GALAFOLD

1 Dosing Considerations • Treatment with GALAFOLD should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of Fabry disease. GALAFOLD treatment is only indicated for adults and adolescents aged 12 years and older with Fabry disease who have an amenable GLA mutation that is interpreted by the specialist physician as causing Fabry disease (pathogenic, likely pathogenic) in the clinical context of the patient.

1 Mechanism of Action). 1 Mechanism of Action). Efficacy was not demonstrated in these patients. GALAFOLD may result in a net loss of α-Gal A activity in patients with non-amenable mutations, potentially worsening the disease condition.

• Clinical data supporting the effectiveness of GALAFOLD for the treatment of Fabry disease patients GALAFOLD® (migalastat capsules) Page 5 of 69 with amenable mutations are limited (see 14 CLINICAL TRIALS). In clinical trials, individual response to GALAFOLD treatment varied considerably among patients with amenable mutations.

Patients should be assessed for treatment response or failure when initiating GALAFOLD, and monitored periodically thereafter (every 6 months or more frequently) throughout the treatment (see 7 WARNINGS AND PRECAUTIONS - Monitoring and Laboratory Tests).

• GALAFOLD should not be used concomitantly with enzyme replacement therapy (see 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS). 2 Recommended Dose and Dosage Adjustment The recommended dosage regimen of GALAFOLD in patients ≥ 12 years and weighing ≥ 45 kg is 123 mg migalastat (1 capsule) taken once every other day at the same time of day.

2 Pharmacodynamics - Clinical Studies). 3 Special Populations and Conditions - Geriatrics). 3 Pharmacokinetics - Special Populations and Conditions - Renal Insufficiency). 3 Pharmacokinetics - Special Populations and Conditions - Hepatic Insufficiency).

3 Pharmacokinetics). Children < 12 years or adolescents weighing < 45 kg The safety and efficacy of GALAFOLD in children aged < 12 years or in adolescents weighing < 45 kg have not yet been established. No data are available in this age group.

4 Administration For oral use. 3 Pharmacokinetics – Absorption), therefore, it should be taken on an empty stomach. Food and caffeine should not be consumed for at least 2 hours before and 2 hours after taking GALAFOLD, to give a minimum of 4 hours fast.

1 Adverse Reaction Overview The most common adverse reaction reported from clinical trials of migalastat was headache, which was experienced by ≥ 10% of patients who received GALAFOLD. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.

The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.

The safety profile of GALAFOLD was assessed in two Phase 3 clinical trials: • A double-blind, randomized, placebo-controlled study in patients with Fabry disease and predicted to have migalastat-responsive GLA mutations (based on a preliminary in vitro assay) and who were naïve to enzyme replacement therapy (ERT-naïve trial) (Table 2) • A randomized, open-label study in patients with Fabry disease predicted to have migalastat- responsive GLA mutations and who were previously treated with enzyme replacement therapy (ERT-experienced trial) (Table 3).

8%) 0 †Once every other day ‡Percentages are calculated based on the total number of patients treated with the same dose/regimen. Patients who completed the 18-month treatment period in the ERT-experienced trial were eligible to receive treatment with GALAFOLD in an optional 12-month open-label extension period.

Eleven adverse drug reactions were newly reported between Month 18 and Month 30 of the study in the 51 patients who continued to receive GALAFOLD or switched from ERT to GALAFOLD during the 12-month open-label extension period: abdominal discomfort, feeling hot, hunger, migraine, muscle spasms, neuralgia, pain, proteinuria, tremor, vomiting, and vertigo; all reported in one patient (2%) except for muscle spasms which was reported in two patients (4%).

2 Study Results, Pediatric Population). < 12 years of age: GALAFOLD has not been authorized for use in pediatric patients less than 12 years of age. 2 Geriatrics > 65 years of age: Evidence from clinical studies and experience suggests that use in the geriatric population is not associated with differences in safety or effectiveness.

2 CONTRAINDICATIONS Migalastat is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

1 Dosing Considerations • Treatment with GALAFOLD should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of Fabry disease. GALAFOLD treatment is only indicated for adults and adolescents aged 12 years and older with Fabry disease who have an amenable GLA mutation that is interpreted by the specialist physician as causing Fabry disease (pathogenic, likely pathogenic) in the clinical context of the patient.

1 Mechanism of Action). 1 Mechanism of Action). Efficacy was not demonstrated in these patients. GALAFOLD may result in a net loss of α-Gal A activity in patients with non-amenable mutations, potentially worsening the disease condition.

• Clinical data supporting the effectiveness of GALAFOLD for the treatment of Fabry disease patients GALAFOLD® (migalastat capsules) Page 5 of 69 with amenable mutations are limited (see 14 CLINICAL TRIALS). In clinical trials, individual response to GALAFOLD treatment varied considerably among patients with amenable mutations.

Patients should be assessed for treatment response or failure when initiating GALAFOLD, and monitored periodically thereafter (every 6 months or more frequently) throughout the treatment (see 7 WARNINGS AND PRECAUTIONS - Monitoring and Laboratory Tests).

Migalastat is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.