Novoeight Safe, Effective in Hemophilia A Patients Over Long Term, Phase 3b Trial Shows

Long-term treatment with Novoeight (turoctocog alfa) is safe and effective at preventing bleeding episodes in patients with hemophilia A of all ages who had already received prior treatment, a Phase 3b extension trial shows.

The study, “Long‐term safety and efficacy of turoctocog alfa in prophylaxis and treatment of bleeding episodes in severe haemophilia A: Final results from the guardian 2 extension trial,” was published in Haemophilia.

Hemophilia is a genetic blood disorder that affects the body’s ability to make blood clots to prevent excessive bleeding. In hemophilia A, this inability of the blood to clot is caused by the lack of a specific clotting protein, called factor VIII (FVIII).

Current treatments for hemophilia A are based on providing the missing FVIII to patients as a prophylaxis, or preventive measure, to avoid spontaneous bleeding episodes.

Novoeight, a third-generation recombinant (lab-made) FVIII developed by Novo Nordisk, is approved by the U.S. Food and Drug Administration for the treatment and prevention of spontaneous bleeding in patients with hemophilia A.

In two previous Phase 3 trials — guardian 1 (NCT00840086) and guardian 3 (NCT01138501) — Novoeight achieved positive results in both adults/adolescents and children with severe hemophilia A who had already received prior treatment, respectively.

The non-randomized, open-label, multicenter Phase 3b extension study (NCT00984126), called guardian 2, focused on assessing the long-term safety and efficacy of Novoeight in pretreated patients with severe hemophilia A.

All patients who completed guardian 1 or guardian 3 or Phase 1 pharmacokinetics (drug properties) trials and wished to receive prophylaxis with Novoeight in the extension trial were eligible to participate in the study. It enrolled 213 hemophilia A patients — 207 received Novoeight prophylactically (including 27 on a less-frequent regimen) and 19 on an on-demand basis.

The primary safety goal of the study consisted of evaluating the number of patients who developed FVIII inhibitors. Efficacy goals included the annualized bleeding rate (ABR, or the number of bleeding episodes per year) during prophylaxis, hemostatic (blood-clotting) response in bleeding treatment, and number of Novoeight injections required to treat bleeding episodes.

Patients receiving Novoeight prophylactically had an overall median ABR of 1.37 spontaneous bleeds per year. Most of the bleeding episodes (88.2%) were controlled with one to two injections of Novoeight, and the treatment reached an overall success rate of 90.2%, indicating that Novoeight successfully prevented most bleeding episodes when administered prophylactically.

“The guardian 2 trial also evaluated a less-frequent dosing regimen (twice weekly or every third day) in selected patients, which demonstrated efficacy, with an overall median ABR of 0.00, and a treatment success rate of 94.1%. These data suggest a subset of patients might be well managed with less-frequent dosing,” the researchers wrote.

Conversely, patients receiving Novoeight on an on-demand basis had an overall median ABR of 30.44 spontaneous bleeds per year. As in patients on prophylaxis, most of the bleeding episodes (94.9%) were controlled with one to two injections of Novoeight, and the treatment reached an overall success rate of 96.7%, further demonstrating that Novoeight is highly effective in the treatment of spontaneous bleeding episodes.

Treatment with Novoeight was considered safe and well-tolerated. None of the patients developed FVIII inhibitors over the course of the study.

A total of 1,260 side effects were reported in 85.9% of the patients, the most common of which was nasopharyngitis, otherwise known as the common cold, in 14.6% of patients. Only 47 serious adverse effects in 18.3% of the patients were described, and all except one were considered ‘”unlikely'” to be related with Novoeight treatment.