TORONTO—The antihemophilic factor turoctocog alfa is safe and effective long-term, according to interim data from the phase 3 guardian 2 trial.
With more than 4 years of safety data, researchers have found turoctocog alfa to be well-tolerated in patients with hemophilia A.
The median annualized bleeding rate for patients on prophylactic treatment was 1.56 bleeds per patient per year. For patients who received turoctocog alfa on demand, a single injection stopped all bleeds.
And none of the patients developed factor VIII (FVIII) inhibitors.
Margareth Ozelo, MD, PhD, of the University of Campinas in Sao Paulo, Brazil and her colleagues presented these data at the ISTH 2015 Congress (abstract PO251-WED). The research is sponsored by Novo Nordisk, the company developing turoctocog alfa (as NovoEight).
Turoctocog alfa is a B-domain truncated recombinant human coagulation FVIII product indicated for the treatment and prevention of bleeding in patients with hemophilia A. The ongoing guardian 2 trial is a prospective safety and efficacy extension trial of the guardian 1 and guardian 3 studies.
Two hundred patients received turoctocog alfa in guardian 2. They had severe hemophilia A (FVIII activity ≤ 1%), no history of inhibitors, and had completed guardian 1, guardian 3, or a third pharmacokinetics trial. The patients’ mean age at first turoctocog alfa injection was 22.3 ± 14.4 years.
In guardian 1 and guardian 3, all patients switched from other FVIII products to turoctocog alfa prophylaxis every second day (adults/adolescents, 20–40 IU/kg; children, 25–50 IU/kg), or 3 times weekly (adults/adolescents, 20–50 IU/kg; children 25–60 IU/kg). Patients also received turoctocog alfa when bleeds arose.
Of the 200 patients enrolled on guardian 2, 133 were still participating in the trial at the interim cutoff date, December 31, 2013.
The interim analysis includes data for 451.6 patient-years and 72,320 days of exposure to turoctocog alfa. The total number of exposure days was 364.5
(range, 1-762) per patient for prophylaxis and 23.8 (range, 1-90) per patient for on-demand treatment.
The mean number of turoctocog alfa doses was 368.3 (range, 1-766) per patient for prophylaxis and 24.2 (range, 1-90) per patient for on-demand treatment.
Safety results
At the interim cutoff, none of the patients had developed FVIII inhibitors. Adverse events occurred in 84% of patients (n=168). The most common were
headache, nasopharyngitis, upper respiratory tract infection, and arthralgia.
Eight adverse events were considered possibly or probably related to turoctocog alfa in 5 patients (2.5%). These events were mild or moderate and included local swelling (n=1), increased aspartate aminotransferase (n=1), increased alanine aminotransferase (n=1), pain in extremity (n=1), musculoskeletal pain (n=1), lichenoid keratosis (n=1), and arthropathy (n=2).
There were 29 serious adverse events that were considered unlikely to be treatment-related. This included a death from subdural hemorrhage.
Efficacy results
For patients on prophylactic treatment (n=197), the median annualized bleeding rate was 1.56 bleeds per patient per year for all bleeds. It was 0.50 for
spontaneous bleeds, 0.49 for traumatic bleeds, 0.93 for joint bleeds, and 0.35 for nonjoint bleeds.
The success rate for treating bleeds during prophylaxis was 89.4%, and 90% of all bleeding episodes were successfully treated with 1 or 2 infusions of
turoctocog alfa. As for on-demand treatment, a single injection stopped all 73 bleeds.
“These interim results provide an extension to the body of evidence supporting the long-term use of NovoEight,” Dr Ozelo said. “For people with hemophilia A, finding treatments that are effective at preventing bleeding episodes long-term is essential.”
