NEODOSE

INDICATIONS

Hemophilia B (congenital factor IX deficiency)

• Bleeding episodes, control and prevention: Control of bleeding was achieved with 1 dose of coagulation factor IX Fc fusion protein recombinant in the majority of patients with factor IX deficiency for prophylaxis and management of bleeding episodes. Patients with severe factor IX deficiency (age range, 12 to 71 years old; n=123) were evaluated in trials for 2 prophylactic treatment regimens (fixed weekly and individualized interval prophylaxis) and an episodic (ie, on-demand) treatment, and to determine hemostatic efficacy of coagulation factor IX Fc fusion protein recombinant for bleeding episodes and perioperatively in major surgery. In the fixed interval prophylaxis arm, patients received an initial dose of 50 international units/kg, which was then dose adjusted to maintain a factor IX trough of at least 1% to 3% above baseline (median study dose, 45.2 international units/kg). Patients in the individualized interval arm received factor IX Fc fusion protein recombinant 100 international units/kg every 10 days, with the dosing interval adjusted to maintain a factor IX trough of at least 1% to 3% greater than baseline as clinically indicated (median dosing interval, 12.5 days). Patients in the episodic treatment arm received therapy only as needed. Across all groups, 636 bleeding episodes were assessed in 114 patients, who received a median total dose per bleeding episode of 46.99 international units/kg. Most patients were treated with 1 dose (90.4%); 6.9% of patients required 2 doses, and 2.7% required 3 doses. At 8 to 12 hours after treatment, 83.7% of patients treated with 1 dose had excellent or good response, 14.7% had moderate response, and 1.6% had no response.
• Bleeding, prophylaxis: In patients with factor IX deficiency, overall annualized bleeding rates were lower in fixed weekly and individualized weekly prophylaxis groups compared with an episodic (ie, on-demand) treatment group in a small study (n=123; 12 to 71 years of age). In the fixed-interval prophylaxis arm, patients received an initial dose of 50 international units/kg, which was then adjusted to maintain a factor IX trough level of at least 1% to 3% above baseline (median dose, 45.2 international units/kg). Patients in the individualized interval arm received factor IX Fc fusion protein recombinant 100 international units/kg every 10 days, with the dosing interval adjusted to maintain a factor IX trough of at least 1% to 3% greater than baseline as clinically indicated (median dosing interval, 12.5 days). Patients in the episodic treatment arm received therapy only as needed. Across all treatment groups, 636 bleeding episodes were assessed in 114 patients, who received a median total dose of 46.99 international units per bleeding episode. During a median followup of 51.4 weeks, the annualized bleeding rates were decreased by 83% in the fixedweekly interval group and 87% in the individualized group compared with the episodic treatment group. The median annualized overall bleeding rates were 2.95% in the fixed prophylaxis group, 1.38% in the individualized prophylaxis group, and 17.69% in the episodic treatment group.
• Perioperative Management: In 14 major surgeries (eg, knee replacement, abdominal surgery, complex dental procedure) in patients with factor IX deficiency, hemostatic response of coagulation factor IX Fc fusion protein recombinant was rated as excellent (n=13) or good (n=1) in all patients, 24 hours after surgery There were 15 minor surgical procedures in 13 subjects, all without thrombotic events.

FDA APPROVED INDICATION

Coagulation Factor IX Fc fusion protein is indicated for perioperative management, ondemand treatment and control of bleeding episodes, and routine prophylaxis to decrease the frequency of bleeding episodes in adults and children with hemophilia B (congenital factor IX deficiency). The product is not indicated for induction of immune tolerance in patients with hemophilia B.

CONTRAINDICATIONS

• Known hypersensitivity to product or its excipients including sucrose, mannitol, sodium chloride, L-histidine, and polysorbate 20.

PRECAUTIONS

• Hematologic:
  • Thromboembolic complications may occur; increased risk with continuous infusion through central venous catheter; administer as a bolus infusion over several minutes.
• Immunologic:
  • Hypersensitivity reactions, including anaphylaxis, have been reported; increased risk with the presence of neutralizing antibodies to Factor IX; monitoring recommended; discontinue use if hypersensitivity occurs.
  • Neutralizing antibody formation has been reported; monitoring recommended.
• Renal:
  • Nephrotic syndrome has been reported following attempted immune tolerance induction in hemophilia B patients with Factor IX inhibitors and a history of allergic reactions to Factor IX.

ADVERSE EFFECTS

The most common adverse effects during clinical trials (n=153) were headache, oral paresthesia, and obstructive uropathy, reported in 1.3% each. Dizziness, dysgeusia, breath odor, fatigue, infusion site pain, palpitations, hematuria, renal colic, hypotension, and decreased appetite were reported in 0.7% each.

ADMINISTRATION

Allow vial and prefilled diluent syringe to reach room temperature. Using the vial adapter, slowly inject all the diluent provided into the drug vial and gently swirl until completely dissolved; do not shake vial. Then turn vial upside down and draw entire vial content into syringe. Following reconstitution, do not refrigerate, protect from direct sunlight, and use within 3 hours. The actual factor IX potency is stated on each vial, but the range is approximately 250, 500, 1000, 2000, 3000, or 4000 international units/vial. When reconstituted with the 5-mL syringe, the concentration will approximately range from 50 to 800 international units/mL. For IV use only. Administer as an IV bolus no faster than 10 mL per minute, according to patient comfort level. Do not administer in the same tubing or container with other drugs.

MONITORING

Monitor plasma factor IX activity, using a one-stage clotting assay, to confirm adequate factor IX levels have been achieved and maintained. The type of aPTT reagent used will affect the factor IX results. An underestimation of activity level will occur if a kaolin-based aPTT reagent is used in the one-stage clotting assay. Regularly monitor for the development of neutralizing antibodies (inhibitors) to factors IX using the Bethesda assay. Furthermore, monitor for antibodies if the expected factor IX activity levels in plasma are not attained or if bleeding is not controlled with the recommended dose. Closely observe for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of exposure to factor IX.