Amryt Pharma Plc, a commercial-stage biopharmaceutical company, focuses on acquiring, developing and commercializing treatments to help improve the lives of patients with rare and orphan diseases.
The company’s portfolio includes two commercial rare disease products, as well as a development-stage pipeline focused on rare skin diseases.
The company’s two commercial products, lomitapide for the treatment of homozygous familial hypercholesterolemia (HoFH), and metreleptin for the treatment of ge...
Amryt Pharma Plc, a commercial-stage biopharmaceutical company, focuses on acquiring, developing and commercializing treatments to help improve the lives of patients with rare and orphan diseases.
The company’s portfolio includes two commercial rare disease products, as well as a development-stage pipeline focused on rare skin diseases.
The company’s two commercial products, lomitapide for the treatment of homozygous familial hypercholesterolemia (HoFH), and metreleptin for the treatment of generalized lipodystrophy (GL) and partial lipodystrophy (PL), have each been sold globally through its commercial infrastructure for approximately five years.
The company is developing its lead product candidate, Oleogel-S10, for the treatment of cutaneous manifestations of severe Epidermolysis Bullosa (EB), a rare and devastating genetic skin disease for which there is no approved therapy. Filsuvez is the approved brand name for Oleogel-S10, which has not received regulatory approval by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for the treatment of EB. It received positive topline data from the pivotal Phase 3 EASE trial of Oleogel-S10.
The company’s next product candidate, AP103, is in preclinical development for the treatment of patients with Recessive Dystrophic EB (RDEB), a subset of EB. AP103 is a gene therapy product candidate based on the company’s novel polymer-based topical gene therapy delivery platform, which also has potential use for the treatment of other rare genetic diseases. In September 2020, the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products (COMP) adopted a positive opinion for orphan designation for the use of AP103 in Epidermolysis Bullosa (EB). In December 2020, the FDA granted orphan drug designation for AP103 for the treatment of Dystrophic EB (DEB), a subset of EB. The company intends to initiate clinical development of AP103 in 2022. It has a proven track record of obtaining rare disease assets, either through acquisition or in-license, and the company intends to continue building its portfolio of rare disease programs with the focus of bringing effective treatments to patients in need.
Lomitapide is an oral therapy approved as an adjunct to a low-fat diet and other lipid-lowering treatments for adults with HoFH. It is marketed in the United States under the trade name JUXTAPID and in the European Union (EU) under the trade name LOJUXTA. Lomitapide is a small molecule microsomal triglyceride transfer protein inhibitor. In December 2020, the company received a marketing authorization approval from Agencia Nacional De Vigilancia Sanitaria, the Brazilian Health Regulatory Agency for LOJUXTA.
Metreleptin for injection is approved in the United States under the trade name MYALEPT as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired GL. It is approved in the EU under the trade name MYALEPTA for the treatment of leptin deficiency in patients with congenital or acquired GL and familial or acquired PL for whom standard treatments have failed to achieve adequate metabolic control. Metreleptin is a recombinant human leptin analog that binds to and activates the human leptin receptor. Metreleptin acts to stimulate fatty acid oxidation throughout the body and lower plasma, hepatic and myocellular triglyceride levels.
The company intends to continue to evaluate additional expansion opportunities for its products. It is conducting a Phase 3 pediatric study in Europe, the Middle East and Africa (EMEA) for the use of lomitapide in children and adolescents with homozygous familial hypercholesterolemia (HoFH), for which it intends to report data in the first half of 2022. The company is also exploring the potential use of lomitapide to treat patients with familial chylomicronemia syndrome (FCS), which is a severe, rare genetic lipid disease characterized by extremely elevated levels of triglycerides, or hypertriglyceridemia. An investigator-led open-label Phase 2 trial studying lomitapide in patients with FCS is ongoing and it intends to report data in the first quarter of 2021. Upon successful completion of this Phase 2 study, the company intends to discuss these results with the FDA and the EMA in the context of agreeing on the design of a potential pivotal trial in FCS.
The company is conducting a pivotal Phase 3 clinical trial of Oleogel-S10 in severe EB, including DEB and Junctional EB (JEB). In 2019, it reported that the independent Data and Safety Monitoring Board (DSMB) performed a pre-specified unblinded interim efficacy analysis and recommended the continuation of the study with an increase in enrollment from 182 to 230 evaluable patients to maintain 80% conditional statistical power. The company received positive topline results from the EASE trial in September 2020.
Oleogel-S10 has been granted Pediatric Rare Disease Designation by the FDA. If the New Drug Application (NDA) is granted a priority review and subsequently results in an approval from the FDA, it is eligible to apply for a Priority Review Voucher (PRV) that the company can use, sell or transfer. It is also supporting an investigator-led Phase 2 study of Oleogel-S10 for the treatment of severe radiation-induced dermatitis. This trial is expected to commence in the first half of 2021, with data expected in 2022.
The company also has a novel polymer-based topical gene therapy delivery platform for potential use in the treatment of rare genetic diseases. Its first product candidate utilizing this platform, AP103, is in preclinical development for the treatment of Recessive Dystrophic EB (RDEB), a subset of severe EB. The company intends to initiate clinical development for AP103 in 2022. In September 2020, the EMA’s COMP adopted a positive opinion for orphan designation for the use of AP103 in EB. In December 2020, the FDA granted orphan drug designation for AP103 for the treatment of DEB.
The company sells lomitapide and metreleptin in the Americas, Europe and the Middle East through its existing rare disease commercial infrastructure. The company’s commercial expertise includes market access, marketing, sales managers and sales representatives and is supported by its experienced medical affairs team with medical science liaisons, patient advocates and dieticians in the field. The company also has a network of third-party distributors in other key markets throughout the world.
Sales and Marketing
In the United States, the company’s sales team promotes Myalept to healthcare professionals for the treatment of GL patients, and JUXTAPID for the treatment of adult HoFH patients. The major frequent physician call points for the company’s products are endocrinologists (including pediatric endocrinologists) with respect to Myalept and lipidologists and cardiologists with respect to Juxtapid.
The company’s sales and marketing efforts also focus on obtaining market access for its products, which primarily represents securing pricing and reimbursement approvals at acceptable levels. In the United States, the company mobilizes a team supporting market access initiatives with the primary responsibility of collaborating with insurance plans, health maintenance organizations and other payers on securing reimbursement and formulary status for Myalept and Juxtapid.
Outside the United States, the company supports this effort primarily through the work of country managers and local consultants. It has secured market access for both lomitapide and metreleptin in certain key EU and LATAM countries. The company also continues to submit market access dossiers in other EU and LATAM countries where reimbursement has not occurred, as of December 31, 2020.
Distribution
In the United States, lomitapide and metreleptin are distributed exclusively through Accredo Health Group, Inc. (Accredo), through a specialty pharmacy network that provides the products directly to patients and, under limited circumstances, to other U.S. purchasers. The specialty pharmacy takes title upon delivery of products. It also provides certain patient program support services. For commercial sales outside the United States, including sales of Myalepta and Lojuxta, named patient sales and other expanded access distribution, the company uses its existing infrastructure and third party providers to distribute products either directly to the purchaser in the applicable country or to its local third party distributor or service provider for such country.
Intellectual Property
The company has a portfolio of patents and pending patent applications covering various aspects of its lomitapide, metreleptin, Oleogel-S10 and AP103 assets in a variety of jurisdictions. Its lomitapide patent portfolio includes eight Approved Drug Products with Therapeutic Equivalence Evaluations (‘Orange Book’) listed patents licensed from the University of Pennsylvania (UPenn) claiming methods of treatment that provide protection from 2025 to 2027 in the United States and into 2025 in Europe, Australia, Japan, South Korea and New Zealand. Applications are pending in the U.S. Canada and India. Supplementary protection certificates (SPCs) have been granted in 22 European countries (including the United Kingdom, Germany, France, Italy and Spain) extending patent protection into 2028. Six additional SPCs applications are pending.
The metreleptin patent portfolio includes two issued U.S. patents claiming methods of treating lipoatrophy, two granted European patents (EP patents) claiming methods of treatment (validated in various European countries, including the United Kingdom, Germany, France, Italy and Spain), granted patents claiming methods of treatment in other jurisdictions, including Australia, Canada, and Japan, as well a pending applications in the United States, all of which have been licensed to the company or are owned by it. The granted patents provide protection from 2022 to 2027 in the United States and into 2022 in Europe and other jurisdictions. A U.S. patent application claiming methods of detecting anti-leptin neutralizing antibodies provides protection until 2038. Additional applications claiming methods of detecting anti-leptin neutralizing antibodies are pending in the United States, Brazil, Canada, China, Eurasia, India, Japan and Mexico; if granted, patent protection would expire in 2037.
The company were first granted patent protection for Oleogel-S10 in Japan in 2010. Key patent grants for Oleogel-S10 in Europe and the United States followed in 2013. If Oleogel-S10 is approved in the U.S. the company’s Oleogel-S10 patent portfolio includes one U.S. patent that will be listable on the Orange Book covering oleogel compositions providing exclusivity in the United States to 2025 and two U.S. patents that will be listable on the Orange Book covering treatment of EB that provide exclusivity in the United States into 2030. Its non-U.S. patents for Oleogel-S10, include EP patents (validated in various European countries, including the United Kingdom, Germany, France, Italy and Spain) covering the Oleogel-S10 composition and methods of healing wounds with Oleogel-S10, expiring in 2025 and 2030, respectively. Supplementary protection certificates have been obtained in various EU countries, extending the expiration of the composition patents in Europe from 2025 to 2030. The company has filed a further international patent application directed to the clinical formulation and methods of manufacturing and treatment therewith; the term of any patents that are derived from this application would expire in 2039.
The AP103 patent portfolio includes one granted EP patent (validated in various countries, including the United Kingdom, Germany, France, Italy and Spain) claiming HPAE polymers and polyplexes comprising HPAE polymers, and transfection methods using such polymers, as well as pending the U.S. and European applications. These patents and applications have been in-licensed from the University College Dublin, National University of Ireland (University College Dublin), and are expected to provide exclusivity into 2035. It has also filed an international application claiming a proprietary genus of HPAEs and novel HPAE polyplexes, as well as an international application claiming a proprietary and scalable HPAE polyplex manufacturing methods; the term of any patents that are derived from these applications would expire in 2039.
Juxtapid was granted Orphan Drug status in the United States for the treatment of HoFH and for the treatment of FCS. This designation provided exclusivity to December 2019 for the approved HoFH indication and can provide potentially seven years of exclusivity for the FCS indication, if that indication is approved. Lojuxta obtained Orphan Drug status in the European Union for the treatment of FCS. Upon approval of an FCS indication in the European Union, 10 years of exclusivity (plus two years on successful completion of a pediatric investigation plan (PIP)) could be obtained.
Following approval by the EMA in July 2018, metreleptin is entitled to ten years of market and Orphan Drug exclusivity in the European Union (to July 2028 which can be extended a further two years upon successful completion of a PIP) for the treatment of familial partial lipodystrophy, Barraquer-Simons syndrome, Lawrence syndrome, and Berardinelli-Seip syndrome. In the United States Myalept should also qualify for a 12-year period of exclusivity from biosimilar or interchangeable products, which will expire in 2026, under the Biologics Price Competition and Innovation Act. Myalept could also receive orphan designation upon submission and approval of a PL indication in the United States, which would provide seven years of exclusivity for this indication following approval in the United States.
Oleogel-S10 has been granted Orphan Drug status for the treatment of EB in the European Union and the United States. Should Oleogel-S10 be granted approval it will be entitled to Orphan Drug exclusivity for the treatment of EB, extending protections for seven years in the United States and ten years in the European Union from the date of approval in the respective jurisdictions. The ten-year Orphan Drug exclusivity period in the European Union can be extended a further two years upon successful completion of a PIP.
Agreement
University College Dublin In-License Agreement
In 2018, Amryt Genetics Limited entered into an agreement with University College Dublin relating to the patent rights for AP103. Under this agreement, University College Dublin granted an exclusive, worldwide license to the patent rights for the platform technology to develop one or more gene therapy products for therapeutic use in various disorders in humans and animals. University College Dublin retains an irrevocable, perpetual, royalty-free, worldwide right to use the licensed intellectual property for the purposes of academic teaching, publication and non-commercial research. The company intends to conduct various preclinical studies in connection with the agreement.
UPenn Lomitapide License Agreement
In 2006, Aegerion entered into an agreement with UPenn for the in-license of lomitapide. Pursuant to the terms of the agreement Aegerion was granted an exclusive and worldwide license (including right to sublicense) to certain patents of UPenn and certain patents assigned to UPenn by Bristol-Myers Squibb (Bristol-Myers). The license is provided for the following field of use: monotherapy or with other dyslipidemic therapies to treat patients with HoFH; and monotherapy or in combination with other dyslipidemic therapies for treatment of patients with other severe forms of hypercholesterolemia unable to come within 15% of National Cholesterol Education Program’s (NCEP) goal on maximal tolerated oral therapy, as determined by the patient’s prescribing physician, with severe combined hyperlipidemia unable to come within 15% of NCEP’s non-high-density lipoprotein-cholesterol goal on maximal tolerated oral therapy, as determined by the patient’s prescribing physician, or with severe hypertriglyceridemia unable to reduce triglycerides of approximately 1,000 on maximal tolerated therapy.
Japan Lomitapide License Agreement
In 2019, Aegerion entered into a license agreement with Recordati Rare Diseases Inc. (Recordati) for the commercialization of Juxtapid in Japan. Under the terms of the license agreement, and subject to the conditions set forth therein, Aegerion granted to Recordati an exclusive license in Japan, for the current marketed indication for HoFH. During the term of the license agreement, Recordati also has an exclusive right of first negotiation to any new indications for Juxtapid in Japan that might be developed by Aegerion and the right to grant sub-licenses and to manufacture and commercialize Juxtapid, under specific circumstances.
Metreleptin Asset Purchase Agreements
In 2014, Aegerion entered into an asset purchase agreement relating to the acquisition from Amylin Pharmaceuticals, LLC (Amylin) and AstraZeneca Pharmaceuticals LP (AstraZeneca), an affiliate of Amylin, of certain assets and rights associated with the biological product metreleptin for injection.
In 2015, Aegerion entered into a letter agreement with AstraZeneca and Bristol-Myers, which was subsequently amended on April 30, 2015. This agreement was entered into pursuant to Aegerion’s acquisition of metreleptin from AstraZeneca. Under the asset purchase agreement and letter agreement, Aegerion agreed to fulfill certain of AstraZeneca’s original obligations to Bristol-Myers, including reporting, milestone and royalty payments and diligence obligations in relation to metreleptin.
Amgen License Agreement
In connection with Aegerion’s acquisition of metreleptin in 2015, Aegerion acquired a license agreement between Amgen, Inc. (Amgen) and Amylin Pharmaceuticals, LLC, dated February 7, 2006 (‘Amgen License’) pursuant to which Aegerion obtained an exclusive worldwide license from Amgen to certain know-how and patents and patent applications covering the composition of matter and methods of use of metreleptin to develop, manufacture and commercialize a preparation containing metreleptin (‘Amgen Licensed Products’).
As part of the Amgen License, Aegerion also obtained an exclusive sublicense of Amgen’s exclusive rights to certain metreleptin-related patents and patent applications owned by the Rockefeller University and exclusively licensed to Amgen under a license agreement dated April 14, 1995, as amended (Rockefeller License) and an exclusive sublicense of Amgen’s non-exclusive rights to certain metreleptin-related patents and patent applications owned by The Regents of the University of California and non-exclusively licensed to Amgen under a license agreement dated July 13, 2005 (UCSF License). Amgen retains rights to conduct research, development, manufacturing and commercialization activities with respect to products other than the Amgen Licensed Products.
National Institutes of Health (NIH) License Agreement
In 2017, Aegerion entered into an in-license agreement in respect of patent rights for metreleptin with the NIH. Pursuant to the terms of the agreement Aegerion was granted an exclusive and worldwide license to (including the right to sub-license) the NIH patent rights for the use of leptin, leptin analogs and derivatives for the diagnosis, prevention and treatment of human lipodystrophy.
Accredo Agreements
In 2013, Aegerion entered into a distribution agreement in respect of lomitapide with Accredo. Pursuant to the agreement Accredo is appointed as an authorized non-exclusive distributor of record of lomitapide. In 2013, Aegerion entered into a master services agreement in respect of metreleptin with Accredo.
Research and Development
The company’s research and development expenses for the year ended December 31, 2020 were $27.6 million.
Government Regulation
The company’s products must be approved by the FDA through the NDA or the BLA process before they might be legally marketed in the United States, and must be approved by foreign regulatory authorities through various procedures before they could be marketed in the applicable country, including the EMA or the regulatory authorities of the EU Member States before they could be placed on the market in the European Union.
The company and its third-party manufacturers are subject to Good Manufacturing Practice (GMP), which are regulations governing manufacturing processes, stability testing, record keeping and quality standards as defined by the EMA, the European Commission (EC), the competent authorities of EU Member States and other regulatory authorities.
History
Amryt Pharma plc was founded in 2015. The company was incorporated in 2019.
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