Products

Date: 2018-08-10

Type of information: Granting of a Market Authorisation in the US

Product name: Galafold®

Compound: migalastat (1-deoxygalactonojirimycin hydrochloride)

Therapeutic area: Rare diseases - Genetic diseases

Action mechanism:

• chaperone/enzyme inhibitor. Migalastat HCI is an orally-administered pharmacological chaperone developed for the treatment of Fabry disease. Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called alpha-galactosidase A (alpha-Gal A). The role of alpha-Gal A within the body is to break down specific lipids in lysosomes, including globotriaosylceramide (GL-3, also known as Gb3). Reduced or absent levels of alpha-Gal A activity leads to the accumulation of GL-3 in the affected tissues, including the kidneys, heart, central nervous system, and skin. Migalastat HCl is designed to bind to and stabilize, or "chaperone" a patient's own alpha-galactosidase A (alpha-Gal A) enzyme in those patients with genetic mutations that are amenable to this chaperone in a cell-based assay. This proprietary in vitro assay (Galafold Amenability Assay) was used to classify more than 1,000 known GLA mutations as “amenable” or “not amenable” to treatment with Galafold. Amicus estimates that 35%-50% of Fabry patients globally may have amenable genetic mutations, and amenability rates within this range vary by geography.
• Galafold® is a capsule taken once every other day, at the same time of day.

Company: Amicus Therapeutics (USA - NJ)

Disease: Fabry disease

Latest news:

• • On August 10, 2018, the FDA approved Galafold® (migalastat), the first oral medication for the treatment of adults with Fabry disease. The drug is indicated for adults with Fabry disease who have a genetic mutation determined to be responsive (“amenable”) to treatment with Galafold® based on laboratory data.  The efficacy of Galafold® was demonstrated in a six-month, placebo-controlled clinical trial in 45 adults with Fabry disease. In this trial, patients treated with Galafold® over six months had a greater reduction in globotriaosylceramide (GL-3) in blood vessels of the kidneys (as measured in kidney biopsy samples) as compared to patients on placebo.The safety of Galafold® was studied in four clinical trials which included a total of 139 patients with Fabry disease. The most common adverse drug reactions in patients taking Galafold® in clinical trials were headache, nasal and throat irritation (nasopharyngitis), urinary tract infection, nausea, and fever (pyrexia).
• Galafold ®was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is an unmet medical need and where a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. A further study is required to verify and describe the clinical benefits of Galafold®, and the sponsor will be conducting a confirmatory clinical trial of Galafold in adults with Fabry disease.
• Galafold® was granted Priority Review designation, under which the FDA’s goal is to take action on an application within six months of application filing where the agency determines that the drug, if approved, would provide a significant improvement in treating, diagnosing or preventing a serious condition over available therapies. Galafold® also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.. The FDA has approved Galafold for 348 amenable GLA variants. Galafold is the first oral medicine for Fabry disease, and the first new therapy approved to treat Fabry disease in the United States in more than 15 years.
• In the U.S., it is estimated that more than 3,000 people are living with Fabry disease, and an estimated more than 50 percent of these diagnosed patients are currently untreated. Globally, it is estimated that 35 to 50 percent of Fabry disease patients may have an amenable GLA variant.
• The FDA approval was based on data from a Phase 3 pivotal Fabry disease study in treatment-naïve patients (Study 011, or FACETS), which demonstrated the efficacy of Galafold, including a reduction in the amount of damaging disease substrate accumulated in the kidney capillaries.
• Amicus Therapeutics will launch Galafold immediately, and will begin shipping to a limited distribution network in the coming week. Amicus Assist, a service that will provide product assistance and support to patients to help gain access to Amicus Therapeutics’ medications, will also be initiated immediately. With this approval, patients in 20 countries worldwide have reimbursable access to Galafold®. Galafold® is approved in Australia, Canada, European Union, Israel, Japan, South Korea, Switzerland and the U.S. Galafold is pending approval in Taiwan. • On May 30, 2018, Amicus Therapeutics has initiated the commercial launch of Galafold® capsules 123mg (migalastat) for treatment of patients aged 16 years and older with a confirmed diagnosis of Fabry disease (alpha-galactosidase A deficiency) and who have an amenable mutation in Japan. Galafold® is the first and only oral precision medicine for Fabry disease in Japan. An estimated 850 people in Japan are living with Fabry disease. Japan represented approximately 13% of the $1.3 billion global Fabry ERT sales generated in 2017.
• Galafold® was approved by the Ministry of Health, Labour and Welfare (MHLW) under the priority review scheme allowed for an Orphan Drug. The approval was based on clinical data from completed clinical studies of Galafold®, including two Phase 3 pivotal studies in both treatment naïve (Study 011, or FACETS) and enzyme replacement therapy (ERT) switch patients (Study 012, or ATTRACT), as well as a Phase 1 study that evaluated the pharmacokinetics of migalastat in Japanese volunteers.
• • On December 14, 2017, Amicus Therapeutics submitted a new drug application (NDA) to the FDA to request approval of migalastat for the treatment of patients 16 years and older with Fabry disease who have amenable mutations. The NDA submission is based on existing clinical data, including reduction in disease-causing substrate (GL-3), as well as the totality of data from two Phase 3 pivotal studies in treatment-naïve (Study 011, or FACETS) and enzyme replacement therapy (ERT) switch patients (Study 012, or ATTRACT), as well as other completed clinical studies.
• Migalastat previously received both Orphan Drug Designation and Fast Track designation from the FDA. The FDA has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing, after which the Agency will notify the company. Amicus plans to communicate following written receipt of the Agency's decision.• On September 19, 2017, Amicus Therapeutics announced that the FDA has granted Fast Track designation for migalastat for the treatment of patients with Fabry disease with amenable mutations. Amicus Therapeutics plans to submit a New Drug Application (NDA) for migalastat in the fourth quarter of 2017.
• • On September 14, 2017, Amicus Therapeutics announced that Health Canada has approved Galafold® for long-term treatment of adults with a confirmed diagnosis of Fabry disease and who have an alpha-Gal A mutation determined to be amenable by an in vitro assay. Following the Health Canada approval, Amicus expects to make Galafold available to Canadian patients in the coming weeks.
• Health Canada approved Galafold® based on clinical data from two Phase 3 pivotal studies in both treatment naïve (Study 011, or FACETS) and enzyme replacement therapy (ERT) switch patients (Study 012, or ATTRACT), as well as an ongoing long-term extension study and overall body of evidence.
• • On August 15, 2017, Amicus Therapeutics  announced that the Australian Therapeutic Goods Administration (TGA) has approved  Galafold® for long-term treatment of adults and adolescents aged 16 years and older with a confirmed diagnosis of Fabry disease (alpha-galactosidase A deficiency) and who have an amenable mutation. Following the TGA approval, Amicus is continuing to work with the Australian reimbursement authorities to make Galafold available to Australian patients in a timely manner.
• The Australian TGA approval under the Orphan Drug program was based on clinical data from two Phase 3 pivotal studies in both treatment naïve (Study 011, or FACETS) and enzyme replacement therapy (ERT) switch patients (Study 012, or ATTRACT), as well as an ongoing long-term extension study.
• • On July 11, 2017, Amicus Therapeutics plans to submit a new drug application (NDA) to the U.S.FDA for the oral precision medicine migalastat for Fabry disease in the fourth quarter of 2017. Based on a series of discussions with and written communication received from the FDA, the Agency has informed Amicus that it may now submit an NDA for migalastat.
• Amicus is preparing the NDA submission under Subpart H, which provides for accelerated approval. Amicus intends to base its NDA on existing data, including reduction in disease-causing substrate (GL-3), as well as the totality of data from completed clinical studies. 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. An additional Phase 3 study previously requested by the Agency to assess Gastrointestinal (GI) symptoms is no longer required prior to an NDA submission. 
• • On June 28, 2017, Amicus Therapeutics has submitted a Japanese new drug application (J-NDA) to the Pharmaceuticals and Medical Devices Agency (PMDA) to request marketing authorization for migalastat, an oral precision medicine for Fabry disease. Based on a previous meeting with and written correspondence from the PMDA, the J-NDA is based upon data from completed clinical studies with migalastat, including two pivotal Phase 3 studies, as well as a Phase 1 study that evaluated the pharmacokinetics of migalastat in Japanese volunteers. Migalastat has orphan drug designation in Japan which makes it eligible for priority review as well as 10 years of market exclusivity, if approved. Based on the priority review timeline, Amicus expects a decision from the PMDA in the first half of 2018.
• • On May 2, 2017, Amicus Therapeutics has commenced the commercial launch of Galafold® in France following the publication of the price in the Official Journal. Galafold® is now reimbursed in France and dispensed via retail pharmacists as a therapy for long-term treatment of adults and adolescents aged 16 years and older with a confirmed diagnosis of Fabry disease (alpha-galactosidase A deficiency) and who have an amenable mutation.
• • On March 8, 2017, Amicus Therapeutics has commenced the commercial launch of Galafold® in Italy following the final publication of reimbursement guidelines by the Ministry of Health (Ministero della Salute). GalafoldMinistero della Salute is now reimbursed in Italy as a therapy for long-term treatment of adults and adolescents aged 16 years and older with a confirmed diagnosis of Fabry disease (alpha-galactosidase A deficiency) and who have an amenable mutation.
• • On February 27, 2017, Amicus Therapeutics has commenced the commercial launch of Galafold® in the United Kingdom (UK) following the final publication of reimbursement guidelines by the National Institute for Health and Care Excellence (NICE) Highly Specialised Technologies Evaluation Committee (EC). Galafold® is reimbursed within the National Health Service (NHS) in England as a first line therapy for long-term treatment of adults and adolescents aged 16 years and older with a confirmed diagnosis of Fabry disease (alpha-galactosidase A deficiency) and who have an amenable mutation.
• • On August 3, 2016, Amicus Therapeutics announced that the company plans to submit a Japanese new drug application (J-NDA) to request marketing authorization for migalastat, an oral precision medicine for Fabry disease, in the first half of 2017. Following a meeting with and written correspondence from the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan, the J-NDA will be based upon data from completed clinical studies with migalastat, including two pivotal Phase 3 studies, as well as a Phase 1 study that previously evaluated the pharmacokinetics (PK) of migalastat in Japanese volunteers. Taking into account data from Japanese patients included in the Phase 3 program and the similar PK properties in Japanese and non-Japanese individuals, the PMDA confirmed that these completed studies meet J-NDA submission requirements without the need to conduct an additional clinical study in Japan. Japan represents the second largest Fabry market in the world by country, with approximately 13% of the $1.2B global Fabry ERT sales generated in Japan in 2015.1 Amicus estimates that 35 percent to 50 percent of Fabry patients in Japan may have amenable genetic mutations. Amicus is currently also working with the FDA to determine the optimal approval pathway for migalastat for Fabry patients in the United States. An update is expected in the third quarter of this year.
• • On May 31, 2016, Amicus Therapeutics announced that the European Commission has granted full approval for the oral small molecule pharmacological chaperone Galafold™ (migalastat) as a first line therapy for long-term treatment of adults and adolescents aged 16 years and older with a confirmed diagnosis of Fabry disease (alpha-galactosidase A deficiency) and who have an amenable mutation. Amicus began supplying the market in Germany on Monday, May 30, 2016 and will commence the reimbursement processes with healthcare authorities in each of the major European countries. Galafold™ is the first oral treatment as well as the first precision medicine for Fabry disease. The broad label includes 269 Fabry-causing mutations which represent 35 percent to 50 percent of all patients with Fabry disease. The label also references a website www.galafoldamenabilitytable.com where EU healthcare providers can quickly and accurately determine which mutations are amenable to Galafold™. Amicus Therapeutics is also pursuing independent regulatory processes in several international territories outside of Europe, including Japan, Australia and Canada. Amicus also expects to meet with the FDA in the middle of 2016 to clarify a potential U.S. regulatory pathway for Galafold™.
• • On April 1, 2016, the European Medicines Agency (EMA) has recommended granting a marketing authorisation in the European Union (EU) for Galafold® (migalastat) for the treatment of Fabry disease.  Currently, the standard treatment for this disease is enzyme replacement therapy, which consists of an intravenous infusion of a copy of the missing enzyme. Galafold® is the first oral treatment for Fabry disease. It works in a different way to enzyme replacement therapy, acting as a 'pharmacological chaperone' which binds to the defective alpha-galactosidase A enzyme, allowing it to be transported to where its action is needed and restore its activity. Galafold® is to be used only in patients with specific mutations of the disease which are known to be responsive to the active substance in the medicine, migalastat.
• The evaluation of EMA’s Committee for Medicinal Products for Human Use (CHMP) was based on the results of two phase III clinical trials in about 110 patients with Fabry disease who had a genetic mutation which responds to migalastat (Study 011, or FACETS and Study 012, or ATTRACT ). Galafold® demonstrated its efficacy compared to placebo and to enzyme replacement therapy in a long-term comparative study. In these studies, patients taking Galafold® did not generally have troublesome side effects; the most common side effect was headache. A final decision from the European Commission (EC) is expected in the second quarter of 2016, after which Amicus Therapeutics will begin the country-by-country reimbursement processes. The label approved by the CHMP includes 269 Fabry causing mutations which represent up to half of all patients with Fabry disease.
• • On March 22, 2016, Amicus Therapeutics announced that it has initiated a reimbursed expanded access program (EAP) to provide Fabry patients who have amenable mutations with access to migalastat. The EAP will be implemented in certain territories where reimbursement can be secured prior to marketing authorization and commercial availability, beginning in France. The French National Agency for Medicines and Health Products Safety (ANSM) has granted an "Autorisation Temporaire d'Utilisation dite de cohorte" (cohort ATU), a Temporary Authorization for Use for patient sales of migalastat for Fabry patients who have amenable genetic mutations who meet the criteria for the cohort ATU.  The ATU for migalastat was granted after an assessment by the ANSM of a full application dossier that included clinical and safety data from clinical studies of migalastat. In France, patients with Fabry disease who have amenable mutations may receive treatment with migalastat before marketing authorization for the product is granted in the European Union. Government allocations to hospitals will allow payment for migalastat for patients included in the ATU program.
• • On June 25, 2015, Amicus Therapeutics announced that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) and the Centralized Procedure has begun for the oral small molecule pharmacological chaperone Galafold® (migalastat HCl) for Fabry patients who have amenable genetic mutations. As previously announced, Galafold® is the first investigational Fabry drug to be granted Accelerated Assessment in the EU. In the U.S., Amicus plans to conduct a pre-NDA meeting with the FDA and to submit a New Drug Application (NDA) for Galafold under Subpart H1 in the second half of 2015. Following the MAA validation, Amicus is also initiating the regulatory submission process in several additional geographies. Today approximately 5,000 to 10,000 individuals are diagnosed with Fabry disease; however, an estimated 40% to 50% of diagnosed patients are not currently on treatment. If approved, Amicus estimates that 30% to 50% of Fabry patients may benefit from Galafold on the basis of their genotype. Based on third party research, the Company also projects a 10% annual growth rate in diagnosis that is expected to continue.
• • On June 3, 2015, Amicus Therapeutics has submitted a marketing authorization application (MAA) to request full approval of Galafold® (migalastat HCl) for Fabry patients who have amenable genetic mutations. The brand name Galafold® has been approved by both the European Medicines Agency (EMA) as well as the U.S. Food and Drug Administration (FDA). Galafold® is the first investigational Fabry drug to be granted Accelerated Assessment in the EU. Under Accelerated Assessment, the Committee for Medicinal Products for Human Use (CHMP) may shorten the MAA review period from 210 days, under standard review, to 150 days under Accelerated Assessment. The CHMP opinion is then reviewed by the European Commission, which generally issues a final decision on EU approval within three months. The MAA submission will be reviewed in the Centralized Procedure, which if authorized, provides a marketing license valid in all 28 EU member states. Once authorized, Amicus would then begin the country-by-country reimbursement approval process. Amicus also plans to conduct a pre-NDA meeting with the US FDA and to submit a New Drug Application (NDA) for Galafold in the United States under Subpart H1 in the second half of 2015.
• Approximately 90 individuals around the world are currently being treated with Galafold as their only therapy for Fabry disease in ongoing long-term extension studies. Amicus previously reported positive Phase 3 data for Galafold in both treatment naïve (Study 011, or FACETS) and enzyme replacement therapy (ERT) switch patients (Study 012, or ATTRACT ). Results from these studies have shown that treatment with Galafold has resulted in reductions in disease substrate, stability of kidney function, reduction in cardiac mass, and a positive impact on patient-reported outcomes in patients with amenable mutations.
• • On May 26, 2015, Amicus Therapeutics announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted Accelerated Assessment to migalastat monotherapy for Fabry patients who have amenable genetic mutations. Migalastat is the first investigational Fabry drug to be granted Accelerated Assessment. Amicus requested Accelerated Assessment in accordance with the EMA guidelines, which justify Accelerated Assessment for therapies that are expected to be of major public health interest and therapeutic innovation, addressing the greater unmet needs for maintaining and improving the health of the Community. Amicus is on track to submit the MAA to request full approval for migalastat monotherapy in the EU in the second quarter of 2015.
• • On March 19, 2015, Amicus Therapeutics, a biopharmaceutical company at the forefront of therapies for rare and orphan diseases, announced that it has met very recently with regulatory authorities in Europe and the U.S. to discuss the approval pathways for migalastat as a precision medicine monotherapy for Fabry patients who have amenable genetic mutations. Amicus held a meeting with the assigned European Rapporteurs to discuss the upcoming marketing authorization application (MAA) for migalastat monotherapy. Amicus Chief Medical Officer Dr. Jay Barth led the Amicus delegation at the meeting in Europe last week. It was the first face-to-face meeting with the assigned Rapporteurs on the proposed dossier for migalastat monotherapy. The European Medicines Agency (EMA) assigns Rapporteurs to review the data in the MAA in detail and to provide guidance to sponsors during the regulatory approval process. The meeting was highly successful for Amicus. The Rapporteurs commented favorably upon the quality and quantity of the migalastat data submitted, which included data from the two largest Phase 3 studies ever conducted in Fabry disease and over 400 patient years of data. They also noted that the Amicus clinical development plan followed the prior scientific guidance from EMA. The Rapporteurs agreed that Amicus may submit its MAA for migalastat monotherapy under the Full Approval pathway in the EU. They indicated support for Amicus to request Accelerated Assessment in view of the migalastat data and the major public health interest that exists for Fabry patients.Based on this feedback and other positive comments from the EU Regulatory officials, Amicus is accelerating the timing of the MAA submission for full approval for migalastat monotherapy from the middle of 2015 to the second quarter of 2015.
• Amicus also held a Type C meeting with the FDA earlier this week to review results from both Phase 3 Fabry clinical studies (Study 011 - FACETS and Study 012 - ATTRACT ) and to discuss the U.S. approval pathway for migalastat. Amicus and FDA officials discussed the migalastat monotherapy data, multiple potential approvable endpoints, and a path toward NDA submission under Subpart H. Dr. Barth also led the Amicus delegation for this meeting which also included one of the world's foremost Fabry nephrology experts. The key takeaways from the meeting include: Amicus plans to submit an NDA for Accelerated Approval (Subpart H), which is only available to therapies for severe and life-threatening conditions that address significant unmet medical needs.  For Accelerated Approval, FDA is open to considering several potential surrogate endpoints evaluated in the clinical studies of migalastat, including: Substrate reduction (interstitial capillary GL-3), Reduction in cardiac mass (left ventricular mass index, LVMi), Stabilization of kidney function (glomerular filtration rate), A post-approval (Phase 4) confirmatory study is required under Subpart H, and several potential protocol designs were discussed. Amicus plans to schedule a pre-NDA meeting and to submit an NDA under Subpart H in the second half of 2015.
• • On December 11, 2014, Amicus Therapeutics announced that it has conducted a successful pre-submission meeting with the European Medicines Agency (EMA) to discuss the registration of migalastat monotherapy for the treatment of Fabry disease. Amicus has begun preparing a marketing authorization application (MAA) that it plans to submit to the EMA in the middle of 2015 under the Centralized Procedure.

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE: 2015-06-03

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2018-08-10

UE authorization: 2016-05-26

Favourable opinion UE: 2016-04-01

Favourable opinion USA:

Orphan status USA: 2004-02-25

Orphan status UE: 2006-05-22

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes