Elfabrio Drug Information

ELFABRIO is indicated for the treatment of adults with confirmed Fabry disease.

Storage of the Diluted Solution If the diluted

• ELFABRIO solution is not used immediately: ○ Refrigerate the diluted solution at 2°C to 8°C (36°F to 46°F) for up to 24 hours. The solution must be infused within 8 hours after removal from the refrigerator, inclusive of the total infusion time, or discarded. ○ Store the diluted solution at room temperature at 20°C to 25°C (68°F to 77°F) for up to 8 hours. Do not freeze or shake. 2. 6 Administration Instructions Administer ELFABRIO as follows: Use an in-line low protein-binding, 0.2 micron, in-line filter during administration. For the initial 4-6 infusions, infuse ELFABRIO using the infusion rates described in Table 1 for ERT-experienced patients and Table 2 for ERT-naïve patients. If a patient tolerates the initial 4-6 ELFABRIO infusions, the duration of every third infusion may be decreased in decrements of 30 minutes as tolerated. The minimum recommended infusion duration is 1.5 hours. At the end of the infusion, flush the line with 0.9% Sodium Chloride Injection using the same infusion rate as the one used for the last part of the ELFABRIO infusion. Do not infuse ELFABRIO in the same intravenous line with other products. Table 1 presents the recommended infusion rates for the initial 4-6 ELFABRIO infusions based on actual body weight for ERT-experienced patients. Infusion rate may be slowed in case of a hypersensitivity reaction or an IAR. Administration of ELFABRIO to Patients Previously Treated with ERT w ith an Infusion Duration Over 3 Hours In patients previously treated with an ERT with an infusion duration over 3 hours: Use the same infusion rate for the ELFABRIO infusion. Home Infusion Home administration under the supervision of a healthcare provider may be considered for patients who have reached an infusion duration that is tolerated well. The decision to have a patient move to home infusion should be made after evaluation and recommendation by a healthcare provider. The infusion duration should remain constant for home administration and the duration should only be decreased in a healthcare facility. In case of a missed dose or delayed infusion, a healthcare provider should be contacted.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in clinical practice. Patients received 1 mg/kg of ELFABRIO given intravenously every 2 weeks for at least 104 weeks. One ELFABRIO-treated patient experienced a severe hypersensitivity reaction during the first infusion.

The patient withdrew from the trial following a moderate hypersensitivity reaction during the second infusion. Table 3 lists adverse reactions reported in at least 5% of ELFABRIO-treated patients in Trial 2. Table 3: Adverse Reactions in Adults With Fabry Disease Trial Adverse reactions were those that occurred in ≥ 5% of ELFABRIO-treated patients. 2 “Infusion-associated reaction” includes nausea, vomiting, abdominal pain, diarrhea, fatigue, chills, malaise, non-cardiac chest pain, hypersensitivity, body temperature increased, burning sensation, neuralgia, agitation, throat irritation, pruritic rash, and flushing.

Events occurring within 24 hours. 3 “Hypersensitivity” includes macular rash, pruritic rash, and face swelling. Events occurring within 24 hours. 4 The events of hypersensitivity and pruritic rash fall in both hypersensitivity and IAR categories. Membranoproliferative Glomerulonephritis A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported in an ELFABRIO-treated patient.

Immunogenicity: Anti - D rug Antibody-Associated Adverse Reactions Of the patients who experienced serious hypersensitivity reactions during the first ELFABRIO infusion and had pre-infusion samples and samples available for testing at the time of the event, all but one had pre-existing IgE ADAs and all tested positive for IgE ADAs at the time of the reaction.

Pregnancy Risk Summary There are no available data on ELFABRIO use in pregnant females to evaluate a drug-associated 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. Animal reproduction studies have been conducted with pegunigalsidase alfa-iwxj in pregnant rats and rabbits. No adverse effects on embryofetal development were observed in pregnant rats intravenously administered pegunigalsidase alfa-iwxj twice per week at exposures up to 3.6 times that of the maximum recommended human dose (MRHD) (based on area under the concentration-time curve (AUC)).

Maternal toxicity was observed in pregnant rabbits intravenously administered pegunigalsidase alfa-iwxj twice per week at doses that were ≥ 3.2 times the MRHD (based on human equivalent dose). 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 respectively. There is a pregnancy safety study for ELFABRIO. If a patient becomes pregnant while receiving ELFABRIO, healthcare providers should report ELFABRIO exposure by calling 1-888-661-9260 or visiting https://chiesirarediseases.com/contact-us/medical-information-form.

Data Animal Data In an embryofetal development study in the rat, pegunigalsidase alfa-iwxj was administered during the period of organogenesis on gestation day No maternal or fetal adverse effects were noted at exposures that were up to 3.6-fold greater than the recommended dose of 1 mg/kg every two weeks. In an embryofetal development study in the rabbit, administration of pegunigalsidase alfa-iwxj during the period of organogenesis on gestation day resulted in maternal toxicity, including maternal mortality, decreased body weight, and decreased feed consumption. These effects were observed at exposures that were ≥ 3.2-fold greater than the recommended dose of 1 mg/kg every two weeks.

Adverse embryofetal effects included abortion, increased late resorptions, number of does with resorptions, and increased post-implantation loss at exposures that were 6.5 fold greater than the recommended dose of 1 mg/kg every two weeks. Decreased fetal body weight was observed at exposures that were ≥ 3.2 times greater than the recommended dose of 1 mg/kg every two weeks. There was no increase in fetal external, skeletal, or visceral malformations.

8. 4 Pediatric Use The safety and effectiveness of ELFABRIO have not been established in pediatric patients.