Turoctocog alfa, a recombinant Factor VIII molecule, was effective in preventing bleeding episodes and was well tolerated in more than 200 males with hemophilia A who were part of the Guardian 2 extension trial.
The open label, phase 3bincluded patients who had completed the Guardian 1 or Guardian 3 phase 1 pharmacokinetics trials and who chose to continue prophylaxis with turoctocog alfa ( ).
In total, 214 patients were enrolled and 213 were exposed to treatment. Prophylaxis was given as a standard dose level of 20-50 IU/kg once every second day or 20-60 IU/kg three times weekly. Less frequent prophylaxis was available at 40-60 IU/kg twice weekly or once every third day. For on-demand treatment, the recommended dose level was 20-50 IU/kg.
“The final results of guardian 2 are consistent with data from previous interim analyses,”, of the University of Iowa, Iowa City, and his colleagues wrote in . “Turoctocog alfa was well tolerated, with no unexpected safety signals and no development of FVIII inhibitors.”
Among the 207 patients on prophylaxis, 1,782 bleeds were reported. The overall median annualized bleeding rate (ABR) for this group was 1.37. More than 88% of these bleeds were stopped with one or two injections and the success rate for treatment of bleeds was more than 90%.
The median ABR dropped to zero, with a range of 0.00‐9.91, for the 27 patients who were on the less-frequent prophylaxis regimen. In this group, more than 75% of the 34 bleeds that occurred were stopped with one injection and the success rate for treatment of bleeds was about 94%.
“These data suggest a subset of patients might be well managed with less‐frequent dosing,” the researchers wrote.
For the 19 patients who received on-demand treatment, there were 391 bleeds reported. The overall median ABR was 30.44. Nearly 80% of bleeds were stopped with one injection and more than 15% with two injections. The treatment success rate in this group was more than 96%.
There were no Factor VIII inhibitors reported in the extension trial.
In total, there were 1,260 adverse events reported for 183 patients, corresponding to less than two adverse events per patients per years of exposure to the treatment.
The most common adverse event, seen in 14.6% of patients, was nasopharyngitis. Serious adverse events occurred in 18.3% of patients but all expect one event was deemed unlikely to be related to treatment. The one fatal event in the trial was deemed unlikely to be related to treatment.
The study was funded by Novo Nordisk. Dr. Lentz reported being a paid consultant to Novo Nordisk and receiving research funding from the company.
SOURCE: Lentz SR et al. .