BAY 94-9027, developed by Bayer, is an investigational treatment for severe hemophilia A. It is a PEGylated molecule of recombinant factor VIII in which the B-domain, a region within the factor, is deleted. The therapy is produced using a baby hamster kidney cell line (BHK-21), and has a polyethylene glycol (PEG) molecule specifically attached to an engineered cysteine residue within the factor protein.

Clinical studies with BAY 94-9027

A Phase 1 study (NCT01184820) in 14 people with severe hemophilia A demonstrated that patients were able to tolerate the drug with no production of inhibitors against the PEGylated factor. The mean the half-life of BAY 94-9027 — the time it takes for half of the drug to be eliminated by the body — was approximately 19 hours, about 1.4 times that of standard recombinant factor VIII.

Based on the results of the Phase 1 trial, an open-label, partially randomized Phase 2/3 trial (NCT01580293; PROTECT FVIII) was designed to assess the effectiveness and safety of BAY 94-9027 in 134 previously treated patients with severe hemophilia A, ages 12 to 65. Patients treated with prophylaxis (preventive treatment) before the study were eligible only for prophylactic treatment with BAY 94-9027, while those previously treated on demand could choose to continue episodic treatment or enter the prophylaxis arm.

Patients in the prophylaxis arm (114 people) received 25 IU/kg of BAY 94-9027 twice weekly for a 10-week run-in period. For the following 26 weeks, 86 of the 97 patients who had less than one breakthrough bleed were then randomized to receive a either starting dose of 45 IU/kg of BAY 94-9027 every five days (43 people) or a 60 IU/kg fixed dose of BAY 94-9027 every seven days (43 people). The other 11 people and the remaining 13 people who experienced more than one breakthrough bleed continued with 30 to 40 IU/kg of BAY 94-9027 twice weekly.

About one-quarter of the patients treated every seven days experienced one or more bleeds and their dosing frequency was increased to every five days or twice weekly. None of the patients treated every five days needed to increase their dosing frequency.

The median annualized bleeding rate (the number of bleeds a person experiences over the course of one year) on preventive treatment was 4.1 in those treated twice weekly, 1.9 in those treated every five days, and 0.96 in those who could maintain a seven-day treatment interval. Up to 91 percent of bleeding episodes were controlled with one or two infusions. No patient developed anti-FVIII neutralizing antibodies.

The data demonstrates the efficacy of BAY 94-9027 for preventive treatment but suggests that once-weekly treatment would not provide optimum bleed prevention for the majority of patients.

A Phase 3 multicenter, open-label, non-randomized trial (NCT01775618; PROTECT VIII Kids) is currently underway to investigate the effectiveness and safety of BAY 94-9027 in previously treated children with severe hemophilia A who are younger than 12.

The study has been recently completed but final results have not yet been published in full. Children started prophylaxis with BAY 94-9027 either at 25 IU/kg twice weekly, 45 IU/kg every five days, or at 60 IU/kg once weekly, at the investigator’s discretion.

As of the latest report, 61 children were treated (32 of them younger than 6 years old) and eight of 15 (53 percent) of those who started once-weekly treatment needed to increase the dosing frequency to either every five days (six children) or twice-weekly (two children). The median annualized bleeding rate across all treatment arms was 2.87 for all bleeds, zero for spontaneous bleeds, and zero for joint bleeds.

Almost all bleeds (92 percent) were successfully treated with one or two infusions; a quarter of the children had no bleeds during the study period. Three children who experienced hypersensitivity symptoms and five who showed loss of efficacy of BAY 94-9026 were withdrawn from the study. No anti-FVIII inhibitors were detected.

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