BAY 94‐9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results

Abstract

Introduction: BAY 94-9027 is an extended-half-life, site-specifically PEGylated, Bdomain-deleted recombinant factor VIII (FVIII). The PROTECT VIII main study demonstrated efficacy of bleed control using extended-interval prophylaxis with BAY 94-9027 for 36 weeks. Aim: To report long-term efficacy and safety of prophylaxis with BAY 94-9027 in a descriptive analysis of the ongoing PROTECT VIII extension with a total treatment time of up to >5 years. Methods: Previously treated males aged 12-65 years with severe haemophilia A who completed the PROTECT VIII main study were eligible for the open-label extension.Patients received on-demand treatment or prophylaxis (30-40 IU/kg twice weekly, 45-60 IU/kg every 5 days, or 60 IU/kg every 7 days) and could switch regimens as needed.Results: Patients (N = 121; on demand, n = 14; prophylaxis, n = 107) accumulated a median (range) of 3.9 years (297-1965 days) and 223 (23-563) total exposure days by 31 January 2018. During the extension, median (quartile [Q]1; Q3) annualized bleeding rates (ABRs) for total bleeds were 1.6 (0.3; 4.6) for patients receiving prophylaxis and 34.1 (20.3; 36.6) for patients receiving on-demand treatment. ABRs for twiceweekly (n = 23), every-5-days (n = 33), every-7-days (n = 23) and variable frequency (n = 28) treatments were 1.7, 1.2, 0.7 and 3.1, respectively. Of prophylaxis patients, 20.6% were bleed-free throughout the extension (median time, 3.2 years), and 51.0%were bleed-free during the last 6 months. No patients developed FVIII inhibitors.Conclusions: BAY 94-9027 prophylaxis was efficacious and well tolerated with dosing intervals up to every 7 days for a median (range) of 3.9 years (0.8-5.4 years). K E Y W O R D Sclinical trial, factor VIII, haemophilia A, intravenous infusions, recombinant proteins 1012 | LALEZARI Et AL. | INTRODUC TI ONFor patients with haemophilia A, replacement of factor VIII (FVIII) with routine prophylaxis can effectively reduce or prevent bleeds and ultimately preserve long-term joint function. 1,2 Prophylaxis initiation is recommended as early as possible for patients with severe disease (FVIII:C < 1%), 3,4 but prophylaxis initiated at later ages and following onset of joint damage may also improve patient outcomes. 5 Despite the established benefits of prophylaxis, several barriers persist, including lack of optimal adherence to a prescribed dosing regimen because of the time commitment and lifestyle adjustments needed to maintain frequent infusions. 6 This barrier may limit treatment success. 7 Individualized prophylaxis, a strategy of tailored dosing based on a patient's unique bleeding pattern and characteristics, pharmacokinetic (PK) profile, lifestyle and needs, may be a cost-effective method of mitigating disease burden by decreasing the number of intravenous injections, reducing the frequency and number of bleeds, improving long-term joint function, improving quality of life, and reducing overall FVIII consumption. 8-14 Recently developed extended-half-life products may further allow for individualization of...

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].…”

Target joint resolution in patients with haemophilia A receiving long‐term prophylaxis with BAY 94‐9027

“…Of the 126 patients who completed the main study, 121 entered the extension that confirmed the safety and efficacy of BAY 94-9027 prophylaxis with dosing intervals of up to every 7 days for >5 years 9. Given the importance of preventing joint damage for patients with severe haemophilia A, we performed a post hoc analysis on…”

Enhanced Half-Life Recombinant Factor VIII Concentrates for Hemophilia A: Insights from Pivotal and Extension Studies

“…A total of 107 subjects completed the extension study, receiving prophylaxis with BAY 94-9027 (twice weekly, n ¼ 23; 5 days, n ¼ 33; 7 days, n ¼ 23; variable frequency, n ¼ 28). 34 The overall FVIII consumption in the prophylaxis group was 290 IU/kg/month, 326 in the twice-weekly arm, 290 in the 5-day arm, and 260 in the 7-day arm. The median ABR in the overall prophylaxis group was 1.6, with 21% of subjects reporting zero bleeding episode.…”