seem to have a low immunogenicity potential when used during surgery in previously treated patients 27 …”

Direct comparison of two extended half-life PEGylated recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A

“…A second distribution compartment could not be identified for damoctocog alfa pegol (CV on Q = 103%); the PK of damoctocog alfa pegol was adequately described by a onecompartment model (technically, the PK of damoctocog alfa pegol was described by a two-compartment model fixing Q to a very small value [0.001]), while a two-compartment model was used for rurioctocog alfa pegol. Compared with damoctocog alfa pegol, the CL of rurioctocog alfa pegol was significantly increased by 21% (95% CI, [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. This effect was consistent across patients with an estimated betweenpatient variability of 11.5% CV and 17 out of 18 patients having a CL value in favor of damoctocog alfa pegol compared with rurioctocog alfa pegol, respectively.…”

“…Rurioctocog alfa pegol is a full-length rFVIII product that has been PEGylated at its B-domain, with a branched 20-kDa PEG molecule (Advate®; Baxter, USA) [12,13]. Rurioctocog alfa pegol was first licensed in 2015, and damoctocog alfa pegol in 2018, for the treatment of hemophilia A, based on efficacy and safety data from their respective pivotal phase 2/3 clinical trials [14][15][16][17][18][19].…”