These Highlights Do Not Include All The Information Needed To Use Elelyso Safely And Effectively. See Full Prescribing Information For Elelyso.

Treatment-Naïve Patients 4 Years of Age and Older

The recommended dosage of ELELYSO is 60 units/kg (based on actual body weight) administered every other week as a 60- to 120-minute intravenous infusion.

Refrigerate ELELYSO at 2 °C to 8 °C (36 °F to 46 °F) in the original carton to protect from light. Do not freeze.

Taliglucerase alfa is a hydrolytic lysosomal glucocerebroside-specific enzyme produced by recombinant DNA technology using plant cell culture (carrot). Taliglucerase alfa is a monomeric glycoprotein enzyme containing 4 N-linked glycosylation sites (kDa=60.8). Taliglucerase alfa differs from native human glucocerebrosidase by 2 amino acids at the N terminal and up to 7 amino acids at the C terminal. Taliglucerase alfa is a glycosylated protein with oligosaccharide chains at the glycosylation sites having terminal mannose sugars. These mannose-terminated oligosaccharide chains of taliglucerase alfa are specifically recognized by endocytic carbohydrate receptors on macrophages, the cells that accumulate lipid in Gaucher disease.

A unit is the amount of enzyme that catalyzes the hydrolysis of 1 micromole of the synthetic substrate para-nitrophenyl-β-D-glucopyranoside (pNP-Glc) per minute at 37 °C.

ELELYSO (taliglucerase alfa) for injection is supplied as a sterile, preservative-free, lyophilized powder for reconstitution and dilution prior to intravenous infusion. Each single-dose vial contains 200 units of taliglucerase alfa and D-mannitol (206.7 mg), polysorbate 80 (0.56 mg), and sodium citrate (30.4 mg). Citric acid may be added to adjust the pH at the time of manufacture. After reconstitution with 5.1 mL Sterile Water for Injection, USP, taliglucerase alfa concentration is 40 units/mL [see Dosage and Administration (2)]. Reconstituted solutions have a pH of approximately 6.0.

The safety and effectiveness of ELELYSO for the treatment of pediatric patients 4 years of age and older with a confirmed diagnosis of Type 1 Gaucher disease has been established. The use of ELELYSO for this indication is supported by evidence of effectiveness from adequate and well-controlled trials of ELELYSO in adults, with additional pharmacodynamic data from 5 pediatric patients and pharmacokinetic data from 9 pediatric patients who participated in clinical trials [see Clinical Studies (14.1, 14.2) and Clinical Pharmacology (12.3)]. Data from 14 pediatric patients were included in the safety evaluation [see Adverse Reactions (6.1)]. The safety and effectiveness of ELELYSO has not been established in patients less than 4 years of age.

Pediatric patients experienced a higher frequency of vomiting during ELELYSO treatment (4 of 9 treatment-naïve patients) than adult patients, and this may be a symptom of hypersensitivity reaction. The frequencies of other adverse reactions were similar between pediatric and adult patients treated with ELELYSO [see Adverse Reactions (6.1)].

During clinical trials, 8 patients aged 65 or older were treated with ELELYSO. Clinical trials of ELELYSO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

The observed incidence of ADA (including neutralizing antibodies [Nab]) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of ELELYSO or of other taliglucerase alfa products.

None.

The most common adverse reactions are:

• •
  Treatment-Naïve Adults (≥5%): headache, arthralgia, fatigue, nausea, dizziness, abdominal pain, pruritus, flushing, vomiting, urticaria (6.1).
• •
  Patients who Switched from Imiglucerase, after 9 Months on Treatment (≥10%): arthralgia, headache, pain in extremity (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Pharmacokinetics of taliglucerase alfa were evaluated in 38 patients (29 adult and 9 pediatric patients) who received intravenous infusions of ELELYSO 30 units/kg (50% of the recommended dosage) or 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] every other week. The pharmacokinetic parameters in adult and pediatric patients are summarized in Table 3.

In adult Type 1 Gaucher disease patients treated with ELELYSO 30 units/kg (50% of the recommended dosage) or 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] (N=29) every other week as initial therapy, pharmacokinetics were determined with the first dose and at Week 38 of treatment. The pharmacokinetics of taliglucerase alfa appeared to be nonlinear with a greater than dose-proportional increase in exposure at the doses studied.

No significant accumulation or change in taliglucerase alfa pharmacokinetics over time from Weeks 1 to 38 was observed with repeated dosages of 30 units/kg (50% of the recommended dosage) or 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] every other week. Based on the limited data, there were no significant pharmacokinetic differences between male and female patients in this study.

The pharmacokinetics of taliglucerase alfa were evaluated in 9 pediatric patients 4 to 17 years of age with Type 1 Gaucher disease who were treated with ELELYSO for 10 to 27 months. Six of the 9 patients were treatment-naïve, and 3 patients were switched from imiglucerase. In both the 30 units/kg (50% of the recommended dosage) and 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] dose groups, clearance values in pediatric patients were similar to those in adult patients. AUC values in pediatric patients were lower than AUC values in adult patients, due to weight-based dosing of taliglucerase alfa and lower body weights in pediatric patients.

ELELYSO is indicated for the treatment of patients 4 years of age and older with a confirmed diagnosis of Type 1 Gaucher disease.

Gaucher disease is an autosomal recessive disorder caused by mutations in the human glucocerebrosidase gene, which results in a reduced activity of the lysosomal enzyme glucocerebrosidase. Glucocerebrosidase catalyzes the conversion of the sphingolipid glucocerebroside into glucose and ceramide. The enzymatic deficiency results in accumulation of substrate glucocerebroside primarily in the lysosomal compartment of macrophages, giving rise to foam cells or "Gaucher cells," which accumulate in the liver, spleen and bone marrow.

ELELYSO, an enzyme replacement therapy, is a recombinant analog of human lysosomal glucocerebrosidase that catalyzes the hydrolysis of glucocerebroside to glucose and ceramide, reducing the amount of accumulated glucocerebroside. ELELYSO uptake into cellular lysosomes is mediated by binding of ELELYSO mannose oligosaccharide chains to specific mannose receptors on the cell surface leading to internalization and subsequent transport to the lysosomes.

See boxed warning (5.1)

Recommendations Prior to ELELYSO Treatment (2.1):

• •
  Administration of ELELYSO should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis.

Recommended Dosage in Patients 4 Years and Older (2.2):

• •
  Treatment-naïve: 60 units/kg administered every other week as a 60- to 120-minute intravenous infusion.
• •
  Patients switching from imiglucerase: Initiate ELELYSO intravenous treatment (60- to 120-minute infusion) with the same units/kg imiglucerase dosage and subsequently administer ELELYSO every other week. Dosage adjustments can be based on achievement and maintenance of each patient’s therapeutic goals.

Preparation and Administration (2.3, 2.4, 2.5):

• •
  Reconstitute, dilute and administer under the supervision of a healthcare professional.
• •
  See Full Prescribing Information for complete instructions. 

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

Prepare ELELYSO according to the following steps using aseptic technique:

• a.
  Determine the number of vials to be reconstituted based on the patient's weight in kg and the recommended dose [see Dosage and Administration (2.2)]. Round the number of vials up to the next whole number.
• 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, USP to yield a reconstituted product with a concentration of 40 units/mL and an extractable volume of 5 mL.
  • (1)
    Upon reconstitution, mix vials gently. DO NOT SHAKE.
  • (2)
    Prior to further dilution, visually inspect the reconstituted solution in the vials for particulate matter and discoloration. The solution should be clear and colorless. Discard if particulate matter is present or the solution is discolored.
• 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. Discard any unused reconstituted solution.
  • (1)
    For pediatric patients 4 years of age and older, use a final volume of 100 to 120 mL.
  • (2)
    For adult patients, may use a final volume of 130 to 150 mL. 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 the diluted solution gently. DO NOT SHAKE. Since this is a protein solution, slight flocculation (described as translucent fibers) occurs occasionally after dilution.
• f.
  Discard any unused diluted solution.

For injection: 200 units white to off-white lyophilized powder in a single-dose vial for reconstitution.

The following adverse reactions have been identified during post-approval use of ELELYSO. Because these reactions include those reported voluntarily from a population of uncertain size in addition to those from postmarketing studies, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

• •
  Gastrointestinal disorders: Vomiting, diarrhea
• •
  General disorders and administration site conditions: Fatigue
• •
  Immune system disorders: Anaphylaxis [see Warnings and Precautions (5.1)], Type III immune mediated fixed drug eruption
• •
  Musculoskeletal and connective tissue disorders: Back pain

After reconstitution and dilution, administer via intravenous infusion over a minimum of 60 minutes and with an in-line low protein-binding 0.2 micron filter.

• •
  For pediatric patients who weigh (based on actual body weight):
  • o
    Less than 30 kg use an infusion rate of 1 mL/minute.
  • o
    Greater than or equal to 30 kg, use an initial infusion rate of 1 mL/minute. After tolerability to ELELYSO is established, may increase the infusion rate to a maximum of 2 mL/minute.
• •
  For adult patients, use an initial infusion rate of 1.2 mL/minute. After tolerability to ELELYSO is established, may increase the infusion rate to a maximum of 2.2 mL/minute.

ELELYSO (taliglucerase alfa) for injection is supplied as a sterile, preservative-free, white to off-white lyophilized powder in a single-dose vial. Each vial of ELELYSO contains 200 units of taliglucerase alfa.

Each carton contains one vial (NDC 0069-0106-01).

NDC 0069-0106-01

Pfizer

Elelyso^®

(taliglucerase alfa)

for injection

200 units/vial

For intravenous infusion only

Single-Dose Vial. Discard

any unused portion.

Rx only

Administration of ELELYSO should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis [see Warnings and Precautions (5.1)].

Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1)].

To reduce the risk of hypersensitivity reactions, consider pretreatment with antihistamines and/or corticosteroids [see Warnings and Precautions (5.1)].

NDC 0069-0106-01

Pfizer

Elelyso^®

(taliglucerase alfa)

for injection

200 units/vial

For intravenous infusion only

ANTI- COUNTERFEIT

LABEL PLACEMENT

NO VARNISH

NO COPY

NO INK

Single-Dose Vial. Discard any

unused portion.

Rx only

Life‑threatening hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with enzyme replacement therapies, including ELELYSO. In clinical trials, (patients were not routinely pretreated with antihistamines and/or corticosteroids prior to ELELYSO infusions during the clinical trials):

• •
  2 of 72 (3%) ELELYSO-treated patients experienced signs and symptoms consistent with anaphylaxis including urticaria, hypotension, flushing, wheezing, chest tightness, nausea, vomiting, and dizziness. These reactions occurred during ELELYSO infusion.
• •
  21 of 72 (29%) ELELYSO-treated patients experienced hypersensitivity reactions, including the 2 ELELYSO‑treated patients who experienced signs and symptoms consistent with anaphylaxis. Signs and symptoms of these hypersensitivity reactions included pruritus, angioedema, flushing, erythema, rash, nausea, vomiting, cough, chest tightness, and throat irritation. These reactions occurred during ELELYSO infusion and up to 3 hours after the start of infusion [see Adverse Reactions (6.1)].

Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Administration of ELELYSO should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. Observe patients closely during and after the infusion.

ELELYSO-treated patients who developed anti-taliglucerase alfa antibodies (referred to as anti-drug antibodies (ADA)) generally had a greater frequency of hypersensitivity reactions compared to those who did not develop ADA [see Adverse Reactions (6.1)]. Closely monitor for hypersensitivity reactions in patients who develop ADA.

Management of hypersensitivity reactions should be based on the severity of the reaction and includes slowing or temporary interruption of the infusion and/or administration of antihistamines, antipyretics, and/or corticosteroids for mild reactions. To reduce the risk of hypersensitivity reactions, consider pretreatment with antihistamines and/or corticosteroids. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ELELYSO and immediately initiate appropriate medical treatment, including use of epinephrine.

Inform patients of the symptoms of life‑threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur.

Consider the risks and benefits of re-administering ELELYSO in patients who have experienced a severe hypersensitivity reaction associated with ELELYSO. Caution should be exercised upon rechallenge [see Adverse Reactions (6.2) ].

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).

Patients treated with enzyme replacement therapies have experienced life‑threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.

Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ELELYSO and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life‑threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1) ].

• •
  If the reconstituted ELELYSO vial is not used immediately, refrigerate at 2 °C to 8 °C (36 °F to 46 °F) for up to 24 hours (under protection from light) or store at controlled room temperature at 20 °C to 25 °C (68 °F to 77 °F) for up to 4 hours (without protection from light).
• •
  If the diluted solution is not administered immediately, refrigerate at 2 °C to 8 °C (36 °F to 46 °F) for up to 24 hours (under protection from light).
• •
  The total storage time for the reconstituted and diluted solution should not exceed 24 hours. Discard the unused reconstituted or diluted solution after 24 hours from the start of preparation.
• •
  Do not freeze.

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 (Trial 3). Trial 3 was a 9-month, multi-center, open-label, single arm study in patients who had been receiving intravenous 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 dosage of imiglucerase for at least 6 months prior to enrollment. 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 (9.5 units/kg to 60 units/kg given intravenously every other week). 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).

• •
  Eighteen of the 26 adult patients who completed the 9-month clinical trial continued treatment with ELELYSO (9.5 units/kg to 60 units/kg given intravenously every other week) in an open-label extension trial for additional 27 months (total duration of ELELYSO treatment was 36 months).
• •
  Five of the pediatric patients who completed the 9-month trial continued open-label treatment with ELELYSO (9.5 units/kg to 60 units/kg given intravenously every other week) for additional 24 months (total duration of ELELYSO treatment was 33 months).

Baseline Demographics

In Trial 3, patients were 6 to 66 years of age (mean age 42 years, including pediatric patients), 55% were male, 97% were White, and 16% and 84% were Hispanic/Latino and non Hispanic/Latino, respectively.

Efficacy Results

In Trial 3, 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. Mean (SD) organ volumes and hematologic values remained stable through 9 months of ELELYSO treatment. 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. The ELELYSO dosage 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.

During the 36‑month period, 18 ELELYSO-treated adult 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.

During the 33-month period, the 5 ELELYSO-treated pediatric patients demonstrated stability in these clinical parameters.

Treatment-Naïve Patients 4 Years of Age and Older

The recommended dosage of ELELYSO is 60 units/kg (based on actual body weight) administered every other week as a 60- to 120-minute intravenous infusion.

Refrigerate ELELYSO at 2 °C to 8 °C (36 °F to 46 °F) in the original carton to protect from light. Do not freeze.

Taliglucerase alfa is a hydrolytic lysosomal glucocerebroside-specific enzyme produced by recombinant DNA technology using plant cell culture (carrot). Taliglucerase alfa is a monomeric glycoprotein enzyme containing 4 N-linked glycosylation sites (kDa=60.8). Taliglucerase alfa differs from native human glucocerebrosidase by 2 amino acids at the N terminal and up to 7 amino acids at the C terminal. Taliglucerase alfa is a glycosylated protein with oligosaccharide chains at the glycosylation sites having terminal mannose sugars. These mannose-terminated oligosaccharide chains of taliglucerase alfa are specifically recognized by endocytic carbohydrate receptors on macrophages, the cells that accumulate lipid in Gaucher disease.

A unit is the amount of enzyme that catalyzes the hydrolysis of 1 micromole of the synthetic substrate para-nitrophenyl-β-D-glucopyranoside (pNP-Glc) per minute at 37 °C.

ELELYSO (taliglucerase alfa) for injection is supplied as a sterile, preservative-free, lyophilized powder for reconstitution and dilution prior to intravenous infusion. Each single-dose vial contains 200 units of taliglucerase alfa and D-mannitol (206.7 mg), polysorbate 80 (0.56 mg), and sodium citrate (30.4 mg). Citric acid may be added to adjust the pH at the time of manufacture. After reconstitution with 5.1 mL Sterile Water for Injection, USP, taliglucerase alfa concentration is 40 units/mL [see Dosage and Administration (2)]. Reconstituted solutions have a pH of approximately 6.0.

The safety and effectiveness of ELELYSO for the treatment of pediatric patients 4 years of age and older with a confirmed diagnosis of Type 1 Gaucher disease has been established. The use of ELELYSO for this indication is supported by evidence of effectiveness from adequate and well-controlled trials of ELELYSO in adults, with additional pharmacodynamic data from 5 pediatric patients and pharmacokinetic data from 9 pediatric patients who participated in clinical trials [see Clinical Studies (14.1, 14.2) and Clinical Pharmacology (12.3)]. Data from 14 pediatric patients were included in the safety evaluation [see Adverse Reactions (6.1)]. The safety and effectiveness of ELELYSO has not been established in patients less than 4 years of age.

Pediatric patients experienced a higher frequency of vomiting during ELELYSO treatment (4 of 9 treatment-naïve patients) than adult patients, and this may be a symptom of hypersensitivity reaction. The frequencies of other adverse reactions were similar between pediatric and adult patients treated with ELELYSO [see Adverse Reactions (6.1)].

During clinical trials, 8 patients aged 65 or older were treated with ELELYSO. Clinical trials of ELELYSO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

The observed incidence of ADA (including neutralizing antibodies [Nab]) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of ELELYSO or of other taliglucerase alfa products.

None.

The most common adverse reactions are:

• •
  Treatment-Naïve Adults (≥5%): headache, arthralgia, fatigue, nausea, dizziness, abdominal pain, pruritus, flushing, vomiting, urticaria (6.1).
• •
  Patients who Switched from Imiglucerase, after 9 Months on Treatment (≥10%): arthralgia, headache, pain in extremity (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Pharmacokinetics of taliglucerase alfa were evaluated in 38 patients (29 adult and 9 pediatric patients) who received intravenous infusions of ELELYSO 30 units/kg (50% of the recommended dosage) or 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] every other week. The pharmacokinetic parameters in adult and pediatric patients are summarized in Table 3.

In adult Type 1 Gaucher disease patients treated with ELELYSO 30 units/kg (50% of the recommended dosage) or 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] (N=29) every other week as initial therapy, pharmacokinetics were determined with the first dose and at Week 38 of treatment. The pharmacokinetics of taliglucerase alfa appeared to be nonlinear with a greater than dose-proportional increase in exposure at the doses studied.

No significant accumulation or change in taliglucerase alfa pharmacokinetics over time from Weeks 1 to 38 was observed with repeated dosages of 30 units/kg (50% of the recommended dosage) or 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] every other week. Based on the limited data, there were no significant pharmacokinetic differences between male and female patients in this study.

The pharmacokinetics of taliglucerase alfa were evaluated in 9 pediatric patients 4 to 17 years of age with Type 1 Gaucher disease who were treated with ELELYSO for 10 to 27 months. Six of the 9 patients were treatment-naïve, and 3 patients were switched from imiglucerase. In both the 30 units/kg (50% of the recommended dosage) and 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] dose groups, clearance values in pediatric patients were similar to those in adult patients. AUC values in pediatric patients were lower than AUC values in adult patients, due to weight-based dosing of taliglucerase alfa and lower body weights in pediatric patients.

ELELYSO is indicated for the treatment of patients 4 years of age and older with a confirmed diagnosis of Type 1 Gaucher disease.

Gaucher disease is an autosomal recessive disorder caused by mutations in the human glucocerebrosidase gene, which results in a reduced activity of the lysosomal enzyme glucocerebrosidase. Glucocerebrosidase catalyzes the conversion of the sphingolipid glucocerebroside into glucose and ceramide. The enzymatic deficiency results in accumulation of substrate glucocerebroside primarily in the lysosomal compartment of macrophages, giving rise to foam cells or "Gaucher cells," which accumulate in the liver, spleen and bone marrow.

ELELYSO, an enzyme replacement therapy, is a recombinant analog of human lysosomal glucocerebrosidase that catalyzes the hydrolysis of glucocerebroside to glucose and ceramide, reducing the amount of accumulated glucocerebroside. ELELYSO uptake into cellular lysosomes is mediated by binding of ELELYSO mannose oligosaccharide chains to specific mannose receptors on the cell surface leading to internalization and subsequent transport to the lysosomes.

See boxed warning (5.1)

Recommendations Prior to ELELYSO Treatment (2.1):

• •
  Administration of ELELYSO should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis.

Recommended Dosage in Patients 4 Years and Older (2.2):

• •
  Treatment-naïve: 60 units/kg administered every other week as a 60- to 120-minute intravenous infusion.
• •
  Patients switching from imiglucerase: Initiate ELELYSO intravenous treatment (60- to 120-minute infusion) with the same units/kg imiglucerase dosage and subsequently administer ELELYSO every other week. Dosage adjustments can be based on achievement and maintenance of each patient’s therapeutic goals.

Preparation and Administration (2.3, 2.4, 2.5):

• •
  Reconstitute, dilute and administer under the supervision of a healthcare professional.
• •
  See Full Prescribing Information for complete instructions. 

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

Prepare ELELYSO according to the following steps using aseptic technique:

• a.
  Determine the number of vials to be reconstituted based on the patient's weight in kg and the recommended dose [see Dosage and Administration (2.2)]. Round the number of vials up to the next whole number.
• 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, USP to yield a reconstituted product with a concentration of 40 units/mL and an extractable volume of 5 mL.
  • (1)
    Upon reconstitution, mix vials gently. DO NOT SHAKE.
  • (2)
    Prior to further dilution, visually inspect the reconstituted solution in the vials for particulate matter and discoloration. The solution should be clear and colorless. Discard if particulate matter is present or the solution is discolored.
• 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. Discard any unused reconstituted solution.
  • (1)
    For pediatric patients 4 years of age and older, use a final volume of 100 to 120 mL.
  • (2)
    For adult patients, may use a final volume of 130 to 150 mL. 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 the diluted solution gently. DO NOT SHAKE. Since this is a protein solution, slight flocculation (described as translucent fibers) occurs occasionally after dilution.
• f.
  Discard any unused diluted solution.

For injection: 200 units white to off-white lyophilized powder in a single-dose vial for reconstitution.

The following adverse reactions have been identified during post-approval use of ELELYSO. Because these reactions include those reported voluntarily from a population of uncertain size in addition to those from postmarketing studies, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

• •
  Gastrointestinal disorders: Vomiting, diarrhea
• •
  General disorders and administration site conditions: Fatigue
• •
  Immune system disorders: Anaphylaxis [see Warnings and Precautions (5.1)], Type III immune mediated fixed drug eruption
• •
  Musculoskeletal and connective tissue disorders: Back pain

After reconstitution and dilution, administer via intravenous infusion over a minimum of 60 minutes and with an in-line low protein-binding 0.2 micron filter.

• •
  For pediatric patients who weigh (based on actual body weight):
  • o
    Less than 30 kg use an infusion rate of 1 mL/minute.
  • o
    Greater than or equal to 30 kg, use an initial infusion rate of 1 mL/minute. After tolerability to ELELYSO is established, may increase the infusion rate to a maximum of 2 mL/minute.
• •
  For adult patients, use an initial infusion rate of 1.2 mL/minute. After tolerability to ELELYSO is established, may increase the infusion rate to a maximum of 2.2 mL/minute.

ELELYSO (taliglucerase alfa) for injection is supplied as a sterile, preservative-free, white to off-white lyophilized powder in a single-dose vial. Each vial of ELELYSO contains 200 units of taliglucerase alfa.

Each carton contains one vial (NDC 0069-0106-01).

NDC 0069-0106-01

Pfizer

Elelyso^®

(taliglucerase alfa)

for injection

200 units/vial

For intravenous infusion only

Single-Dose Vial. Discard

any unused portion.

Rx only

Administration of ELELYSO should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis [see Warnings and Precautions (5.1)].

Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1)].

To reduce the risk of hypersensitivity reactions, consider pretreatment with antihistamines and/or corticosteroids [see Warnings and Precautions (5.1)].

NDC 0069-0106-01

Pfizer

Elelyso^®

(taliglucerase alfa)

for injection

200 units/vial

For intravenous infusion only

ANTI- COUNTERFEIT

LABEL PLACEMENT

NO VARNISH

NO COPY

NO INK

Single-Dose Vial. Discard any

unused portion.

Rx only

Life‑threatening hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with enzyme replacement therapies, including ELELYSO. In clinical trials, (patients were not routinely pretreated with antihistamines and/or corticosteroids prior to ELELYSO infusions during the clinical trials):

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  2 of 72 (3%) ELELYSO-treated patients experienced signs and symptoms consistent with anaphylaxis including urticaria, hypotension, flushing, wheezing, chest tightness, nausea, vomiting, and dizziness. These reactions occurred during ELELYSO infusion.
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  21 of 72 (29%) ELELYSO-treated patients experienced hypersensitivity reactions, including the 2 ELELYSO‑treated patients who experienced signs and symptoms consistent with anaphylaxis. Signs and symptoms of these hypersensitivity reactions included pruritus, angioedema, flushing, erythema, rash, nausea, vomiting, cough, chest tightness, and throat irritation. These reactions occurred during ELELYSO infusion and up to 3 hours after the start of infusion [see Adverse Reactions (6.1)].

Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Administration of ELELYSO should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. Observe patients closely during and after the infusion.

ELELYSO-treated patients who developed anti-taliglucerase alfa antibodies (referred to as anti-drug antibodies (ADA)) generally had a greater frequency of hypersensitivity reactions compared to those who did not develop ADA [see Adverse Reactions (6.1)]. Closely monitor for hypersensitivity reactions in patients who develop ADA.

Management of hypersensitivity reactions should be based on the severity of the reaction and includes slowing or temporary interruption of the infusion and/or administration of antihistamines, antipyretics, and/or corticosteroids for mild reactions. To reduce the risk of hypersensitivity reactions, consider pretreatment with antihistamines and/or corticosteroids. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ELELYSO and immediately initiate appropriate medical treatment, including use of epinephrine.

Inform patients of the symptoms of life‑threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur.

Consider the risks and benefits of re-administering ELELYSO in patients who have experienced a severe hypersensitivity reaction associated with ELELYSO. Caution should be exercised upon rechallenge [see Adverse Reactions (6.2) ].

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).

Patients treated with enzyme replacement therapies have experienced life‑threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.

Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ELELYSO and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life‑threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1) ].

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  If the reconstituted ELELYSO vial is not used immediately, refrigerate at 2 °C to 8 °C (36 °F to 46 °F) for up to 24 hours (under protection from light) or store at controlled room temperature at 20 °C to 25 °C (68 °F to 77 °F) for up to 4 hours (without protection from light).
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  If the diluted solution is not administered immediately, refrigerate at 2 °C to 8 °C (36 °F to 46 °F) for up to 24 hours (under protection from light).
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  The total storage time for the reconstituted and diluted solution should not exceed 24 hours. Discard the unused reconstituted or diluted solution after 24 hours from the start of preparation.
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  Do not freeze.

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 (Trial 3). Trial 3 was a 9-month, multi-center, open-label, single arm study in patients who had been receiving intravenous 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 dosage of imiglucerase for at least 6 months prior to enrollment. 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 (9.5 units/kg to 60 units/kg given intravenously every other week). 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).

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  Eighteen of the 26 adult patients who completed the 9-month clinical trial continued treatment with ELELYSO (9.5 units/kg to 60 units/kg given intravenously every other week) in an open-label extension trial for additional 27 months (total duration of ELELYSO treatment was 36 months).
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  Five of the pediatric patients who completed the 9-month trial continued open-label treatment with ELELYSO (9.5 units/kg to 60 units/kg given intravenously every other week) for additional 24 months (total duration of ELELYSO treatment was 33 months).

Baseline Demographics

In Trial 3, patients were 6 to 66 years of age (mean age 42 years, including pediatric patients), 55% were male, 97% were White, and 16% and 84% were Hispanic/Latino and non Hispanic/Latino, respectively.

Efficacy Results

In Trial 3, 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. Mean (SD) organ volumes and hematologic values remained stable through 9 months of ELELYSO treatment. 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. The ELELYSO dosage 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.

During the 36‑month period, 18 ELELYSO-treated adult 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.

During the 33-month period, the 5 ELELYSO-treated pediatric patients demonstrated stability in these clinical parameters.