Galafold™ (Migalastat Hydrochloride) Capsule / Drug/Drug Class: Agents for Fabry Disease Prepared For: MO Healthnet Prepared By: Conduent

Drug Monograph

Galafold™ (migalastat hydrochloride) capsule / Drug/Drug Class: Agents for Fabry Disease Prepared for: MO HealthNet Prepared by: Conduent

New Criteria Revision of Existing Criteria

Executive Summary

The purpose of this monograph is to provide a review of new therapy to determine whether the reviewed drug should be made available on an open Purpose: access basis to prescribers, require a clinical edit or require prior authorization for use.

Galafold™ is available in a capsule containing 123 mg of migalastat. Dosage Forms & Manufacturer: Manufactured for: Amicus Therapeutics U.S., Inc., Cranbury, NJ 08512

The clinical trials of Galafold™ included one randomized, double-blind, placebo-controlled clinical trial of 6 months duration followed by a 6-month open-label treatment phase. A second trial was a randomized, open-label, active-controlled clinical trial of 18 months duration in patients with Fabry disease receiving enzyme replacement therapy who were randomized to either switch to Galafold™ or continue enzyme replacement therapy (ERT). Summary of In the first trial, at 6 months, patients treated with Galafold™ had lower Findings: plasma GL-3 levels and greater reduction in the mean number of GL-3 inclusions per kidney interstitial capillary, compared with those treated with placebo. In the second trial, Galafold™ and ERT had comparable effects on renal function in patients with amenable mutations. Left ventricular mass index decreased significantly from baseline to month 18 in Galafold™ patients whereas a smaller non-significant change was observed in patients remaining on ERT

Status Prior Authorization (PA) Required Open Access Recommendation: Clinical Edit PDL

Type of PA Increased Risk of ADE Non-Preferred Agent Criteria: Appropriate Indications No PA Required

Purpose The purpose of this monograph is to provide a review of new therapy to determine whether the reviewed drug should be considered a prior authorization drug, a clinical edit drug or an open access drug. While prescription expenditures are increasing at double-digit rates, payers are evaluating ways to control these costs by influencing prescriber behavior and guide appropriate medication usage. This review will assist in the achievement of qualitative and economic goals related to health care resource utilization. Restricting the use of certain medications can reduce costs by requiring documentation of appropriate indications for use, and where appropriate, encourage the use of less expensive agents within a drug class.

Introduction (2) Fabry disease is a rare, progressive genetic disorder characterized by a defective gene (GLA) that causes a deficiency of the enzyme, alpha-galactosidase A. This enzyme is responsible for breaking down specific lipids in lysosomes, including globotriaosylceramide (GL-3). This accumulation of GL-3 in blood vessels, kidneys, heart, nerves and other organs, leads to cell damage and consequences from mild-to-severe symptoms including kidney failure, myocardial infarctions, and strokes that can be fatal. It is estimated that 35-50% of Fabry disease patients may have an amenable GLA variant.

Dosage Form (1) Galafold™ is available in a capsule containing 123 mg of migalastat.

Manufacturer (1) Manufactured for: Amicus Therapeutics U.S., Inc., Cranbury, NJ 08512

Indication(s) (1) Galafold™ is indicated for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data. This indication is approved under accelerated approval based on reduction in kidney interstitial capillary cell GL-3 substrate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Clinical Efficacy (1,2,3) (mechanism of action/pharmacology, comparative efficacy) Migalastat is a pharmacological chaperone that reversibly binds to the active site of the alpha- galactosidase A protein (alpha-Gal A), which is deficient in Fabry disease. This binding stabilizes alpha-Gal A allowing its trafficking from the endoplasmic reticulum into the lysosome where it exerts its action.

Pharmacokinetics: Galafold™ Volume of Distribution ~89 L Excretion 77% kidney; 20% feces Clearance 12.5 L/hour Half-life ~4 hours

Clinical Trials:

FACETS

STUDY DESIGN Randomized, double-blind, placebo-controlled trial of 6 months followed by a 6 month open-label treatment phase (n=67)

INCLUSION Patient naïve to Galafold™ and ERT or previously treated with ERT and CRITERIA had been off ERT for at least 6 months

EXCLUSION Not meeting inclusion criteria CRITERIA

TREATMENT Patients were randomized 1:1 to receive Galafold™ 123 mg every other REGIMEN day or placebo for the first 6 months. In the second 6 months, all patients were treated with Galafold™

RESULTS The primary efficacy measure was the average number of GL-3 inclusions per kidney interstitial capillary in renal biopsy samples before and after treatment. At 6 months, patients treated with Galafold™ had lower plasma GL-3 levels and greater reduction in the mean number of GL-3 inclusions per kidney interstitial capillary, compared with those treated with placebo. SAFETY Not specified

ATTRACT

STUDY DESIGN 18 month, open-label comparison between Galafold™ and ERT, followed by a 12-month open-label extension with Galafold™ (n=57)

INCLUSION Patients with Fabry disease with amenable mutations in a clinical trial CRITERIA assay who had been treated with ERT for a minimum of 12 months prior to study entry

EXCLUSION Not specified CRITERIA

TREATMENT Patients were randomized 1.5:1 to switch to Galafold™ or remain on REGIMEN ERT for the primary 18-month treatment period

RESULTS The primary efficacy measure was the annual change from baseline through month 18 in GFR. Galafold™ and ERT had comparable effects on renal function in patients with amenable mutations. Left ventricular mass index decreased significantly from baseline to month 18 in Galafold™ patients whereas a smaller non-significant change was observed in patients remaining on ERT SAFETY Not specified

Contraindications (1)  None listed in packaging information

Warnings and Precautions (1)  None listed in packaging information

Adverse Effects (1)

Most common, ≥ 5% Galafold™ Placebo (n=34) (n=33) % % Headache 35% 21% Nasopharyngitis 18% 6% Urinary Tract Infection 15% 0% Nausea 12% 6% Pyrexia 12% 3% Abdominal Pain 9% 3% Back pain 9% 0 Cough 9% 0 Diarrhea 9% 3% Epistaxis 9% 3%

Drug Interactions (1)  None listed in packaging information

Dosage and Administration (1) The recommended dosage regimen of Galafold™ is 123 mg orally once every other day at the same time of day on an empty stomach. Do not consume food at least 2 hours before and 2 hours after taking Galafold™ to give a minimum 4 hours fast.

Cost

Generic Name Brand Name Manufacturer Dose Cost/Month Migalastat Galafold™ Amicus 123 mg every $26,241.90* other day

* Maximum Allowable Cost

Conclusion Galafold™ is indicated for the treatment of adults with Fabry disease who have a genetic mutation determined to be amenable to treatment with Galafold™ based on laboratory data. Galafold™ is the first oral medicine for Fabry disease, and the first new therapy approved to treat Fabry disease

in more than 15 years, when Fabrazyme, an enzyme replacement therapy, was approved. Galafold™ differs from ERT in that it increases the activity of the deficient enzyme rather than replacing it. It was approved under accelerated approval based on reduction in kidney interstitial capillary cell globotriaosylceramide substrate.

Recommendation The Division recommends adding this drug as a new clinical edit.

References 1) Galafold™ (migalastat). Retrieved 11/30/2018 from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=66dbd928-0f1c-48b1-a832- 54e4abd9f1db&audience=consumer 2) Galafold (migalastat). IPD Analytics Rx Insights_New Drug Approval Review_Galafold_09 2018.pdf 3) Journal of Medical Genetics Publishes Pivotal Phase 3 ATTRACT Study of Migalastat for Patients with Fabry Disease. Retrieved 11/30/2018 from: http://ir.amicusrx.com/news-releases/news-release-details/journal-medical-genetics- publishes-pivotal-phase-3-attract-study

Prepared by: Luke Boehmer PharmD Date: November 30, 2018