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Patients under 12 years

Verifying the safety and efficacy of ADYNOVATE® in children under 12

The phase 3 prospective, uncontrolled, multicenter, open-label, pediatric study (N=73) evaluated the efficacy, PK (as compared to ADVATE® [Antihemophilic Factor (Recombinant)]), and safety of ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated] twice-weekly prophylaxis and determined hemostatic efficacy in the treatment of bleeding episodes for 6 months. Sixty-six patients (32 patients aged <6 years and 34 patients aged 6 to <12 years) received 40-60 IU/kg of ADYNOVATE prophylactically, twice-weekly.1,2

The primary endpoint was to assess the development of FVIII inhibitors. Inhibitors were defined as ≥0.6 BU using the Nijmegen modification of the Bethesda assay.3

Established safety profile in children under 12

The pediatric study met its primary endpoint, as no previously treated children developed inhibitory antibodies to ADYNOVATE® [Antihemophilic Factor (Recombinant), PEGylated].1,3

5 pediatric previously treated patients developed IgG antibodies against PEG-FVIII: transiently (n=2), binding antibodies at the completion of the study (n=2), and developed binding antibodies during the study and positive at completion with decreasing titer (n=1). For all 3 subjects who developed binding antibodies, no conclusion can be drawn whether these antibodies are of transient or persistent nature.1,3

One pediatric previously untreated patient from an ongoing study, who received at least one infusion of ADYNOVATE, developed neutralizing antibodies to FVIII.1

*Inhibitors defined as ≥0.6 BU using the Nijmegen modification of the Bethesda assay.3
†From completed and ongoing studies of pediatric previously treated patients.
‡Pediatric previously treated patients defined as: <6 years of age with ≥50 EDs, ≥6 to <12 years of age with ≥150 EDs.1

SELECTED IMPORTANT RISK INFORMATION

WARNINGS & PRECAUTIONS
Neutralizing Antibodies

Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.

Effective coverage against bleeds

During the 6-month clinical study in children under 12 receiving twice-weekly prophylaxis treatment1,2:


Results are from the full analysis set.3

ABR=annualized bleed rate.

IQR=interquartile range; the range of values of the variable in a statistical distribution that lies between the upper and lower quartiles.4

SELECTED IMPORTANT RISK INFORMATION

WARNINGS & PRECAUTIONS
Hypersensitivity Reactions

Hypersensitivity reactions are possible with ADYNOVATE. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with other recombinant antihemophilic factor VIII products, including the parent molecule, ADVATE. Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

ADVERSE REACTIONS
The most common adverse reactions (≥1% of subjects) reported in the clinical studies were headache and nausea.

Prophylaxis helped some children under 12 stay bleed-free

During the 6-month prophylaxis clinical study in children under 12 (N=66)1,2:

Effective bleed control in children under 12

When bleeds did occur, the majority were controlled with a single infusion of ADYNOVATE® [Antihemophilic Factor
(Recombinant), PEGylated].1,2

In the clinical trial, bleeding episodes controlled:

*Excellent defined as full relief of pain and objective signs of bleeding cessation; Good defined as definite pain relief and/or improvement in signs of bleeding.1

SELECTED IMPORTANT RISK INFORMATION

CONTRAINDICATIONS
ADYNOVATE is contraindicated in patients who have had prior anaphylactic reaction to ADYNOVATE, to the parent molecule (ADVATE [Antihemophilic Factor (Recombinant)]), mouse or hamster protein, or excipients of ADYNOVATE (e.g. Tris, mannitol, trehalose, glutathione, and/or polysorbate 80).

Designed to extend FVIII circulation time

In the pediatric phase III prospective, uncontrolled, multicenter, open-label study, a PK comparison of ADYNOVATE® [Antihemophilic Factor (Recombinant), PEGylated] vs ADVATE® [Antihemophilic Factor (Recombinant)] was conducted in 31 children prior to initiation of prophylactic treatment with ADYNOVATE.2

The extended terminal half-life of ADYNOVATE was 1.3X–1.5X longer than that of ADVATE (based on one-stage clotting and chromogenic assay, respectively).2,3

Pharmacokinetic studies in children (<12 years) have demonstrated higher clearance, a shorter half-life, and lower incremental recovery of factor VIII compared to adults. Because clearance (based on per kg body weight) has been demonstrated to be higher in children (<12 years), dose adjustment or more frequent dosing based on per kg body weight may be needed in this population.1

PEGylation Technology* was deliberately chosen because

  • It allows for half-life extension while maintaining the integrity of the ADVATE protein5,6
  • It has a long history of use as an extension technology7

*Proprietary PEGylation Technology exclusively licensed from Nektar Therapeutics.

Detailed Important Risk Information
Prescribing Information (PI)
ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated] Important Information
Indications

ADYNOVATE, Antihemophilic Factor (Recombinant), PEGylated, is a human antihemophilic factor indicated in children and adults with hemophilia A (congenital factor VIII deficiency) for:

  • On-demand treatment and control of bleeding episodes
  • Perioperative management
  • Routine prophylaxis to reduce the frequency of bleeding episodes

Limitation of Use

ADYNOVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION


Click here for ADYNOVATE full Prescribing Information.



ADVATE [Antihemophilic Factor (Recombinant)] Important Information
Indications

ADVATE is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A (congenital factor VIII deficiency) for:

  • Control and prevention of bleeding episodes.
  • Perioperative management.
  • Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

ADVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

Neutralizing Antibodies
Neutralizing antibodies (inhibitors) have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs). Monitor all patients for the development of factor VIII inhibitors by appropriate clinical observation and laboratory testing. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor VIII inhibitor concentration.

Click here for ADVATE full Prescribing Information.