Bayer announces positive results from PROTECT VIII trial

The study met its primary objective of protection from bleeds with fewer infusions. In the study, the site-specific PEGylated factor VIII provided protection from bleeds when used prophylactically every seven days, every five days, and twice per week. The compound was also effective for treatment of acute and breakthrough bleeds with 91% of events resolved with one or two infusions.

Bayer HealthCare global development head and executive committee member Dr Joerg Moeller noted the company is pleased that the company’s site-specific PEGylated factor VIII has been shown to provide longer-lasting protection from bleeds. Reducing the significant burden associated with frequent infusions has long been a key goal of the entire hemophilia community.

"This compound may lead to improvements in long-term outcomes and quality of life for people with hemophilia A," Dr Moeller added.

The current standard treatment for severe hemophilia A is regularly scheduled prophylactic infusion of factor VIII to keep levels high enough to prevent bleeding. Due to the short half-life of currently marketed factor VIII products, prophylaxis may require treatment as often as every other day.

Bayer’s compound is engineered to extend the circulating half-life while preserving full biologic activity through site-specific pegylation. This site-specific pegylation is achieved by inserting a single cysteine (amino acid) on the factor VIII surface, which serves as an attachment site for a polyethylene glycol (PEG) polymer.

Detailed data are scheduled for presentation at the World Federation of Hemophilia Meeting in May 2014 in Melbourne, Australia. Bayer plans to submit marketing authorization applications to regulatory authorities in the US, Europe and other countries in the second half of 2015. Evaluation of safety and efficacy during major surgery and PROTECT Kids in pediatric patients are ongoing, and a study in previously untreated patients is planned.

PROTECT VIII (PROphylaxis in hemophilia A patienTs via directly pEgylated long-aCTing rFVIII) is a multicenter, multinational, partially randomized, open-label trial with four treatment arms evaluating the safety and efficacy of the site-specific PEGylated factor VIII in previously treated adults and adolescents with severe hemophilia A.

A total of 134 subjects were treated in the study. 88% of subjects met the pre-defined criterion of bleeding control in the ten-week initial assessment period and qualified for randomization. All subjects receiving infusion every five days (n=43) remained in this treatment arm. 44% of subjects in the every-five-day treatment arm experienced no bleeds.

A median annualized bleeding rate (ABR) of 1.9 was observed in this treatment arm. 74% of the subjects receiving infusion every seven days (n=43) remained in their treatment arm. 37% experienced no bleeds. A median ABR of 3.9 (including non-completers) was observed in this treatment arm. The 13 subjects who remained in the two times per week treatment arm, because of their high bleeding rate during the assessment period, reduced their median ABR from 17.4 to 4.1 following dose increase. By comparison, subjects who were treated on-demand (n=20) had a median ABR of 23.

The safety objectives were also met. The site-specific PEGylated factor VIII was well tolerated. Subjects were treated for up to 36 weeks; no inhibitors to factor VIII were confirmed. Two drug-related cases of hypersensitivity reactions were reported. One was assessed as serious, but resolved without medical intervention. No other serious drug-related adverse events were reported.