MAA Submission for Full Approval Planned in European Union -- Company to Accelerate Submission Timeline for MAA Filing to 2Q15
NDA Submission for Accelerated Approval (Subpart H) Planned in United States for 2H15
CRANBURY, N.J., March 19, 2015 -- Amicus Therapeutics (FOLD), a biopharmaceutical company at the forefront of therapies for rare and orphan diseases, today announced that it has met very recently with regulatory authorities in Europe and the U.S. to discuss the approval pathways for the oral small molecule pharmacological chaperone migalastat HCl ("migalastat") as a precision medicine monotherapy for Fabry patients who have amenable genetic mutations.
Meeting with European Rapporteurs
The Company 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 key takeaways from the meeting include:
- Acknowledgment from the Rapporteurs of the continued significant unmet need in Fabry disease, and the need for innovative treatment options such as migalastat monotherapy
- 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
- The Rapporteurs 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
- The Rapporteurs indicated support for Amicus to request Accelerated Assessment1 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.
Type C Meeting with U.S. Food and Drug Administration (FDA)
Amicus held a Type C meeting with the FDA earlier this week to review results from both Phase 3 Fabry clinical studies (Study 011 and Study 012) 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 needs2
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
John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, Inc., stated, "We are very pleased with these recent regulatory interactions. These regulatory discussions demonstrate that health officials in both the U.S. and EU recognize the continued life threatening medical challenges that people living with Fabry face each day. It has been a stellar example of industry and regulators working together to evaluate data and to determine the best and fastest ways in which to bring novel therapies to people in need, especially in such a rare and devastating disease like Fabry. The Amicus team is working tirelessly to submit the highest quality submission to the EU in the next quarter and to the United States in the second half of this year. This is another great step forward for people living with Fabry and the potential for a new precision medicine to treat their disease."
Amicus previously reported positive Phase 3 data in both treatment naive (Study 011, or FACETS) and enzyme replacement therapy (ERT) switch patients (Study 012, or ATTRACT). Results from these studies have shown that treatment with migalastat 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.
Conference Call and Webcast
Amicus Therapeutics will host a conference call and audio webcast today, March 19, 2015 at 8:00 a.m. ET to discuss the global regulatory strategy for migalastat monotherapy for Fabry disease. Interested participants and investors may access the conference call at 8:00 a.m. ET by dialing 877-303-5859 (U.S./Canada) or 678-224-7784 (international).
An audio webcast can also be accessed via the Investors section of the Amicus Therapeutics corporate web site at http://www.amicusrx.com, and will be archived for 30 days. Web participants are encouraged to go to the web site 15 minutes prior to the start of the call to register, download and install any necessary software. A telephonic replay of the call will be available for seven days beginning at 11:00 a.m. ET today. Access numbers for this replay are 855-859-2056 (U.S./Canada) and 404-537-3406 (international); participant code 11357362.
About Study 011 (FACETS)
Study 011 was a Phase 3 study designed to measure the reduction of disease substrate (globotriaosylceramide, or GL-3) following treatment with migalastat in Fabry patients with amenable mutations. The study also measured clinical outcomes, including renal function and LVMi, as secondary endpoints.The 24-month study began with a 6-month double-blind, placebo-controlled treatment period, after which all patients were treated with migalastat for a 6-month open-label follow-up period and a subsequent 12-month open-label extension phase.
Fabry patients enrolled in Study 011 were naive to treatment or had not received ERT for at least 6 months prior to study entry. Upon completion, patients were eligible to roll over into a separate extension Study (Study 041) to continue migalastat.
About Study 012 (ATTRACT)
Study 012 was a Phase 3, open-label study that compared oral migalastat to standard-of-care ERTs for Fabry disease (Fabrazyme(R) and Replagal(R)). The study enrolled 60 patients (26 males and 34 females) with Fabry disease with amenable mutations in a clinical trial assay who had been treated with ERT for a minimum of 12 months prior to study entry. These patients were randomized 1.5:1 to switch to migalastat (36 patients) or remain on ERT (24 patients) for the primary 18-month treatment period, after which they were eligible to receive migalastat in a 12-month extension phase.
The co-primary outcome measures were the mean annualized changes in estimated glomerular filtration rate (eGFR) and measured (iohexol) GFR (mGFR) assessed by descriptive comparisons of migalastat and ERT over 18 months. Secondary outcome measures included LVMi, as well as a composite of Fabry-associated clinical events (i.e. renal, cardiac, or cerebrovascular).
About GLP HEK-Amenable Mutations
Amenable mutations are defined as having an absolute increase of 3% of wild type alpha-Gal A enzyme activity and a relative increase of 20% when exposed to migalastat in a cell-based in vitroassay. All patients enrolled in Study 011 and Study 012 had amenable mutations in the clinical trial HEK assay available at study initiation ("clinical trial assay"). Following the completion of enrollment, a GLP HEK assay was developed with a third party to measure the criteria for amenability with more quality control and rigor. However, approximately 10% of mutations in the HEK database switched categorization between "amenable" and "non-amenable" when moving from the clinical trial assay to the GLP HEK assay. Therefore there were changes in categorization from amenable to non-amenable in 17 patients in Study 011, and in 4 patients in Study 012.
Overall based on results from mutations tested in the GLP HEK assay, Amicus continues to believe that approximately 30% to 50% of the Fabry population have mutations that are amenable to migalastat.
About Amicus Therapeutics
Amicus Therapeutics (FOLD) is a biopharmaceutical company at the forefront of therapies for rare and orphan diseases. The Company is developing novel, first-in-class treatments for a broad range of human genetic diseases, with a focus on delivering new benefits to individuals with lysosomal storage diseases. Amicus' lead programs in development include the small molecule pharmacological chaperone migalastat as a monotherapy for Fabry disease, as well as next-generation enzyme replacement therapy (ERT) products for Fabry disease, Pompe disease, and MPS-1.
1Guideline to The Procedure for Accelerated Assessment, www.ema.europa.eu
2CFR - Code of Federal Regulations Title 21, www.fda.gov
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to preclinical and clinical development of Amicus' candidate drug products, the timing and reporting of results from preclinical studies and clinical trials evaluating Amicus' candidate drug products and the projected cash position for the Company. Words such as, but not limited to, "look forward to," "believe," "expect," "anticipate," "estimate," "intend," "potential," "plan," "targets," "likely," "may," "will," "would," "should" and "could," and similar expressions or words identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. The inclusion of forward-looking statements should not be regarded as a representation by Amicus that any of its plans will be achieved. Any or all of the forward-looking statements in this press release may turn out to be wrong. They can be affected by inaccurate assumptions Amicus might make or by known or unknown risks and uncertainties. For example, with respect to statements regarding the goals, progress, timing and outcomes of discussions with regulatory authorities and the potential goals, progress, timing and results of preclinical studies and clinical trials, actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in the business of Amicus, including, without limitation: the potential that results of clinical or pre-clinical studies indicate that the product candidates are unsafe or ineffective; the potential that it may be difficult to enroll patients in our clinical trials; the potential that regulatory authorities may not grant or may delay approval for our product candidates; the potential that preclinical and clinical studies could be delayed because we identify serious side effects or other safety issues; the potential that we will need additional funding to complete all of our studies and, our dependence on third parties in the conduct of our clinical studies. Further, the results of earlier preclinical studies and/or clinical trials may not be predictive of future results. With respect to statements regarding projections of the Company's cash position, actual results may differ based on market factors and the Company's ability to execute its operational and budget plans. In addition, all forward looking statements are subject to other risks detailed in our Annual Report on Form 10-K for the year ended December 31, 2014. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and Amicus undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.