Confirmed long-term safety and efficacy of prophylactic treatment with BAY 94-9027 in severe haemophilia A: final results of the PROTECT VIII extension study.

INTRODUCTION: The phase 2/3 PROTECT VIII main study demonstrated efficacy and safety of BAY 94-9027 (damoctocog alfa pegol; Jivi® ), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to extend its half-life. AIM: To report the final efficacy and safety data for BAY 94-9027 from the PROTECT VIII extension. METHODS: Previously treated males aged 12-65 years with severe haemophilia A (FVIII <1%) who completed the multicentre, open-label PROTECT VIII main study were eligible for the extension. Patients received either on demand or prophylaxis treatments (30-40 IU/kg twice weekly [2 × W], 45-60 IU/kg every 5 days [E5D], or 60 IU/kg every 7 days [E7D]) and could switch to any prophylaxis regimen (variable frequency) as needed. Annualised bleeding rates (ABR), zero bleeds and safety outcomes were included in this final analysis. RESULTS: At extension completion, patients (n = 121) received BAY 94-9027 for a median (range) total time of 3.9 (0.8-7.0) years. Median (Q1; Q3) total ABR was 1.49 (0.36; 4.80) for prophylaxis patients (n = 107), compared with 34.09 (20.3; 36.6) for on-demand patients (n = 14). Median total ABRs for 2 × W (n = 23), E5D (n = 33), E7D (n = 23) and variable frequency (n = 28) groups were 1.57, 1.17, 0.65 and 3.10, respectively. Of prophylaxis patients, 20.6% were bleed-free during the entire extension (median time, 3.2 years) and 50.0% were bleed-free during the last 6 months. No patient developed FVIII inhibitors. No deaths or thrombotic events were reported. CONCLUSIONS: Efficacy and safety of BAY 94-9027 was confirmed, with extension data supporting its use as a long-term treatment option for patients with haemophilia A.

Comparing Physician and Patient Perspectives on Prophylactic Treatment with BAY 94-9027 for Severe Haemophilia A: A Post Hoc Analysis.

INTRODUCTION: BAY 94-9027 is a newly developed extended half-life product to treat haemophilia, allowing for fewer injections than with standard products. This post hoc analysis aimed to compare physicians' and patients' opinions on BAY 94-9027 prophylaxis, and explore how qualitative interview data is aligned with the data from the Haemophilia-specific Quality of Life questionnaire for Adults (Haemo-QoL-A). METHODS: Exploratory qualitative interviews were conducted with physicians and patients by phone upon the exit of patients from the PROTECT VIII extension phase following a semi-directed guide. In this post hoc analysis, all transcripts were reviewed and reported concepts were compared to assess the level of concordance between physicians and patients. These qualitative data were compared with the Haemo-QoL-A mean global and subscale scores at baseline and end of main phase (36 weeks later). RESULTS: Ten physicians and 16 patients (mean age 47 years) from Israel, the Netherlands and the USA were interviewed. Significant improvements were reported by all physicians from baseline [e.g. lower frequency of bleeds (80%), improvement in emotional functioning (90%)], which is in concordance with patients' reports. The improved confidence reported by physicians cascaded to greater participation in various activities, resulting in a better perceived emotional state and a significant improvement on the Haemo-QoL-A emotional impact subscale score (p = 0.04) between baseline and end of main phase. Most physicians (80%) reported improvement in bleed frequency, as patients did (88%). Improvement in physical functioning or mobility was not consistently reported in this 8-month study. CONCLUSION: Interviewed physicians and patients generally agreed on the beneficial impact of BAY 94-9027, specifically regarding the increased level of self-confidence in patients and its subsequent positive impact on patients' lives. These findings supported the observed improvement on the Haemo-QoL-A emotional impact subscale. Overall, this study highlights the concordance between physician and patient perspective on the positive experience with BAY 94-9027.

BAY 81-8973 demonstrated efficacy, safety and joint status improvement in patients with severe haemophilia A in the LEOPOLD I extension for ≤2 years.

OBJECTIVES: BAY 81-8973 (Kovaltry® ), a full-length, unmodified, recombinant human factor VIII, provided excellent bleeding control for patients with haemophilia A in the pivotal 1-year LEOPOLD I trial. The LEOPOLD I extension evaluated long-term efficacy and safety of BAY 81-8973 prophylaxis. METHODS: After completing LEOPOLD I, patients continued receiving 20-50 IU/kg BAY 81-8973 two- or three-times weekly in the extension. Outcomes included annualised bleeding rate (ABR) and haemostasis during surgery. RESULTS: Fifty-five patients aged 12-65 years participated in the extension. Median (range) exposure days during the 2-year total study period was 309 (115-355). No patient switched regimens. Median (Q1; Q3) ABR for all bleeds was 2.0 (1.0; 6.1) during the pivotal study, 2.0 (0.0; 5.2) during the extension, and 2.0 (0.5; 5.5) combined. The proportion of joint bleeds affecting target joints decreased (pivotal study: 90.9%, extension: 60.0%). Haemostasis was assessed as excellent/good in all five major surgeries. One serious adverse event (myocardial infarction) occurred in a patient with cardiovascular risk factors. No patients developed inhibitors. CONCLUSIONS: BAY 81-8973 prophylaxis efficacy outcomes in the pivotal study were maintained or, in the case of joint protection, improved during the extension, with a safety and tolerability profile consistent with previous experience.

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.

INTRODUCTION: 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.