KANUMA

2 Recommended Dose and Dosage Adjustment Patients with Rapidly Progressive LAL Deficiency Presenting within the First 6 Months of Life The recommended starting dose is 1 mg/kg or 3 mg/kg administered as an intravenous (IV) infusion once weekly (qw) , depending on the clinical status of the patient.

g. g. gastrointestinal symptoms): • a dose escalation to 3 mg/kg qw should be considered in case of suboptimal clinical response in KANUMA® (sebelipase alfa) Product Monograph Page 5 of 29 patients whose starting dose was 1 mg/kg qw; • a further dose escalation up to 5 mg/kg qw should be considered in case of suboptimal clinical response.

Further dose adjustments, as a reduction of the dose or an extension of the dose interval, can be made on an individual basis based on achievement and maintenance of therapeutic goals. 5 mg/kg once weekly. 5 mg/kg have not been studied.

Pediatric and Adult Patients with LAL Deficiency The recommended dose in children and adults who do not present with rapidly progressive LAL deficiency prior to 6 months of age is 1 mg/kg administered as an intravenous infusion once every other week (qow).

g. , gastrointestinal symptoms). 3 Reconstitution Dilution is required before use. • Each vial of Kanuma is intended for single use only. 9%) solution for infusion using aseptic technique. 2 μm filter. Preparation instructions Kanuma should be prepared and used according to the following steps: 1.

The number of vials to be diluted for infusion should be determined based on the patient’s weight and prescribed dose. 2. Round up to the next whole vial and remove the required number of vials from the refrigerator to allow them to reach room temperature.

3. It is recommended to allow Kanuma vials to reach a temperature between 15°C and 25°C to minimize the potential for the formation of sebelipase alfa protein particles in solution. 4. The vials should not be left outside the refrigerator longer than 24 hours prior to dilution for infusion.

The vials should not be frozen, heated or microwaved and should be protected from light. 5. The vials should not be shaken. Prior to dilution, the solution in the vials should be inspected visually; the solution should be clear to slightly opalescent, colourless to slightly coloured (yellow).

5 mg/kg once weekly (qw) in clinical studies (see Section 14 Clinical Trials). 5 month and 59 years old (70% were < 18 years old) at the time of first treatment with Kanuma and included 68 males and 57 females. In infants, the safety of Kanuma was evaluated in an open-label, single-arm, Phase 2/3 study (Study LAL CL03) and in an open-label, Phase 2 study (Study LAL-CL08).

8 years), the safety of Kanuma was evaluated in a randomised, placebo-controlled Phase 3 study (Study LAL CL02), an open-label, single-arm, Phase 2 study (LAL-CL01/LAL-CL04), and an open-label, single-arm, Phase 2 KANUMA® (sebelipase alfa) Product Monograph Page 10 of 29 study (LAL-CL06).

14 months). 7%). 35 mg/kg and 5 mg/kg once weekly. 19 months). The most serious adverse reactions experienced by 4% of patients in clinical trials were signs and symptoms consistent with anaphylaxis. Signs and symptoms included chest discomfort, conjunctival hyperemia, dyspnea, hyperemia, eyelid edema, severe respiratory distress, tachycardia, tachypnea, irritability, flushing, pruritus, urticaria, rhinorrhea, stridor, hypoxia, pallor and diarrhea.

2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. Tabulated list of adverse reactions Table 3 summarizes the most common adverse reactions occurring in 2 or more patients with rapidly progressive LAL deficiency presenting within the first 6 months of life receiving Kanuma.

Table 3:

Most Common Adverse Reactions in Infants with LAL Deficiency MedDRA System organ class MedDRA Preferred Term Kanuma N = 19 n (%) Immune system disorders Hypersensitivitya 13 (68) Anaphylactic reactionb 3 (16) Eye disorders Eyelid oedema 3 (16) Cardiac disorders Tachycardia 10 (53) Respiratory, thoracic and mediastinal disorders Respiratory distress 8 (42) Gastrointestinal disorders Diarrhea 15 (79) Vomiting 15 (79) Skin and subcutaneous tissue disorders Rash 7 (37) Rash maculo-papular 2 (11) General disorders and administration site conditions Hyperthermia 2 (11) Pyrexia 15 (79) Investigations Body temperature increased 4 (21) Oxygen saturation decreased 2 (11) Blood pressure increased 2 (11) KANUMA® (sebelipase alfa) Product Monograph Page 11 of 29 Heart rate increased 3 (16) Respiratory rate increased 4 (21) Drug specific antibody present 2 (11) aMay include: irritability, agitation, vomiting, urticaria, eczema, pruritus, pallor, and drug hypersensitivity bOccurred in 3 infant patients treated in clinical trials.

9%) solution for infusion. This should be taken into consideration when administering Kanuma to patients on a controlled sodium diet. Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Intravenous infusion Concentrate for Solution for Infusion 2 mg/mL Citric Acid Human serum albumin Trisodium citrate dehydrate Water for Injections KANUMA® (sebelipase alfa) Product Monograph Page 8 of 29 Hypersensitivity reactions, including anaphylactic reactions or anaphylaxis: • Hypersensitivity reactions, including anaphylactic reactions or anaphylaxis, have been reported in Kanuma-treated patients.

Anaphylaxis has occurred as early as the sixth infusion and as late as 1 year after treatment initiation. • Due to the potential for anaphylaxis, appropriate medical support should be readily available when Kanuma is administered. • Monitor patients closely during and after every infusion.

If anaphylaxis or a severe hypersensitivity reaction occurs, immediately discontinue the infusion and initiate appropriate medical treatment. • The majority of hypersensitivity reactions occurred during or within 4 hours of the completion of the infusion.

The management of hypersensitivity reactions should be based on the severity of the reactions and may include temporarily interrupting the infusion, lowering the infusion rate, and/or treatment with antihistamines, antipyretics, and/or corticosteroids.

• Pre-treatment with antipyretics and/or antihistamines may prevent subsequent reactions in those cases where symptomatic treatment was required. • The benefits and risks of re-administering Kanuma following a severe allergic reaction should be considered.

• Inform patients and/or caregivers of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur. Hypersensitivity to Eggs or Egg Products • Kanuma is produced in the egg whites of genetically engineered chickens.

Kanuma is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Section 6 Dosage Forms, Strengths, Composition and Packaging.