• Evaluate the safety and efficacy of BeneFIX in PTPs with severe and moderate haemophilia B for the treatment or prevention of bleeding episodes²

• The study comprised pharmacokinetic assessment, assessment of thrombogenicity and safety and efficacy during home treatment and management of surgical procedures. The PK assessment was repeated every 6 months, with routine clinical and laboratory evaluations at 3-month intervals. The planned study duration for each participant was 2 years²

56 patients from at 20 sites throughout North America and Europe were enrolled and received BeneFIX.²

Outcomes:

• A total of 2758 infusions were administered for on-demand treatment of 1796 hemorrhages².
• All bleeding episodes were controlled exclusively with BeneFIX using standard dosing intervals².

• Most bleeding episodes (80.9%) were controlled with one infusion²                                                         

BeneFIX is clinically effective in the treatment and prevention of bleeding in individuals with hemophilia B.²

• To evaluate the safety and efficacy of reformulated BeneFIX for treatment and prevention of       haemorrhages in PTPs with moderately severe to severe haemophilia B³  
• To evaluate bioequivalence between BeneFIX and reformulated BeneFIX³  
• Double-blind, randomised, PK crossover study³                                                                                                                                                                           

34 subjects were randomised to receive a single 75 IU/ kg dosage of BeneFIX or reformulated BeneFIX³

• 77/95 bleeds (81.1%) were resolved with a single infusion of reformulated BeneFIX³ 
• Treatment response to the first reformulated BeneFIX infusion was rated “excellent” or “good  85.3% of haemorrhages^†        
• More than half of subjects using reformulated BeneFIX for routine prophylaxis (11 of 17, 64.7%)    had no spontaneous bleeding episodes during their 6–12 month-course of prophylactic treatment^3.

BeneFIX has been reformulated and the reformulated product is effective for treatment of haemophilia B.³

• To better characterize PK parameters, both initially and after repeated BeneFIX exposure with   usual hemophilia B care (including on-demand treatment, routine prophylaxis, and surgical prophylaxis) and collect additional efficacy and safety data⁴                                                                                                                                                                                                                                                                                                                                                                                  
• To collect additional efficacy and safety data⁴                                                                                                                                                                                                                                                                                                                                                                                                                
• To examine the relationship between patient body weight and BMI and Cmax of FIX activity⁴                                                                                                                                                                                                                                   
• Prospective, open-label, non-randomised, multinational, multicentre study⁴               

• 23 patients were enrolled; 21 of those had ≥30 exposure days to BeneFIX and were evaluable for   efficacy⁴                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
• Eligible participants were aged at least 12 years, had moderately severe to severe hemophilia B     (FIX activity [FIX:C] ≤ 2%)⁴

• A total of 103 bleeding events were reported for patients receiving on-demand treatment; 54      were  spontaneous events and 49 were injury related⁴      
• 73 bleeding events (71%) occurred in 9 patients while following the on-demand treatment                regimen (monthly bleeding rate, 1.2)⁴      
• 30 bleeding events (13 spontaneous and 17 due to injury) were reported in 13 patients while using   routine prophylaxis (mean monthly bleeding rate, 0.4) 
• Regardless of location, 54 of the103 bleeding events (52%) resolved with a single infusion⁴      
• Ratings of response‡ to the initial infusion for on-demand treatment were “excellent” or “good” for 87(84%) of the 103 bleeding events⁴

BeneFIX was effective for on-demand treatment, routine prophylaxis, and surgical prophylaxis in previously treated patients with moderately severe to severe hemophilia B.⁴

*On demand dose: The calculation of the required dose of BeneFIX can be based on the finding that one unit of factor IX activity per kg body weight is expected to increase the circulating level of factor IX, an average of 0.8 IU/dL (range from 0.4 to 1.4 IU/ dL) in patients ≥ 12 years. 
 

The required dosage is determined using the following formula: Number of factor IX IU required = body weight (in kg) X desired factor IX increase (%) or (IU/dL) X reciprocal of observed recovery
 

Prophylaxis dose: BeneFIX may be administered for long term prophylaxis against bleeding in patients with severe haemophilia B. In a clinical study for routine secondary prophylaxis the average dose for PTP was 40 IU/kg (range 13 to 78 IU/kg) at intervals of 3 to 4 days.¹
 

^†Excellent: dramatic response with abrupt pain relief and clear reduction in joint or haemorrhage site size; Good: pain relief or reduction in haemorrhage site size which was delayed or required additional infusion for resolution.³
 

^‡Response was evaluated by the patient or caregiver or by the investigator using a 4-point scale.⁴     
 

BMI: body mass index; Cmax: peak plasma concentration; FIX: factor IX; IU: international unit; PK: pharmacokinetic; PTP: previously treated patient

• Evaluate safety and efficacy of rFIX for usual haemophilia B care in children <6 years old, incluse    in the setting of routine prophylaxis²                                                                                                                                                               
• International, open-label, multi-centre, prospective study²                                                                                                                                        

• Eligible patients had severe haemophilia B (FIX activity ≤1%)²                                                                                
• 25 patients received at least one dose of BeneFIX²                                                                                                                                                                                                                                              

• 77% of children on routine prophylaxis* with BeneFIX had no spontaneous hemorrhages and seven patients (32%)                                                                                                                 
• had no bleeding episodes at all²                                                                                                                                                               
• 20/22 patients (91%) had ≤1 joint hemorrhage during the course of prophylaxis²                                                                                                                                                                                                                                                                         

Regular BeneFIX infusions effectively controlled and prevented hemorrhages in the 22 efficacy evaluable subjects, all of whom were prescribed routine prophylaxis.²

*Mean dosage in pediatric population (± standard deviation) for prophylaxis was 64.6 (±21.3) IU/kg.² Please refer to the local label for approved dosages.                                                                                                  

FIX: factor IX; IU: international unit; PTP: previously treated patient; PUPs: Previously untreated patients.

• Determine the safety and efficacy of BeneFIX in the surgical setting, with acute, short-term higher intensity treatment²

BeneFIX was evaluated in 28 subjects with FIX deficiency (including 26 with mild, moderate or severe haemophilia B and two haemophilia B carriers) undergoing 36 surgical procedures²

Outcomes:

• The clinical responses to rFIX were rated excellent or good by subjective assessment by the           physician/ surgeon or by the subject in 34 of 35 procedures (97%).²  
• Physicians rated the response to BeneFIX as “excellent” or “good” in all pre- and post-operative      cases*²

BeneFIX was found to be effective in achieving haemostasis in subjects with FIX deficiency undergoing surgery²

^*Excellent: the response was as satisfactory, with as much and as rapid an improvement as the best responses with other FIX products for similar bleeds or procedures; Good: the response was as satisfactory, with as much and as rapid an improvement as most responses with other FIX products for similar bleeds or procedures.²

FIX: factor IX; rFIX: recombinant factor IX.