For on-demand bleed control, surgery and routine prophylaxis in adults and children with hemophilia A. Not for von Willebrand disease.
Proven reliability in treating bleeds
Data from one of the largest clinical trial programs of a recombinant FVIII showed Novoeight® to be effective in adults, adolescents, and children. The guardian™ clinical trial program included 238 previously treated patients and more than 130,000 exposure days.1-3
Proven effective in adults, adolescents, and children
All patients
(0–65 years old)
median bleeds per year, per guardian™1 and 34
Children
(≤11 years old)
median bleeds per year, per guardian™32
Results of an initial clinical trial studying the effectiveness and safety in children
Long-term safety trial
(0-65 years old)
median bleeds per year, per guardian™24
The majority of patients continued in a safety extension trial
ABR=annualized bleed rate.
Results from guardian™ 1 and guardian™ 3 pivotal trials1,2,5
N=25
Success was defined as “excellent” or “good” haemostatic outcome.5
Novoeight® offers an established safety profile
in a clinical trial of PUPs, 42.9% developed inhibitors4,a
Development of activity-neutralizing antibodies (inhibitors) may occur. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, perform an assay that measures factor VIII inhibitor concentration.4
- Safety results consistent among adults, adolescents, and children1,2
- The most frequently reported adverse reactions in previously treated patients were injection site reactions (1.0%) and pyrexia (1.0%)4
- Adverse reactions reported during postmarketing period were similar to those observed during clinical trials4
PUP=previously untreated patient
a59 PUPs with severe hemophilia A (factor VIII levels ≤1%) received at least one dose of Novoeight® as part of either routine prophylaxis or on-demand treatment of bleeding episodes. Patients developed inhibitors with a mean of 14.1 exposure days at the time of the first positive inhibitor test. High-risk genetic mutations were identified in 91.7% of the overall inhibitors and 93.3% of the high titer inhibitors.4
Study designs
Lentz et al (2013)
guardian™1 phase 3 trial1
Patients: 150 male, previously treated patients aged 12–65 years with severe hemophilia A (FVIII activity ≤1%) and without inhibitors to FVIII (<0.6 BU). Prior to this trial, all patients had at least 150 exposure days to any FVIII product. Exposure day is defined as every day where the patient received at least one dose of FVIII.
Study design: Multicenter, multinational, open-label, and non-controlled. Patients infused Novoeight® prophylactically, either 20–40 IU/kg every second day or 20–50 IU/kg three times weekly. Dose for all patients started at 20 IU/kg and was adjusted as necessary at the investigator’s discretion. For breakthrough bleeds, dosage was based on achieving a plasma FVIII activity level of 0.50 IU/mL, with treatment occurring as soon as bleeds were identified. For the 150 patients, mean exposure was 85 exposure days (based on a range of 11 to 172 exposure days).
Primary endpoint: The incidence rate of FVIII inhibitors, measured by positive results for inhibitors (≥0.6 BU) in two consecutive test samples analyzed at a central laboratory.
Lentz et al (2018)
guardian™2 phase 3b extension trial
Patients: Previously treated pediatric patients (0–11 years), adolescents (12-17 years), and adults (18-65 years) with severe hemophilia A (FVIII activity ≤1%) and without inhibitors. Patients had completed earlier phase 1 pharmacokinetic trials (guardian™1 or guardian™3) and chose to continue taking Novoeight® as prophylaxis (n=207) and/or on-demand treatment (n=19).1,2,6
Study design: Non‐randomized, open‐label, multicenter, multinational, single‐arm, safety and efficacy extension trial. Patients infused Novoeight® prophylactically, with standard dosing (25–50 IU/kg every second day or 20–60 IU/kg three times weekly) or less-frequent dosing (40-60 IU/kg twice weekly or once every third day). The recommended dose level for on-demand treatment was 20-50 IU/kg.6
Primary endpoint: The incidence rate of FVIII inhibitors (≥0.6 BU).6
Secondary endpoint: Frequency of adverse events and serious adverse events.6
Kulkarni et al
guardian™3 phase 3 trial2
Patients: Male, previously treated patients aged 0–11 years (n=63) with severe hemophilia A (FVIII activity ≤1%) and without inhibitors. Prior to this trial, all patients had at least 50 exposure days to any FVIII product.
Study design: Multinational, open-label, and uncontrolled. Patients infused Novoeight® prophylactically, either 25–50 IU/kg every second day or 20–60 IU/kg three times weekly. For breakthrough bleeds, dosage was based on achieving a plasma FVIII activity level of 0.50 IU/mL, with treatment occurring as soon as bleeds were identified. For the 63 patients, mean exposure was 60 exposure days (based on a range of 20 to 104 exposure days).
Primary endpoint: The incidence rate of FVIII inhibitors, measured by positive results for inhibitors (≥0.6 BU) in two consecutive test samples analyzed at a central laboratory.
Santagostino et al
Surgery-related efficacy and safety (guardian™ clinical trial program)5
Patients: Male patients participating in guardian™1 (adults and adolescents), guardian™3 (children), or guardian™2 (safety and efficacy extension) trials. Data shown is from guardian™1 and guardian™3 only. All patients had severe hemophilia A (FVIII ≤ 1%) without inhibitors and were previously treated with at least 150 exposure days (adolescents and adults) or at least 50 exposure days (children) to any FVIII product.
Study design: Thirty-three male patients (7 children, 1 adolescent and 25 adults) underwent a total of 15 major and 26 minor surgical procedures. Patients received Novoeight® as bolus injections or continuous infusion, at dosage determined by the investigator, including a loading dose immediately prior to surgery.
Endpoints: The safety and efficacy of Novoeight® as perioperative treatment was assessed as part of the secondary objectives of the guardian™ trial program. Efficacy assessment included hemostatic response, which was evaluated at the end of the surgical procedure. A hemostatic response rated as “excellent” or “good” was considered treatment success.
Clinical trial with previously untreated patients (PUPs)4
Patients: Previously untreated children (n=59) below 6 years of age with severe hemophilia A (factor VIII activity ≤1%) and no history of FVIII inhibitors.
Study design: This trial evaluated the safety and efficacy of Novoeight® in routine prophylaxis and the on-demand treatment and control of breakthrough bleeds. Subjects received Novoeight® at standard recommended dose levels. Breakthrough bleeds were treated at the investigator’s discretion, aiming for a FVIII activity level above 0.5 IU/mL.
Primary endpoint: Incidence rate of FVIII inhibitors.
Efficacy endpoints: Hemostatic effect during treatment of bleeding episodes, number of infusions needed to stop a bleeding episode, and annualized bleeding rate (ABR).
Dosing guidelines for Novoeight®
Refer to our dosing tables for recommendations.
Important Safety Information for Novoeight®
Contraindications
- Do not use in patients who have had life-threatening hypersensitivity reactions, including anaphylaxis, to Novoeight® or its components, including hamster proteins
Warnings and Precautions
- Anaphylaxis and severe hypersensitivity reactions are possible. Patients may develop hypersensitivity to hamster proteins, which are present in trace amounts in the product. Should symptoms occur, discontinue Novoeight® and administer appropriate treatment
- Development of activity-neutralizing antibodies (inhibitors) may occur. Previously untreated patients (PUPs) are at greatest risk for inhibitor development with all factor VIII products. Inhibitors have been reported following administration of Novoeight® in PUPs. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, perform testing for factor VIII inhibitors
Adverse Reactions
- The most frequently reported adverse reactions (≥1%) were inhibitors in Previously Untreated Patients (PUPs), injection site reactions, and pyrexia.
Please click here for Novoeight® Prescribing Information.
Indications and Usage
Novoeight® (antihemophilic factor, recombinant) is indicated for use in adults and children with hemophilia A for on-demand treatment and control of bleeding episodes, perioperative management, and routine prophylaxis to reduce the frequency of bleeding episodes.
- Novoeight® is not indicated for the treatment of von Willebrand disease
Important Safety Information for Novoeight®
Contraindications
- Do not use in patients who have had life-threatening hypersensitivity reactions, including anaphylaxis, to Novoeight® or its components, including hamster proteins
Warnings and Precautions
- Anaphylaxis and severe hypersensitivity reactions are possible. Patients may develop hypersensitivity to hamster proteins, which are present in trace amounts in the product. Should symptoms occur, discontinue Novoeight® and administer appropriate treatment
- Development of activity-neutralizing antibodies (inhibitors) may occur. Previously untreated patients (PUPs) are at greatest risk for inhibitor development with all factor VIII products. Inhibitors have been reported following administration of Novoeight® in PUPs. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, perform testing for factor VIII inhibitors
Adverse Reactions
- The most frequently reported adverse reactions (≥1%) were inhibitors in Previously Untreated Patients (PUPs), injection site reactions, and pyrexia.
Please click here for Novoeight® Prescribing Information.
Indications and Usage
Novoeight® (antihemophilic factor, recombinant) is indicated for use in adults and children with hemophilia A for on-demand treatment and control of bleeding episodes, perioperative management, and routine prophylaxis to reduce the frequency of bleeding episodes.
- Novoeight® is not indicated for the treatment of von Willebrand disease
References
1. Lentz SR, Misgav M, Ozelo M, et al. Results from a large multinational clinical trial (guardian™1) using prophylactic treatment with turoctocog alfa in adolescent and adult patients with severe haemophilia A: safety and efficacy. Haemophilia. 2013;19:691-697.
2. Kulkarni R, Karim FA, Glamocanin S, et al. Results from a large multinational clinical trial (guardian™3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A: safety, efficacy and pharmacokinetics. Haemophilia. 2013;19(5):698-705.
3. Lentz S, Janic D, Ozelo MC, et al. End-of-trial results from a large multinational extension trial (guardian™2) using turoctocog alfa for prophylaxis and treatment of bleeding in patients with severe haemophilia A. Poster presented at: International Society on Thrombosis and Haemostasis 26th Biennial Congress Meeting; July 8-13, 2017; Berlin, Germany.
4. Novoeight® [package insert]. Plainsboro, NJ: Novo Nordisk Inc.
5. Santagostino E, Lentz SR, Misgav M, et al. Safety and efficacy of turoctocog alfa (NovoEight®) during surgery in patients with haemophilia A: results from the multinational guardian™ clinical trials. Haemophilia. 2015;21(1):34-40.
6. Lentz SR, Janic D, Kavakli K, et al. 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. Haemophilia. 2018 Nov;24(6):e391-e394.