BRIEF SUMMARY

PEGUNIGALSADASE-alfa- (May 2023)

Indication-  To treat Febry disease        

Dosage-  Recommended dosage is 1 mg/kg every 2 weeks administered as an intravenous infusion

ADR- Most common adverse reactions (=15%) are: infusion-associated reactions, nasopharyngitis, headache, diarrhea, fatigue, nausea, back pain, pain in extremity, and sinusitis.

CI- None.

WARNINGS -

 • Infusion-Associated Reactions: If severe IARs occur, discontinue ELFABRIO and initiate appropriate medical treatment.

Pat inform- Advise the patient  that reactions related to the infusion may occur during and after treatment, including anaphyactic reactions, other serious or severe hypersensitivity reactions and  seek immediate medical care should these signs and symptoms occur.

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U.S.  APPROVED DRUGS DURING 2023                                        

Serial No 15

Name-        ELFABRIO

Acive  Ingredient -  Pegunigalsdase-alfa

 Pharmacological clssificiation-      To treat Febry disease                                                                                                                                                                                                                                                                                                                     

    Date of Approval-         5/9/2023 

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use ELFABRIO® safely and effectively.                                                                                                                       See full prescribing information for ELFABRIO. ELFABRIO (pegunigalsidase alfa-iwxj) injection, for intravenous use

Initial U.S. Approval: 2023

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS-                 See full prescribing information for complete boxed warning.

Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available.

If a severe hypersensitivity reaction occurs, discontinue ELFABRIO immediately and initiate appropriate medical treatment.

ADVERSE REACTIONS-

 Most common adverse reactions (=15%) are: infusion-associated reactions, nasopharyngitis, headache, diarrhea, fatigue, nausea, back pain, pain in extremity, and sinusitis.

CONTRAINDICATIONS-

 None.

WARNINGS AND PRECAUTIONS-

 • Infusion-Associated Reactions: If severe IARs occur, discontinue ELFABRIO and initiate appropriate medical treatment.

 • Membranoproliferative Glomerulonephritis: Monitor serum creatinine and urinary protein to creatinine ratio.                                                                                          Discontinue ELFABRIO if glomerulonephritis is suspected, until a diagnostic evaluation can be conducted. 

INDICATIONS AND USAGE-

 ELFABRIO is a hydrolytic lysosomal neutral glycosphingolipid-specific enzyme indicated for the treatment of adults with confirmed Fabry disease.

DOSAGE AND ADMINISTRATION-

 • For pretreatment recommendations, see Full Prescribing Information.

 • Recommended dosage is 1 mg/kg every 2 weeks administered as an intravenous infusion.

 • For dosage and administration modifications due to hypersensitivity reactions or infusion-associated reactions (IARs),see Full Prescribing Information.

 • For instructions on preparation (including dilution), storage, and administration (including rates for the initial 4-6 infusions for ERTexperienced and ERT-naïve patients), see Full Prescribing Information. 

DOSAGE FORMS AND STRENGTHS-

 Injection: 20 mg/10 mL (2 mg/mL) solution in a single-dose vial.

PATIENT COUNSELING INFORMATION-

Hypersensitivity Reactions Including Anaphylaxis and Infusion-Associated Reactions- (IARs)

Advise the patient and/or caregiver that reactions related to the infusion may occur during and after ELFABRIO treatment, including anaphylactic reactions, other serious or severe hypersensitivity reactions, and IARs.

Inform the patient and/or caregiver of the signs and symptoms of hypersensitivity reactions and IARs and to seek immediate medical care should these signs and symptoms occur.

Pregnancy-                                                                                                                         Safety Study-                                                                                                                  Advise a patient who is exposed to ELFABRIO during pregnancy that there is a  pregnancy safety study that monitors pregnancy outcomes.

Encourage the patient to report the pregnancy to Chiesi USA, Inc. at 1-888-661-9260 and https://chiesirarediseases.com/contact-us/medical-information-form [see Use in Specific Populations (8.1)].

Manufactured by: Chiesi Farmaceutici S.p.A. Via Palermo 26/A, 43122 Parma, Italy U.S. License No. 2245 Manufactured at: Chiesi Farmaceutici S.p.A. 43122 Parma, Italy Manufactured for: Chiesi USA, Inc. Cary NC, 27518, USA Product of Israel. ELFABRIO is a registered trademark of Chiesi Farmaceutici S.p.A. Licensed from Protalix Ltd. CTPA-001-0320-00-W

CLINICAL PHARMACOLOGY-

1. Mechanism of Action-                                                                                            Fabry disease is caused by deficiency of the lysosomal enzyme alpha-galactosidase A. ELFABRIO provides an exogenous source of alpha-galactosidase A. ELFABRIO is internalized and transported into lysosomes where it is thought to exert enzymatic activity and reduce accumulated globotriaosylceramide (Gb3).

2. Pharmacodynamics-                                                                                               Plasma globotriaosylsphingosine (lyso-Gb3, a metabolite of Gb3) concentrations are elevated in patients with Fabry disease. In patients with Fabry disease who were :

• ERT-naïve or had not received ERT treatment for at least 26 weeks and had a negative test for anti-pegunigalsidase alfa-iwxj antibodies (Trial 1),

3. Pharmacokinetics -                                                                                                   The pharmacokinetics (PK) of pegunigalsidase alfa-iwxj were evaluated in adult patients with Fabry disease and are presented as mean (standard deviation, SD) unless otherwise specified.

The pharmacokinetics of pegunigalsidase alfa-iwxj in plasma following intravenous infusion of ELFABRIO 1 mg/kg every 2 weeks in adult treatmentnaïve patients with

USE IN SPECIFIC POPULATIONS-

1. Pregnancy Risk Summary-                                                                                      There are no available data on ELFABRIO use in pregnant females to evaluate a drugassociated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes; however, as an enzyme replacement, ELFABRIO is not expected to cause adverse outcomes

The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes.

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.

2. Lactation Risk Summary-                                                                                         There are no data on the presence of pegunigalsidase alfa-iwxj in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ELFABRIO and any potential adverse effects on the breastfed infant from pegunigalsidase alfa-iwxj or from the underlying maternal condition. 

3.Pediatric Use-                                                                                                              The safety and effectiveness of ELFABRIO have not been established in pediatric patients.

4.Geriatric Use-                                                                                                          Clinical trials of ELFABRIO did not include patients 65 years of age and older to determine if they respond differently from younger adult patients.

5.Patients with Prior Enzyme Replacement Therapy-                                         Patients that received prior ERT are more likely to have pre-existing anti-drug antibodies (ADA) to pegunigalsidase alfa-iwxj which could be due to the ADA crossreactivity to pegunigalsidase alfa-iwxj by prior ERT.

When switching from other ERT to ELFABRIO:                                                             

• Pre-existing ADA may reduce the plasma pegunigalsidase alfa-iwxj concentrations, which may reduce ELFABRIO efficacy

. • The risk of ELFABRIO-related hypersensitivity and infusion-associated reactions may be increased in certain patients with pre-existing ADA from prior ERT.                . Consider monitoring clinical or pharmacodynamic responses (e.g., plasma lyso-Gb3 levels) when switching from agalsidase beta to ELFABRIO, in patients with pre-existing ADA.