Elelyso Injection

Name: Elelyso Injection

Elelyso Injection Dosage and Administration

Recommended Dosage in Patients 4 Years and Older

Treatment-naïve patients: The recommended dosage of ELELYSO for long-term treatment is 60 units/kg of body weight administered every other week as a 60 to 120 minute intravenous infusion.

Patients switching from imiglucerase: Patients currently being treated with imiglucerase for Type 1 Gaucher disease can be switched to ELELYSO. Patients previously treated on a stable dosage of imiglucerase are recommended to begin treatment with ELELYSO at that same units/kg dosage when they switch from imiglucerase to ELELYSO. Administer ELELYSO for long-term treatment every other week as a 60 to 120 minute intravenous infusion. Dosage adjustments can be made based on achievement and maintenance of each patient's therapeutic goals [see Clinical Studies (14.2)].

Preparation Instructions

ELELYSO should be reconstituted, diluted, and administered under the supervision of a healthcare professional.

Each vial of ELELYSO provides 200 units of taliglucerase alfa and is intended for single use only. Do not use the vial more than one time. The reconstitution and dilution steps must be completed using aseptic technique.

ELELYSO should be reconstituted with Sterile Water for Injection and diluted with 0.9% Sodium Chloride Injection, USP, to a final volume of 100 mL to 200 mL, and delivered by intravenous infusion.

Prepare ELELYSO according to the following steps. Use aseptic technique.

a. Determine the number of vials to be reconstituted based on the patient's weight and the recommended dose of 60 units/kg, using the following calculations (1–3): (1) Total dose in units = Patient's weight (kg) × dose (units/kg) (2) Total number of vials = Total dose in units divided by 200 units/vial (3) Round up to the next whole vial. b. Remove the required number of vials from the refrigerator. Do not leave these vials at room temperature longer than 24 hours prior to reconstitution. Do not heat or microwave these vials. c. Reconstitute each vial of ELELYSO with 5.1 mL of Sterile Water for Injection to yield a reconstituted product with a concentration of 40 units/mL and an extractable volume of 5 mL. Upon reconstitution, mix vials gently. DO NOT SHAKE. Prior to further dilution, visually inspect the solution in the vials; the solution should be clear and colorless. Do not use if the solution is discolored or if foreign particulate matter is present. d. Withdraw the calculated dose of drug from the appropriate number of vials and dilute with 0.9% Sodium Chloride Injection, USP, to a final volume of 100 to 200 mL. i. For pediatric patients, a final volume of 100 to 120 mL should be used. ii. For adult patients, a final volume of 130 to 150 mL may be used. However, if the volume of reconstituted product alone is equal to or greater than 130 to 150 mL, then the final volume should not exceed 200 mL. e. Mix gently. DO NOT SHAKE. Since this is a protein solution, slight flocculation (described as translucent fibers) occurs occasionally after dilution.

Administration Instructions

After reconstitution and dilution, the preparation should be administered via intravenous infusion and filtered through an in-line low protein-binding 0.2 μm filter.

  • For pediatric patients: An initial infusion rate of 1 mL/minute should be used. After tolerability to ELELYSO is established, the infusion rate may be increased, but should not exceed the maximum recommended infusion rate of 2 mL/minute. The total volume of the infusion should be delivered over a minimum of 60 minutes.
  • For adult patients: An initial infusion rate of 1.2 mL/minute should be used. After tolerability to ELELYSO is established, the infusion rate may be increased, but should not exceed the maximum recommended infusion rate of 2.2 mL/minute. The total volume of the infusion should be delivered over a minimum of 60 minutes.

As ELELYSO contains no preservative, the product should be used immediately once reconstituted. If immediate use is not possible, the reconstituted product may be stored for up to 24 hours at 2 to 8 °C (36 to 46 °F) under protection from light or up to 4 hours at 20 to 25 °C (68 to 77 °F) without protection from light. The diluted product may be stored for up to 24 hours at 2 to 8 °C (36 to 46 °F) under protection from light. Storage of the reconstituted product and the diluted product should not exceed a total of 24 hours. Do not freeze. Discard any unused product.

Warnings and Precautions

Hypersensitivity Reactions Including Anaphylaxis

Serious hypersensitivity reactions, including anaphylaxis, have occurred in some patients treated with ELELYSO. In clinical trials, 2 of 72 (3%) patients treated with ELELYSO experienced signs and symptoms consistent with anaphylaxis. Signs and symptoms of these patients included urticaria, hypotension, flushing, wheezing, chest tightness, nausea, vomiting, and dizziness. These reactions occurred during ELELYSO infusion.

In clinical trials with ELELYSO, 21 of 72 (29%) patients experienced hypersensitivity reactions, including anaphylaxis. Signs and symptoms of hypersensitivity reactions included pruritus, angioedema, flushing, erythema, rash, nausea, vomiting, cough, chest tightness, and throat irritation. These reactions have occurred up to 3 hours after the start of infusion [see Adverse Reactions (6.1)].

Due to the potential for anaphylaxis, appropriate medical support should be readily available when ELELYSO is administered. Observe patients closely for an appropriate period of time after administration of ELELYSO, taking into account the time to onset of anaphylaxis seen in clinical trials. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur. If anaphylaxis occurs, ELELYSO should be immediately discontinued, and appropriate medical treatment should be initiated.

Management of hypersensitivity reactions should be based on the severity of the reaction and include slowing or temporary interruption of the infusion and/or administration of antihistamines, antipyretics, and/or corticosteroids for mild reactions. Pretreatment with antihistamines and/or corticosteroids may prevent subsequent hypersensitivity reactions. Patients were not routinely premedicated prior to infusion of ELELYSO during clinical studies. If severe hypersensitivity reactions occur, immediately stop the infusion of ELELYSO and initiate appropriate treatment.

Consider the risks and benefits of re-administering ELELYSO in patients who have experienced a severe reaction associated with ELELYSO. Caution should be exercised upon rechallenge, and appropriate medical support should be readily available [see Adverse Reactions (6.3)].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate carcinogenic potential or studies to evaluate mutagenic potential have not been performed with taliglucerase alfa. In a male and female fertility study in rats, taliglucerase alfa did not cause any significant adverse effect on male or female fertility parameters up to a maximum dose of 55 mg/kg/day (about 5 times the recommended human dose of 60 units/kg based on the body surface area).

Clinical Studies

Clinical Trials of ELELYSO as Initial Therapy

Clinical Trial in Patients 19 Years and Older

The safety and efficacy of ELELYSO were assessed in 31 adult patients with Type 1 Gaucher disease. The trial was a 9-month, multi-center, double-blind, randomized trial in patients with Gaucher disease-related enlarged spleens (>8 times normal) and thrombocytopenia (<120,000 /mm3). Sixteen patients had enlarged livers and ten patients had anemia at baseline. All patients were naïve to ERT. Patients with severe neurological symptoms were excluded from the trial. Patients were 19 to 74 years of age (mean age 36 years), and 48% were male. Patients were randomized to receive ELELYSO at a dosage of either 30 units/kg (n=15) or 60 units/kg (n=16) every other week. The recommended dosage in treatment-naïve adult patients is 60 units/kg every other week. ELELYSO 30 units/kg every other week is not a recommended dosage [see Dosage and Administration (2.1)].

Table 4 shows the baseline values and mean (SD) changes in clinical parameters (spleen volume, liver volume, platelet count, and hemoglobin) after 9 months of treatment with ELELYSO. For all clinical trials, liver and spleen volumes were measured by MRI and are reported as percentage of body weight (%BW) and multiples of normal (MN). The observed change from baseline in the primary endpoint, reduction in spleen volume, was considered to be clinically meaningful in light of the natural history of untreated Gaucher disease.

Table 4: Mean (SD*) Changes in Clinical Parameters from Baseline to 9 Months in Treatment-Naïve Adults with Type 1 Gaucher Disease Initiating Therapy with ELELYSO (N=31)
Clinical Parameter 30 units/kg† (n=15)
Mean (SD)
60 units/kg (n=16)
Mean (SD)
* SD = standard deviation † The recommended ELELYSO dosage in treatment-naïve adult patients is 60 units/kg every other week. ELELYSO 30 units/kg every other week is not a recommended dosage. [see Dosage and Administration (2.1)] ‡ %BW = percentage of body weight § MN = multiples of normal
Spleen Volume (%BW‡) Baseline 3.1 (1.5) 3.3 (2.7)
Month 9 2.2 (1.3) 2.1 (1.9)
Change -0.9 (0.4) -1.3 (1.1)
Spleen Volume (MN§) Baseline 15.4 (7.7) 16.7 (13.4)
Month 9 11.1 (6.3) 10.4 (9.4)
Change -4.5 (2.1) -6.6 (5.4)
Liver Volume (%BW) Baseline 4.2 (0.9) 3.8 (1.0)
Month 9 3.6 (0.7) 3.1 (0.7)
Change -0.6 (0.5) -0.6 (0.4)
Liver Volume (MN) Baseline 1.7 (0.4) 1.5 (0.4)
Month 9 1.4 (0.3) 1.2 (0.3)
Change -0.2 (0.2) -0.3 (0.2)
Platelet Count (mm3) Baseline 75,320 (40,861) 65,038 (28,668)
Month 9 86,747 (50,989) 106,531 (53,212)
Change 11,427 (20,214) 41,494 (47,063)
Hemoglobin (g/dl) Baseline 12.2 (1.7) 11.4 (2.6)
Month 9 14.0 (1.4) 13.6 (2.0)
Change 1.6 (1.4) 2.2 (1.4)

Twenty-six of the 31 patients in this 9-month clinical trial continued blinded treatment with ELELYSO in an extension trial for a total treatment duration of 24 months. The following data are the changes in clinical parameters from baseline to Month 24 for the 30 units/kg (n=12) and 60 units/kg (n=14) dose groups, respectively: mean (SD) spleen volume (%BW) decreased by 1.4 (0.6) and 2.0 (2.0), in MN by 6.8 (3.0) and 10.2 (9.8); hemoglobin increased by 1.3 (1.7) g/dL and 2.4 (2.3) g/dL; liver volume (%BW) decreased by 1.1 (0.5) and 1.0 (0.7), in MN by 0.4 (0.2) and 0.4 (0.3 and platelet count increased 28,433 (31,996) /mm3 and 72,029 (68,157) /mm3. Twenty-three of the 26 patients who continued open-label treatment with ELELYSO for additional 12 months demonstrated stability in these clinical parameters.

Clinical Trial in Patients 16 years and Younger

The safety and efficacy of ELELYSO were assessed in 9 pediatric patients with Type 1 Gaucher disease. The trial was a 12-month, multi-center, double-blind, randomized study in treatment-naïve patients. Patients were 2 to 13 years of age (mean age 8.1 years), and 67% were male. Patients were randomized to receive ELELYSO at a dosage of either 30 units/kg (n=4) or 60 units/kg (n=5) every other week. The recommended ELELYSO dosage in treatment-naïve pediatric patients is 60 units/kg every other week. ELELYSO 30 units/kg every other week is not a recommended dosage [see Dosage and Administration (2.1)].

The following data are the changes [median (Q1, Q3)] in clinical parameters from baseline to Month 12 for the 60 units/kg dose group (n=5): spleen volume decreased from 18.4 (14.2, 35.1) MN to 11.0 (8.3, 14.5) MN; hemoglobin increased from 11.1 (9.2, 11.3) g/dL to 11.7 (11.5, 12.9) g/dL; liver volume decreased from 2.1 (2.0, 2.3) MN to 1.6 (1.5, 1.9) MN; platelet count increased from 80,000 (79,000, 87,000)/mm3 to 131,000 (119,000, 215,000)/mm3.

Nine pediatric patients in the 12-month clinical trial continued blinded treatment with ELELYSO in an extension trial for a total treatment duration of 24 months. The following data are the changes [median (Q1, Q3)] in clinical parameters from baseline to Month 24 for the 60 units/kg dose group (n=5): spleen volume decreased by 19.0 (8.3, 41.2) MN; hemoglobin increased by 2.5 (1.9, 3.0) g/dL; liver volume decreased by 0.8 (0.6, 1.1) MN; and platelet count increased by 76,000 (67,000, 100,000)/mm3.

Clinical Trial in Patients Switching from Imiglucerase Treatment to ELELYSO

The safety and efficacy of ELELYSO were assessed in 31 patients (26 adult and 5 pediatric patients) with Type 1 Gaucher disease who were switched from imiglucerase to ELELYSO. The trial was a 9-month, multi-center, open-label, single arm study in patients who had been receiving treatment with imiglucerase at dosages ranging from 9.5 units/kg to 60 units/kg every other week for a minimum of 2 years. Patients were required to be clinically stable and have a stable biweekly dose of imiglucerase for at least 6 months prior to enrollment. Patients were 6 to 66 years of age (mean age 42 years, including pediatric patients), and 55% were male. Imiglucerase therapy was stopped, and treatment with ELELYSO was administered every other week at the same number of units as each patient's previous imiglucerase dose. If needed, adjustment of dosage was allowed during the study in order to maintain stability of clinical parameters (i.e., spleen volume, liver volume, platelet count, and hemoglobin).

Mean (SD) organ volumes and hematologic values remained stable through 9 months of ELELYSO treatment. At baseline, spleen volume was 5.2 (4.5) MN, liver volume was 1.0 (0.3) MN, platelet count was 161,137 (73,387)/mm3, and hemoglobin was 13.5 (1.4) g/dL. After 9 months of ELELYSO treatment, spleen volume was 4.8 (4.6) MN, liver volume was 1.0 (0.2) MN, platelet count was 161,167 (80,820)/mm3, and hemoglobin was 13.4 (1.5) g/dL. ELELYSO dose remained unchanged in 30 of 31 patients. One patient required a dose increase at Week 24 (from 9.5 units/kg to 19 units/kg) for a platelet count of 92,000/mm3 at Week 22, which subsequently increased to 170,000/mm3 at Month 9.

Eighteen of the 26 adult patients who completed the 9-month clinical trial continued treatment with ELELYSO in an open-label extension trial for additional 27 months (total treatment 36 months). Patients maintained stability in clinical parameters (spleen volume, liver volume, platelet count and hemoglobin); however only 10 of 18 adult patients completed 27 months of ELELYSO treatment in the extension trial and only 7 patients had their spleen and liver volumes assessed at 36 months.

Five pediatric patients in the 9-month clinical trial who continued open-label treatment with ELELYSO for additional 24 months demonstrated stability in these clinical parameters.

PRINCIPAL DISPLAY PANEL - 200 Unit Vial Label

NDC 0069-0106-01

Pfizer

Elelyso®
(taliglucerase alfa)
for injection

200 units/vial

For intravenous infusion only

Single-use vial. Discard any
unused portion.
Rx only

For Healthcare Professionals

Applies to taliglucerase alfa: intravenous powder for injection

General

The most frequently reported side effects were headache, arthralgia, pain in extremity, fatigue, nausea, dizziness, pruritus, flushing, abdominal pain, vomiting, back pain, and rash.[Ref]

Gastrointestinal

Very common (10% or more): Vomiting, abdominal pain
Common (1% to 10%): Nausea, diarrhea
Frequency not reported: Gastrointestinal inflammation[Ref]

Hypersensitivity

In clinical trials, hypersensitivity reactions (including anaphylaxis) were reported in 29% of patients; these reactions occurred up to 3 hours after the start of infusion. Serious hypersensitivity reactions (including anaphylaxis) were reported in some patients. In clinical trials, 3% of patients had signs/symptoms consistent with anaphylaxis; these reactions occurred during the infusion.[Ref]

Very common (10% or more): Hypersensitivity reactions (including anaphylaxis; 29%)
Frequency not reported: Type III immune-mediated fixed drug eruption
Postmarketing reports: Anaphylaxis[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia (up to 13%), pain in extremity (up to 10%)
Common (1% to 10%): Back pain, bone pain
Frequency not reported: Muscle spasms[Ref]

Immunologic

Very common (10% or more): Development of anti-drug antibodies (up to 53%), neutralizing antibodies detected (10.3%)[Ref]

Nervous system

Very common (10% or more): Headache (up to 19%)
Common (1% to 10%): Dizziness, paresthesia
Frequency not reported: Tremor[Ref]

Other

Common (1% to 10%): Fatigue, flushing, peripheral edema, infusion reaction, weight increased
Frequency not reported: Chest discomfort, feeling hot[Ref]

Infusion-related reactions occurred most often within 24 hours of the infusion and consisted of arthralgia, headache, vomiting, flushing, pruritus, pain in extremity, pulmonary hypertension, diarrhea, chest discomfort, feeling hot, muscle spasms, tremor, throat irritation, erythema, and rash.[Ref]

Dermatologic

Common (1% to 10%): Pruritus, erythema, rash, urticaria[Ref]

Respiratory

Common (1% to 10%): Throat irritation, rhinorrhea, sneezing
Frequency not reported: Pulmonary hypertension[Ref]

Hepatic

Common (1%to 10%): ALT increased[Ref]

Local

Common (1% to 10%): Infusion site pain[Ref]

Ocular

Common (1% to 10%): Eye pruritus, eye swelling, lacrimation increased[Ref]

Some side effects of taliglucerase alfa may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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