Safety and Efficacy of nonacog beta pegol (N9-GP) in Previously Untreated Patients with Haemophilia B

Children are among those who might benefit significantly from prophylaxis with
N9-GP. The most commonly used products for the treatment of haemophilia B have
short half-life of 18 19 hours demanding frequent dosing for prophylaxis of
bleeding episodes, with 2-3 injections a week. The prolonged half-life of N9-GP
offers an expected advantage of once weekly or potentially even less frequent
injections, which reduces the burden of treatment while maintaining effective
haemostasis. Likewise it may promote adherence to therapy due to less frequent
injections. The pivotal phase 3 trial (NN7999-3747) demonstrated a prophylactic
protection of 40 IU/kg N9-GP once weekly and showed that 99% of bleeding
episodes in the 40 IU/kg arm were stopped with a single dose of N9-GP.
Furthermore EMA requires separate investigation of PUPs as part of the
development programme initiated before market authorisation (MA) gets obtained.
A final guideline on the clinical investigation of recombinant and human
plasma-derived factor IX products from the Committee for Medical Product for
Human Use (CHMP), describes the mandatory components for trials in PUP. In some
countries outside the EU, PUP Paediatric investigation is necessary to achieve
labelled indication for all children.

Primary Objective
- To evaluate immunogenicity of N9-GP (nonacog beta pegol)

Secondary Objectives
- To evaluate safety of N9-GP (nonacog beta pegol)

- To evaluate efficacy of N9-GP (nonacog beta pegol)
* in long-term prophylaxis treatment
* in the treatment of bleeding episodes
* through the surrogate marker: FIX activity
* through monitoring of number of doses and consumption of N9-GP

The trial is an open label, single-arm, multinational, non-controlled
confirmatory trial investigating safety and efficacy of N9-GP in prophylaxis
and treatment of breakthrough bleeding episodes in haemophilia B previously
untreated patients with FIX activity <= 2%.The trial has one treatment arm in
which at least 40 patients should achieve 100 exposure days with N9-GP.
The European medicines agency requires submission of safety and efficacy data
from a minimum of 50 exposure days in at least 20 patients for approval of the
indication in previously untreated patients, with a post-approval extension
phase according to guideline to follow-up in at least 40 patients, for a
minimum of 100 exposure days. When the first 20 patients have reached at least
50 exposure days, the analysis and evaluation for the main trial report will be
performed. All patients continue in the extension phase for the purpose of
acquiring data for a minimum of 100 exposure days in at least 40 patients.

Injection of 40 IU/kg N9-GP administered every 7th day to prevent bleeding
episodes, and in addition immediate treatment with 40 IU/kg N9-GP in case of a
mild or moderate bleeding or 80 IU/kg in case of a severe bleeding episode.

Occasionally, temporary discomfort, bruising, bleeding or swelling at the site
of needle insertion for the withdrawal of the blood samples or trial medicine
injection may occur. There is also a very small risk of infection at the place
where the needle goes into your son*s vein.
There is also a risk of side effects. The primary concern in PUPs is the risk
of development of neutralizing antibodies to FIX (inhibitors). Development of
binding antibodies and inhibitors will be monitored closely throughout the
trial.
Hypersensitivity reactions may occur with the administration of N9-GP, as with
any protein injected intravenously. Patients will be closely monitored for
development of hypersensitivity reactions, in relation to the first 20
exposures with N9-GP.
No unexpected safety issues have been identified in the completed and ongoing
clinical trials with N9-GP and the risk/benefit ratio for N9-GP is therefore
expected to be favorable.