Endo International Profile
Endo International plc operates as a specialty pharmaceutical company.
The company’s focus is on pharmaceutical products and it targets areas where can build leading positions. The company’s operating model is based on a lean and nimble structure, the rational allocation of capital and an emphasis on high-value research and development (R&D) targets.
The company’s sales and marketing activities are based in the U.S. and Canada and primarily focus on the promotion of its Specialty Products portfolio and Sterile Injectables segment.
The company markets its Specialty Products directly to specialty physicians, including those specializing in urology, orthopedics, pediatric endocrinology and bariatric surgery. The company’s sales force also directs its marketing efforts on retail pharmacies and other healthcare professionals. The company distributes its Specialty Products through independent wholesale distributors, but it also sells directly to retailers, clinics, government agencies, doctors, independent retail and specialty pharmacies and independent specialty distributors. The company’s marketing policy is designed to provide physicians, pharmacies, hospitals, public and private payers and appropriate healthcare professionals with products and appropriate medical information. The company works to gain access to various formularies (lists of recommended or approved medicines and other products) and reimbursement lists by demonstrating the qualities and treatment benefits of its products within their approved indications.
In addition to advertising in professional journals, participating in medical meetings and conventions and utilizing direct mail and internet programs to provide descriptive product literature and scientific information, the company has also utilized both branded and unbranded marketing and public relations campaigns across digital, social and television platforms to reach its target consumers. For example, during the first quarter of 2022, the company launched a new Dupuytren’s contracture (DC) condition awareness campaign featuring real patients and, during the fourth quarter of 2021, the company launched a new multi-channel branded advertising campaign for XIAFLEX for the treatment of Peyronie’s disease (PD), including its first-ever television commercial for XIAFLEX.
The company’s dedicated Sterile Injectables sales and marketing team is focused on health systems and national group purchasing organizations (GPOs). The company’s customers’ growing complexity requires it to engage directly with key stakeholders and decision makers. The company’s experienced sales and marketing team is key to growing its existing portfolio and executing on new product launches.
Segments
The company operates through four segments: Branded Pharmaceuticals; Sterile Injectables; Generic Pharmaceuticals; and International Pharmaceuticals.
For branded products, which the company sells primarily through its Branded Pharmaceuticals and Sterile Injectables segments, it seeks to invest in products or product candidates that have inherent scientific, regulatory, legal and technical complexities and market such products under recognizable brand names that are trademarked.
For products the company develops for the U.S. market, after the completion of required clinical trials and testing, it seeks approvals from regulatory bodies such as through the submission of New Drug Applications (NDAs) or Biologics License Applications (BLAs) to the U.S. Food and Drug Administration (FDA).
Generic products are the pharmaceutical and therapeutic equivalents of branded products and is generally sold under their generic (chemical) names rather than their brand names. For generic products, which the company sells primarily through its Sterile Injectables and Generic Pharmaceuticals segments, its focus is on high-barrier-to-entry products, with an emphasis on complex sterile injectable products, such as ready-to-use (RTU) products, and first-to-file or first-to-market opportunities that are difficult to formulate or manufacture or face complex legal and regulatory challenges. In the U.S., first-to-file products refer to generic products for which the Abbreviated New Drug Applications (ANDAs) containing patent challenges (or Paragraph IV certifications) to the corresponding branded products’ listed patents were the first to be filed with the FDA. In the U.S., manufacturers that launch first-to-file products, after success in litigating or otherwise resolving related patent challenges, and receive final FDA approval have the opportunity for 180 days of generic marketing exclusivity from competing generic products other than authorized generics. First-to-market products refer to products that are the first marketed generic equivalents of the corresponding branded products for reasons apart from statutory marketing exclusivity.
Products Overview
Branded Pharmaceuticals
Specialty Products Portfolio
The company commercializes a number of products within the market served by specialty distributors and specialty pharmacies and in which healthcare practitioners can purchase and bill payers directly (the buy and bill market). The company’s offerings primarily relate to the following areas: urology treatments, which focus mainly on PD and testosterone replacement therapies (TRT) for hypogonadism; orthopedics treatments, which focus on DC; and pediatric endocrinology treatments, which focus on central precocious puberty (CPP). Key product offerings in this portfolio include the following:
XIAFLEX, which is a non-surgical treatment for both DC (for adult patients with an abnormal buildup of collagen in the fingers that limits or disables hand function) and PD (for adult men with a collagen plaque and a penile curvature deformity of thirty degrees or greater at the start of therapy).
SUPPRELIN LA, which is a soft, flexible 12-month hydrogel implant based on the company’s hydrogel polymer technology that delivers histrelin acetate, a gonadotropin-releasing hormone agonist, and is indicated for the treatment of CPP in children.
AVEED, which is a novel, long-acting testosterone undecanoate for injection for the treatment of hypogonadism that is dosed only five times per year after the first month of therapy.
NASCOBAL Nasal Spray, which is a prescription nasal spray used as a supplement to treat vitamin B12 deficiency.
This portfolio has also included QWO (collagenase clostridium histolyticum-aaes), an injectable treatment for moderate to severe cellulite in the buttocks of adult women launched in March 2021. However, in December 2022, the company announced it would be ceasing the production and sale of QWO in light of market concerns about the extent and variability of bruising following initial treatment as well as the potential for prolonged skin discoloration.
Established Products Portfolio
This portfolio’s treatment offerings primarily relate to the following areas: pain management, including products in the opioid analgesics segment and for the treatment of pain associated with post-herpetic neuralgia, and urology, focusing mainly on the treatment of hypogonadism. Key product offerings in this portfolio include, among others, the following:
PERCOCET, which is an opioid analgesic approved for the treatment of moderate to moderately-severe pain.
TESTOPEL, which is a unique, long-acting implantable pellet indicated for TRT in conditions associated with a deficiency or absence of endogenous testosterone.
EDEX, which is a penile injection used to treat erectile dysfunction caused by conditions affecting nerves, blood vessels, emotions and/or a combination of factors.
The company’s pain products, including opioid products, are managed as mature brands and are not and have not been actively promoted for years. In December 2016, the company announced the elimination of its entire U.S. pain product field sales force.
Sterile Injectables
The Sterile Injectables segment includes a product portfolio of approximately 40 product families, including branded sterile injectable products that are protected by certain patent rights and has inherent scientific, regulatory, legal and technical complexities and generic injectable products that are difficult to formulate or manufacture or face complex legal and regulatory challenges. The company’s sterile injectables products are manufactured in sterile facilities in various dosage forms and are administered at hospitals, clinics and long-term care facilities. Key product offerings in this segment include, among others, the following:
VASOSTRICT, which is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. The company offers VASOSTRICT in multiple formulations, including the RTU pre-mix bottle it launched in February 2022.
ADRENALIN, which is a non-selective alpha and beta adrenergic agonist indicated for emergency treatment of certain allergic reactions, including anaphylaxis.
APLISOL, which is a sterile aqueous solution of a purified protein derivative for intradermal administration as an aid in the diagnosis of tuberculosis.
Ertapenem for injection (the authorized generic of Merck Sharp & Dohme Corp.’s (Merck) Invanz®), which is indicated for the treatment of certain moderate to severe infections.
Ephedrine sulfate injection, which is an alpha and beta adrenergic agonist and a norepinephrine-releasing agent indicated for the treatment of clinically important hypotension occurring in the setting of anesthesia.
Generic Pharmaceuticals
The Generic Pharmaceuticals segment includes a product portfolio of approximately 110 generic product families, including solid oral extended-release products, solid oral immediate-release products, liquids, semi-solids, patches (which are medicated adhesive patches designed to deliver the pharmaceutical through the skin), powders, ophthalmics (which are sterile pharmaceutical preparations administered for ocular conditions) and sprays and includes products that treat and manage a wide variety of medical conditions.
Generic products are the pharmaceutical and therapeutic equivalents of branded products and are generally sold under their generic (chemical) names rather than their brand names. Generic products are substantially the same as branded products in dosage form, safety, efficacy, route of administration, quality, performance characteristics and intended use, but are generally sold at prices below those of the corresponding branded products and thus represent cost-effective alternatives for consumers.
For example, in January 2021, the company launched lubiprostone capsules (the authorized generic of Mallinckrodt plc’s Amitiza).
International Pharmaceuticals
The company’s International Pharmaceuticals segment includes a variety of specialty pharmaceutical products, including over-the-counter (OTC) products, sold outside the U.S., primarily in Canada through its operating company Paladin Labs Inc. (Paladin).
Select Development Projects
XIAFLEX
XIAFLEX is approved by the FDA and marketed in the U.S. for the treatment of both DC and PD (two separate indications). In early 2020, the company announced that it had initiated its XIAFLEX development program for the treatment of plantar fibromatosis, for which it anticipates Phase 2 top-line data by the end of the first quarter of 2023. The company also initiated a proof-of-concept study in plantar fasciitis during the fourth quarter of 2022. The company may in the future develop its XIAFLEX product for potential additional indications, advancing its strategy of developing non-surgical orthopedic care interventions.
The company completed its acquisition of BioSpecifics Technologies Corp., a Delaware corporation and a commercial-stage biopharmaceutical company (BioSpecifics) in December 2020.
TLC599
In June 2022, the company announced that its subsidiary had entered into an agreement with Taiwan Liposome Company, Ltd. (TLC) to commercialize TLC599. TLC599 is an injectable compound in Phase 3 development for the treatment of osteoarthritis knee pain.
In September 2022, the company was informed by TLC of the top-line results from TLC’s Phase 3 clinical study to evaluate the efficacy and safety of TLC599 in patients with pain from osteoarthritis of the knee. While study participants treated with TLC599 showed improvement on the primary endpoint (change from baseline to week 12 on the WOMAC pain scale) consistent with the level of improvement reported in the previously conducted TLC599 Phase 2 clinical study, the difference compared to those receiving placebo was not statistically significant. Based on these data, it is evaluating options for TLC599 with TLC.
Other
The company’s remaining pipeline consists mainly of a variety of product candidates in its Sterile Injectables and Generic Pharmaceuticals segments. As of December 31, 2022, within these two segments, the company was actively pursuing approximately 70 product candidates, including approximately 30 ANDAs pending with the FDA, of which approximately 40% are associated with its Sterile Injectables segment, as well as approximately 40 additional projects in development, of which approximately 90% are associated with its Sterile Injectables segment, including RTU and other more differentiated product candidates.
The company expects to continue to focus investments in RTU and other product candidates in its Sterile Injectables segment, potentially including acquisitions and/or license and commercialization agreements, such as the 2022 Nevakar Agreement.
The company’s primary approach to developing generic products for these two segments is to target high-barrier-to-entry product opportunities, including first-to-file or first-to-market opportunities that are difficult to formulate or manufacture or face complex legal and regulatory challenges, as well as products that meet the evolving needs of hospitals and health systems. The company expects such product opportunities to result in products that are either the exclusive generic or have two or fewer generic competitors when launched, which it tends to lead to more sustainable market share and profitability for its product portfolio. In its Sterile Injectables business, the company also focuses on developing injectable products with inherent scientific, regulatory, legal and technical complexities, as well as developing other dosage forms and technologies.
The company periodically reviews its development projects in order to better direct investment toward those opportunities that it expects will deliver the greatest returns.
Strategy
The company focuses on driving long-term growth through a diversified and durable portfolio of businesses, continuing product development and manufacturing and commercialization excellence. The company’s strategic priorities include expanding and enhancing its portfolio with differentiated and durable products; reinventing how it works to better serve its customers, promote innovation and improve productivity; and being a force for good by embracing and adopting sustainable practices that benefit all of its stakeholders. Specific areas of management’s focus include:
Branded Pharmaceuticals: Accelerating performance of organic growth drivers in the company’s Specialty Products portfolio and expanding margin in its Established Products portfolio.
Sterile Injectables: Focusing on developing injectable products with inherent scientific, regulatory, legal and technical complexities, expanding the product portfolio to include other dosages and technologies and developing or acquiring high-barrier-to-entry products that are difficult to manufacture.
Generic Pharmaceuticals: Focusing on developing or acquiring high-barrier-to-entry products, including first-to-file or first-to-market opportunities that are difficult to formulate or manufacture or face complex legal and regulatory challenges.
Additionally, as part of the company’s Environmental, Social and Governance (ESG) strategy, it is committed to the adoption of more sustainable practices, including the promotion of Diversity, Equity and Inclusion (DE&I) in all that it does, and to operating its business in a responsible manner that seeks to minimize environmental impact, while promoting the safe, efficient and responsible use of global resources.
While its primary focus is on organic growth, the company plans to continue to evaluate and, where appropriate, execute on opportunities to expand through the licensing or acquisition of products or companies.
Major Customers
The company primarily sells its products to wholesalers, retail drug store chains, supermarket chains, mass merchandisers, distributors, mail order accounts, hospitals and/or government agencies. The company’s wholesalers and/or distributors purchase products from it and, in turn, supply products to retail drug store chains, independent pharmacies, hospitals, long-term care facilities, clinics, home infusion pharmacies, government facilities and managed care organizations (MCOs). The company’s current customer group reflects significant consolidation in recent years, marked by mergers and acquisitions and other alliances.
For the year ended December 31, 2022, the company’s customers included AmerisourceBergen Corporation (35%); McKesson Corporation (26%); and Cardinal Health, Inc. (20%). Some wholesalers and distributors have required pharmaceutical manufacturers, including the company, to enter into distribution service agreements (DSAs) pursuant to which the wholesalers and distributors provide pharmaceutical manufacturers with certain services, as well as certain information including, without limitation, periodic retail demand information, current inventory levels and other information. The company has entered into certain of these agreements.
Competition
Branded Pharmaceuticals
This segment’s major competitors, including Viatris Inc. (Viatris), Jazz Pharmaceuticals plc, Takeda Pharmaceutical Company Limited and Horizon Therapeutics Public Limited Company, among others, vary depending on therapeutic and product category, dosage strength and drug-delivery systems, among other factors.
Sterile Injectables
This segment’s major competitors, including Hospira, Inc. (a subsidiary of Pfizer Inc.), Fresenius Kabi USA, LLC, Viatris, Amphastar Pharmaceuticals, Inc., Amneal Pharmaceuticals, Inc. (Amneal), Hikma Pharmaceuticals PLC, Sandoz and Eagle Pharmaceuticals, Inc. (Eagle), among others, vary by product. A significant portion of the company’s sales, including sales to hospitals, clinics and long-term care facilities in the U.S., are controlled by a relatively small number of GPOs, including HealthTrust Purchasing Group, L.P., Premier Inc. and Vizient, Inc.
Generic Products
The company’s major competitors, including Teva Pharmaceutical Industries Limited, Viatris, Sandoz, Aurobindo Pharma Limited and Amneal, among others, vary by product.
Patents, Trademarks, Licenses and Proprietary Property
The company regards the protection of patents and other enforceable intellectual property rights that it owns or licenses as critical to its business and competitive position. Accordingly, the company relies on patent, trade secret and copyright law, as well as nondisclosure and other contractual arrangements, to protect its intellectual property. The company has a portfolio of patents and patent applications owned or licensed by it that cover aspects of its products. These patents and applications generally include claims directed to the compounds and/or methods of using the compounds, formulations of the compounds, pharmaceutical salt forms of the compounds or methods of manufacturing the compounds. The company’s policy is to pursue patent applications on inventions that are commercially important to the development and growth of its business.
As of February 27, 2023, the company held approximately: 152 U.S. issued patents, 45 U.S. patent applications pending, 427 foreign issued patents and 119 foreign patent applications pending. In addition, as of February 27, 2023, the company had licenses for approximately 73 U.S. issued patents, 14 U.S. patent applications pending, 167 foreign issued patents and 83 foreign patent applications pending. The company is seeking additional patent protection for several products, including XIAFLEX. The company may also obtain further patents or additional regulatory or patent exclusivity for one or more indications for any of its products in the future.
The company’s products are subject to different patent expiration dates. For example, the company’s patents related to NASCOBAL Nasal Spray expire in 2024, its patents related to AVEED expire in 2027 and its patents related to ADRENALIN expire in 2035.
XIAFLEX is a biological product. The company owns or has licensed rights to patents and patent applications related to XIAFLEX, including drug product and methods of manufacture patents and patent applications that will expire into the late 2030s and methods of use patents and patent applications for uses, such as plantar fibromatosis that will expire into the late 2030s/early 2040s.
The company’s patents provide protection by allowing it to exclude others from making, using, selling, offering for sale or importing that which is covered by the patent claims. For example, in August 2021, the U.S. District Court for the District of Delaware held that Eagle’s proposed vasopressin product did not infringe the company’s asserted patent claims related to VASOSTRICT. The expiration of a basic product patent or loss of patent protection resulting from a legal challenge typically results in significant competition from generic products or biosimilars against the originally patented product and can result in a significant reduction in revenues for that product in a very short period of time that may never be reversed.
Governmental Regulation
The company’s BLA-licensed products were licensed based on a determination by the FDA of safety, purity and potency as required under the Public Health Service Act (PHSA). Certain of the company’s subsidiaries sell products that are controlled substances as defined in the Controlled Substances Act and implementing regulations, which establish certain security and recordkeeping requirements administered by the U.S. Drug Enforcement Administration (DEA).
History
Endo International plc was founded in 1920. The company was incorporated in Ireland in 2013 as a private limited company and re-registered effective February 18, 2014 as a public limited company.
