Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

ELELYSO (BLA-022458)

(TALIGLUCERASE ALFA)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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12/22/2025 (SUPPL-34)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

Available data, including data from a product registry and pharmacovigilance reports, have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes in pregnant women exposed to ELELYSO. Additionally, there are risks associated with untreated symptomatic Type I Gaucher disease in pregnant women (see Clinical Considerations). In animal reproduction studies when pregnant rats and rabbits were administered taliglucerase alfa at intravenous doses up to 5 times the recommended human dose (RHD), there was no evidence of embryo-fetal toxicity (see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

. . .

8.2 Lactation

Additions and/or revisions underlined:

Risk Summary

There are no data on the presence of taliglucerase alfa in human milk or the effects of taliglucerase alfa on milk production. Lactation data from a product registry have not identified adverse reactions in infants exposed to taliglucerase alfa during breastfeeding. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ELELYSO and any potential adverse effects on the breastfed child from ELELYSO or from the underlying maternal condition.

01/17/2025 (SUPPL-33)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Hypersensitivity Reactions Including Anaphylaxis

Additions and/or revisions underlined:

…

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.

…

07/10/2024 (SUPPL-31)

Approved Drug Label (PDF)

Boxed Warning

Newly added section:

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS

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)].

5 Warnings and Precautions

5.1 Hypersensitivity Reactions Including Anaphylaxis

Additions and/or revisions underlined:

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):

…

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.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Hypersensitivity Reactions Including Anaphylaxis

Advise patients and caregivers that life-threatening hypersensitivity reactions, including anaphylaxis may occur with ELELYSO treatment.

Advise patients and caregivers that anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.

Inform patients and caregivers 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)].

05/09/2023 (SUPPL-30)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Hypersensitivity Reactions Including Anaphylaxis

Additions and/or revisions underlined:

Hypersensitivity reactions, including serious hypersensitivity reactions such as anaphylaxis, occurred in some ELELYSO-treated patients. 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 partients 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)]

Due to the potential for anaphylaxis, appropriate medical support should be readily available during the ELELYSO infusion. Observe patients closely for 3 hours after the start of the infusion. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur

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 severe hypersensitivity reactions including anaphylaxis occur, immediately stop the ELELYSO infusion and initiate appropriate treatment.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)].

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive additions and/or revisions, please refer to label.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

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), 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.

…

10/21/2019 (SUPPL-23)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Immunogenicity

(additions and/or revisions are underlined)

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other taliglucerase alfa products may be misleading.

…

Neutralizing Antibodies

Thirty (30) of the 31 adult and pediatric patients who developed ADA to ELELYSO during treatment or tested positive for ADA at baseline were evaluated for neutralizing activity of the ADA in the mannose receptor binding and enzyme activity assays. Nineteen (63%) of the 30 patients had neutralizing antibodies capable of inhibiting mannose receptor binding of ELELYSO. Eight of these 19 patients had neutralizing antibodies capable of inhibiting the enzymatic activity of ELELYSO. Available data do not indicate a clear relationship between the presence of mannose receptor binding neutralizing antibodies or neutralizing antibodies capable of inhibiting the enzymatic activity of ELELYSO and the therapeutic response to ELELYSO.

Other Antibodies

Nine (29%) of the 31 adult and pediatric patients who developed ADA to ELELYSO during treatment or tested positive for ADA at baseline also developed antibodies against plant-specific glycans in ELELYSO.

12/20/2016 (SUPPL-13)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Immunogenicity

(Additions and/or revisions are underlined)

Of the 2 patients who tested positive for ADA prior to initiation of ELELYSO treatment, one patient developed a hypersensitivity reaction during the first dose of ELELYSO and withdrew from the study. The second patient did not experience a hypersensitivity reaction.

Neutralizing antibodies were detected in 5 (17.2%) of 29 patients, 3 treatment-naïve adult patients, 1 treatment-naïve pediatric patient…

6.3 Postmarketing Experience

(Additions and/or revisions are underlined)

The following adverse reactions have been identified during post-approval use of ELELYSO in countries where it is marketed. Because these reactions include those reported voluntarily from a population of uncertain size in addition to those from postmarketing studies…

Gastrointestinal disorders: Vomiting, diarrhea

General disorders and administration site conditions: Fatigue

Immune system disorders: Anaphylaxis, Type III immune-mediated fixed drug eruption

Musculoskeletal and connective tissue disorders: Back pain

06/15/2016 (SUPPL-12)

Approved Drug Label (PDF)

6 Adverse Reactions

Immunogenicity

(updated paragraph) In a clinical trial of treatment-naïve pediatric patients, 2 (22%) of 9 patients developed ADA during treatment with ELELYSO, and one of 9 patients was ADA-positive prior to initiation of ELELYSO. Two of these 3 patients experienced hypersensitivity reactions (1 who developed ADA during treatment and became negative after Week 12 and 1 who was ADA-positive at baseline and became ADA negative after Week 8) and continued treatment with ELELYSO. The third patient who developed ADA during treatment and continued to be ADA-positive until study completion at Week 52 did not experience a hypersensitivity reaction.