Amicus Therapeutics Announces U.S. Regulatory Pathway for Migalastat for Fabry Disease
Regulatory Plan for Full Approval Pathway Based on
Generation of Additional Gastrointestinal Symptoms Data
Intermediate Expanded Access Program Expected to Begin in 2017
Conference Call Today at
Key elements of the additional data generation required for full approval of migalastat in
- Randomized, 12-month, placebo-controlled pivotal "cross-over" study in treatment naïve Fabry patients who have an amenable mutation and GI symptoms
- Crossover study design provides sufficient powering with a small number of patients (~35 patients planned)
- Primary endpoint to assess diarrhea based upon established
FDA irritable bowel syndrome (IBS) guidance1 - Amicus is working with
FDA to finalize the clinical protocol and plans to initiate enrollment in 2017, with data expected in 2019 - Upon successful NDA filing, the review will be based upon these new data and the totality of the data from all prior migalastat studies
- Intermediate Expanded Access Program (EAP) planned to ensure short-term access to migalastat for
U.S. patients who are currently on ERT and meet EAP requirements U.S. patients currently enrolled in ongoing clinical extension studies will continue to receive migalastat
During its review of the briefing document submitted and in discussions with Amicus, the
More than 50% of patients with Fabry disease report or show GI signs and symptoms, including diarrhea, abdominal pain, constipation, nausea, and vomiting.2 Amicus previously presented positive GI data in a completed Phase 3 randomized, placebo controlled Study 011 (FACETS) in treatment-naïve Fabry patients with amenable mutations. The GI data from this study showed a significant decrease in diarrhea (unadjusted p=0.03) in patients with amenable mutations treated with migalastat versus placebo during the 6-month double-blind phase (Stage 1), which persisted after 18-24 months of treatment with migalastat.
"There are significant unmet needs and a lack of treatment choices for people living with Fabry disease in the U.S.," said
The U.S. market for migalastat is estimated to be approximately 25% of the global opportunity.
Migalastat is designed to selectively and
reversibly bind with high affinity to the active sites of certain mutant forms of alpha-Gal A, the genotypes of which are referred to as amenable mutations. On
Conference Call and Webcast
An audio webcast can also be accessed via the Investors section of the
About Galafold™ and Amenable Mutations
Galafold™ (migalastat) is a first-in-class chaperone therapy approved in the EU as a monotherapy for Fabry disease in patients with amenable mutations. Galafold works by stabilizing the body's own dysfunctional enzyme, so it can clear the accumulation of disease substrate in patients who have amenable mutations. A proprietary in vitro assay (Galafold Amenability Assay) was used to classify more than 800 known GLA mutations as "amenable" or "not amenable" to treatment with Galafold. The current EU label includes 313 GLA mutations that have been identified
and determined to be amenable based on the Galafold Amenability Assay, which represent between 35% and 50% of the currently diagnosed Fabry population.
Healthcare providers in the EU may access the website www.galafoldamenabilitytable.com to quickly and accurately identify which mutations are categorized as "amenable" or "not amenable" to Galafold. Amicus expects to submit updates to the label as additional GLA mutations are identified and tested in the Galafold Amenability Assay.
Important Safety Information from the EU
Approval
Treatment with GALAFOLD should be initiated and supervised by specialists experienced in the diagnosis and treatment of Fabry disease. GALAFOLD is not recommended for use in patients with a nonamenable mutation.
- GALAFOLD is not intended for concomitant use with enzyme replacement therapy.
- GALAFOLD is not recommended for use in patients with Fabry disease who have severe renal impairment ( < 30 mL/min/1.73 m2). The safety and efficacy of GALAFOLD in children 0-15 years of age have not yet been established.
- No dosage adjustments are required in patients with hepatic impairment or in the elderly population.
- There is very limited experience with the use of this medicine in pregnant women. If you are pregnant, think you may be pregnant, or are planning to have a baby, do not take this medicine until you have checked with your doctor, pharmacist, or nurse.
- While taking GALAFOLD, effective birth control should be used. It is not known whether GALAFOLD is excreted in human milk.
- Contraindications to GALAFOLD include hypersensitivity to the active substance or to any of the excipients listed in the PRESCRIBING INFORMATION.
- It is advised to periodically monitor renal function, echocardiographic parameters and biochemical markers (every 6 months) in patients initiated on GALAFOLD or switched to GALAFOLD.
- OVERDOSE: General medical care is recommended in the case of GALAFOLD overdose.
- The most common adverse reaction reported was headache, which was experienced by approximately 10% of patients who received GALAFOLD. For a complete list of adverse reactions, please review the SUMMARY OF PRODUCT CHARACTERISTICS.
- Call your doctor for medical advice about side effects.
For further important safety information for Galafold, including posology and method of administration, special warnings, drug interactions and adverse drug reactions, please see the European SmPC for Galafold available from the EMA website at www.ema.europa.eu.
About Fabry Disease
Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called alpha-galactosidase A (alpha-Gal A), which is the result of mutations in the GLA gene. The primary biological function of
alpha-Gal A is to degrade specific lipids in lysosomes, including globotriaosylceramide (referred to here as GL-3 and also known as Gb3). Lipids that can be degraded by the action of alpha-Gal A are called "substrates" of the enzyme. Reduced or absent levels of alpha-Gal A activity lead to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, and skin. Progressive accumulation of GL-3 is believed to lead to the morbidity and mortality of Fabry disease, including pain, kidney failure, heart disease, and stroke. The symptoms can be severe, differ from patient to patient, and begin at an early age. All Fabry disease is progressive and may lead to organ damage regardless of the time of symptom onset.
About
1 http://www.fda.gov/downloads/Drugs/.../Guidances/UCM205269.pdf
2 Hoffmann B et al. Clin Gastroenterol Hepatol.
2007;5(12):1447-1453.
Forward-Looking Statements
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