United Therapeutics Corporation, a biotechnology company, focuses on the development and commercialization of innovative products to address the unmet medical needs of patients with chronic and life-threatening conditions.
The company builds on the strength of its research and development expertise and a distinctive, entrepreneurial culture that encourages innovation, creativity, inclusion, sustainability, and, simply, fun. The company has successfully obtained approval from the U.S. Food and D...
United Therapeutics Corporation, a biotechnology company, focuses on the development and commercialization of innovative products to address the unmet medical needs of patients with chronic and life-threatening conditions.
The company builds on the strength of its research and development expertise and a distinctive, entrepreneurial culture that encourages innovation, creativity, inclusion, sustainability, and, simply, fun. The company has successfully obtained approval from the U.S. Food and Drug Administration (FDA) for several medicines, is always conducting new clinical trials, and is working to create an unlimited supply of manufactured organs and organ alternatives for transplantation.
The company markets and sells the following commercial therapies in the United States to treat pulmonary arterial hypertension (PAH): Tyvaso DPI (treprostinil) Inhalation Powder (Tyvaso DPI); Tyvaso (treprostinil) Inhalation Solution (nebulized Tyvaso), which includes the Tyvaso Inhalation System; Remodulin (treprostinil) Injection (Remodulin); Orenitram (treprostinil) Extended-Release Tablets (Orenitram); and Adcirca (tadalafil) Tablets (Adcirca). Tyvaso DPI and nebulized Tyvaso are also approved to treat pulmonary hypertension associated with interstitial lung disease (PH-ILD). In the United States, the company markets and sells an oncology product, Unituxin (dinutuximab) Injection (Unituxin), which is approved for the treatment of high-risk neuroblastoma, and the Remunity Pump for Remodulin (Remunity). Outside the United States, the company derives revenues from sales of nebulized Tyvaso, Remodulin, and Unituxin.
The company is actively advancing a pipeline of research and development projects that includes new indications and delivery devices for its existing products, as well as new products to treat PAH and other conditions.
Products to Treat Pulmonary Hypertension
The company’s PH products were initially approved to treat only PAH. In March 2021, nebulized Tyvaso was approved to treat PH-ILD in addition to PAH. In May 2022, the company also obtained FDA approval of Tyvaso DPI to treat both PAH and PH-ILD. The company is engaged in further research and development of additional indications for nebulized Tyvaso to treat certain fibrotic lung conditions underlying PH-ILD.
Tyvaso DPI and Nebulized Tyvaso
Tyvaso was initially approved as a nebulized product by the FDA to treat PAH and was launched commercially in the United States in 2009. Following the successful INCREASE study of nebulized Tyvaso in patients with PH-ILD, including patients with underlying idiopathic pulmonary fibrosis (IPF) and combined pulmonary fibrosis and emphysema, the FDA approved its efficacy supplement to the nebulized Tyvaso New Drug Application (NDA) in March 2021. As a result, nebulized Tyvaso’s label was updated to include the PH-ILD indication. In May 2022, the FDA approved the company’s dry powder formulation of inhaled treprostinil called Tyvaso DPI, for the treatment of both PAH and PH-ILD. The company developed this product under an in-license from MannKind Corporation (MannKind) and launched this product commercially in the United States in June 2022.
The company sells Tyvaso DPI and nebulized Tyvaso to specialty pharmaceutical distributors in the United States. Nebulized Tyvaso is approved and commercialized in the United States, Israel, Argentina, the Dominican Republic, and Japan to treat PAH and PH-ILD, and is approved but not yet launched in additional countries in Latin America and Asia.
Tyvaso DPI is a drug-device combination product that incorporates the dry powder formulation technology and Dreamboat inhalation device technology used in MannKind’s Afrezza (insulin human) Inhalation Powder product, which was approved by the FDA in 2014 to treat patients with diabetes.
Nebulized Tyvaso is administered four times a day using its proprietary Tyvaso Inhalation System, which consists of an ultrasonic nebulizer and related accessories. Dose titration is achieved by varying the number of breaths per treatment session, typically starting at three breaths per session, and increasing the dose in three-breath increments during the titration process.
Remodulin
Remodulin was approved by the FDA for subcutaneous and intravenous administration in 2002 and 2004, respectively, and has been sold commercially in the United States since 2002. The company sells Remodulin to specialty pharmaceutical distributors in the United States and to pharmaceutical distributors internationally. Remodulin is indicated to treat patients with PAH to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with functional class II-IV (moderate to severe) symptoms. Outside of the United States, Remodulin is marketed and sold for the treatment of PAH throughout most of Europe, Canada, Mexico, and various countries throughout Asia, the Middle East, and Latin America.
Remunity Pump
In February 2021, the company launched limited commercial sales of the Remunity Pump, which is a semi-disposable system for subcutaneous delivery of treprostinil that it developed in collaboration with DEKA Research & Development Corp. (DEKA) under an exclusive development and license agreement. The Remunity Pump consists of a small, lightweight, durable pump and controller designed to have a service life of at least three years. The Remunity Pump uses disposable cassettes filled with Remodulin, which can be connected to the pump with less patient manipulation than is typically involved in filling other available subcutaneous pumps. In November 2019, the company entered into a supply agreement with an affiliate of DEKA to manufacture and supply the Remunity Pump to it. Under the terms of the agreement, the company reimburses all of DEKA’s and its affiliates’ costs to manufacture the Remunity Pump.
The Remunity Pump was initially made available to patients in weekly shipments of disposable cassettes that were pre-filled with Remodulin by the company’s specialty pharmacy distributors. In September 2022, the company launched a patient-filled version of the Remunity Pump, which enables patients to receive monthly shipments of empty, ready-to-fill Remunity cassettes and Remodulin. The majority of patients being treated with subcutaneous Remodulin in the United States are now using the Remunity Pump, and it is the only subcutaneous infusion system available in the United States for newly prescribed treprostinil patients. The Remunity Pump is classified by CMS as durable medical equipment.
In January 2025, DEKA obtained FDA clearance of a new version of the Remunity Pump, which is intended to improve the patient experience by making the pump easier to use and will be offered only as a patient-filled device. The company plans to launch this new system, called RemunityPRO, later this year.
Orenitram
Orenitram is the only FDA-approved, orally-administered prostacyclin analogue, and is the only oral PAH prostacyclin class therapy approved in the United States that is titratable to a maximum tolerated dose without a dose ceiling. The company sells Orenitram to the same specialty pharmaceutical distributors in the United States that distribute Tyvaso DPI, nebulized Tyvaso, and Remodulin. In 2013, the FDA approved Orenitram for the treatment of PAH patients to improve exercise capacity. The primary study that supported the efficacy of Orenitram was a 12-week monotherapy study in which PAH patients were not on any approved background PAH therapy. In August 2018, the company announced that its clinical study of Orenitram called FREEDOM-EV had met its primary endpoint of delayed time to first clinical worsening event. In particular, the preliminary results showed that Orenitram, when taken with an oral PAH background therapy, decreased the risk of a clinical worsening event versus placebo by 25 percent (p=0.0391), driven by a 61 percent decrease in the risk of disease progression for patients taking Orenitram, when compared to placebo (p=0.0002). In October 2019, the FDA approved a supplement to the Orenitram NDA to update the product’s label to reflect the FREEDOM-EV results. As a result, Orenitram is indicated to delay disease progression and improve exercise capacity.
Adcirca
Adcirca is a PDE-5 inhibitor, the active pharmaceutical ingredient of which is tadalafil. Tadalafil is also the active pharmaceutical ingredient in Cialis, which is marketed by Eli Lilly and Company (Lilly) for the treatment of erectile dysfunction.
Product to Treat Cancer — Unituxin
In March 2015, the FDA approved the company’s Biologics License Application (BLA) for Unituxin, in combination with granulocyte-macrophage colony-stimulating factor, interleukin-2, and 13-cis-retinoic acid, for the treatment of patients with high-risk neuroblastoma (a rare form of pediatric cancer) who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Unituxin is a chimeric monoclonal antibody composed of a combination of mouse and human DNA that induces antibody-dependent cell-mediated cytotoxicity, a mechanism of cell-mediated immunity whereby the immune system actively targets a cell that has been bound by specific antibodies. Unituxin therapy is associated with severe side effects, including infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome. Unituxin has also been approved in Canada and Japan.
Research and Development
The company focuses its research and development efforts on the following pipeline programs. The company also engages in a variety of additional research and development efforts, including efforts to develop new and improved devices to deliver its current commercial products, and technologies designed to increase the supply of transplantable organs and organ alternatives and improve outcomes for transplant recipients through xenotransplantation, regenerative medicine, bio-artificial organ alternatives, three-dimensional (3D) bioprinting of organ alternatives, and ex vivo lung perfusion.
Nebulized Tyvaso — TETON studies
The company is conducting two phase 3 studies of nebulized Tyvaso, called TETON 1 and TETON 2, in patients with idiopathic pulmonary fibrosis (IPF). TETON 1 is being conducted in the United States and Canada, and TETON 2 is being conducted outside the United States and Canada. Enrollment in the TETON 2 study was completed in July 2024, after enrolling a total of 597 patients, and TETON 1 completed enrollment in January 2025 with 598 patients. The company is also conducting a phase 3 study of nebulized Tyvaso called TETON PPF for the treatment of progressive pulmonary fibrosis (PPF); the first patient in TETON PPF was enrolled in October 2023. The primary endpoint of each TETON study is the change in absolute forced vital capacity (FVC) from baseline to week 52.
Both the FDA and the European Medicines Agency (EMA) have granted orphan designation for treprostinil to treat IPF. The FDA denied the company’s orphan designation application for PPF. If the TETON studies are successful, the company plans to seek FDA approval to expand the nebulized Tyvaso label to include IPF and PPF. The company also plans to seek FDA approval to expand the Tyvaso DPI label to include IPF and PPF, following completion of any FDA-required bridging studies.
Ralinepag
Ralinepag is a next-generation, once-daily, oral, selective, and potent prostacyclin receptor agonist that the company is developing for the treatment of PAH. The company is enrolling ADVANCE OUTCOMES, which is a phase 3, event-driven study of an extended-release formulation of ralinepag in PAH patients with a primary endpoint of time to first clinical worsening event. ADVANCE OUTCOMES is a global, multi-center, placebo-controlled trial that includes patients on approved oral background PAH therapies. During the first quarter of 2023, the company discontinued a separate phase 3 study of ralinepag called ADVANCE CAPACITY, due to slow enrollment and a redirection of the company’s internal resources toward the TETON PPF study. In October 2023, the data monitoring committee for the ADVANCE OUTCOMES study completed a routine, unblinded safety review of data from nearly 510 patients enrolled in the study, and unanimously recommended continuation of the trial without modification. The study is targeting enrollment of approximately 700 patients. The company plans to close enrollment in mid-2025 and accrue clinical worsening events through the end of 2025.
Manufactured Organs and Organ Alternatives
Xenotransplantation
The company’s xenotransplantation program includes three development-stage organ products known as ‘xenografts’, which are intended to be transplanted from gene-edited pigs into humans.
The UKidney is a development-stage kidney from a pig with ten gene edits to support organ functioning in the human body. Six human genes were added to the pig genome to facilitate immune acceptance of the organ, while four genes were inactivated: three that contribute to porcine organ rejection in humans and one that can cause organ growth beyond what is normal for humans. The UHeart is a heart from the same pig with ten gene edits.
The UThymoKidney is a development-stage kidney from a pig with a single gene edit, together with tissue from the pig’s thymus. The pig’s thymus tissue is intended to condition the recipient’s immune system to recognize the UThymoKidney as ‘self’ and reduce the likelihood of rejection. The single gene that is disrupted in the pig is responsible for the synthesis of alpha-gal, a sugar on the surface of cells that can cause immediate rejection of a porcine organ when transplanted into the human body. Because tissues from pigs containing this gene edit do not contain detectable levels of the alpha-gal sugar, the company refers to materials derived from this pig as GalSafe. In December 2020, the GalSafe pig was approved by the FDA for use as human food and as a potential source for biomedical purposes. Meat from GalSafe pigs is currently being produced for individuals with alpha-gal syndrome, an allergy to meat caused by a bite from the lone star tick. This approval marked only the second FDA approval of a gene-edited animal as a source of food, and the first such approval for a mammal.
The company has entered into agreements with Johns Hopkins University (JHU), New York University (NYU), the University of Alabama at Birmingham (UAB), and the University of Maryland, Baltimore (UMB) to perform preclinical testing of its porcine xenografts, with the goal of commencing human clinical trials in the near term. These collaborations have been generating data regarding its UHearts, UKidneys, and UThymoKidneys. In addition to evaluating its xenografts in animal models, the company’s research efforts have used innovative preclinical human models to obtain insights into how xenografts function inside the human body.
In December 2024, the company submitted an Investigational New Drug application (IND) to the FDA related to its UKidney product. In January 2025, the FDA cleared this IND, which enables the company to commence a clinical trial. This study is expected to enroll an initial cohort of six end-stage renal disease (ESRD) patients, expanding to up to 50 participants, and the company intends for this study to support a Biologics License Application (BLA) with the FDA. This study is designed as a combination phase 1/2/3 trial (sometimes referred to as a ‘phaseless’ study) to evaluate safety and efficacy seamlessly without moving through separate phase 1, phase 2, and phase 3 studies that are typically associated with conventional drug approvals.
In February 2024, the company inaugurated a clinical-scale, designated pathogen-free (DPF) facility in Virginia and began populating the facility with animals during the first quarter of 2024. The company expects this DPF to supply xenografts compliant with FDA current Good Manufacturing Practices (cGMP) for human clinical trials, with a target capacity of up to 125 organs per year.
Regenerative Medicine, Bio-Artificial Organ Alternatives, and 3D Bioprinting of Organ Alternatives
Miromatrix: In December 2023, the company acquired Miromatrix Medical Inc. (Miromatrix), a company based in Minnesota focused on the development of new technologies for generating manufactured kidneys and liver alternatives composed of human primary cells. The Miromatrix external liver assist product, called miroliverELAP, uses a decellularized porcine liver matrix that has been seeded with human-derived cells and an extracorporeal blood circuit to maintain liver support in patients experiencing acute liver failure. Miromatrix first used its decellularization technology to successfully develop two acellular products, MiroMesh and MiroDerm, which received FDA 510(k) clearance for hernia repair and wound care applications, respectively, and which were later spun off by Miromatrix. In October 2024, Miromatrix initiated screening of patients for a phase 1 study of miroliverELAP in patients with acute liver failure, which is the first human clinical trial of a manufactured organ alternative. Miromatrix is also developing miroliver, a fully implantable manufactured liver alternative product, and mirokidney, a fully implantable manufactured kidney alternative product, both of which are based on decellularized porcine organ scaffolds that have been reseeded with human-derived cells. Initially, the Miromatrix products are intended to be allogeneic, requiring the use of standard immunosuppression protocols.
ULobe: The ULobe is a development-stage engineered lung lobe alternative made using a porcine lung scaffold that is decellularized and then re-cellularized with cells from a human donor other than the recipient (also called ‘allogeneic’ cells). In 2023, the company’s Regenerative Medicine Laboratory in Research Triangle Park, North Carolina (RTP) produced 450 decellularized lung scaffolds, 220 recellularized lungs, and 1.7 trillion human cells for use in recellularization.
ULung: The ULung is a development-stage engineered lung alternative composed of a 3D printed lung scaffold cellularized with either allogeneic human lung cells, or the patient’s own cells (known as ‘autologous’ cells), with the goal of reducing or eliminating the need for immunosuppression. The lung scaffold used in the ULung is printed using 3D printers being developed in collaboration with 3D Systems, Inc. The company’s Organ Manufacturing Group, located in Manchester, New Hampshire, has achieved recognition for developing the world’s most complex 3D printed object. Its lung scaffold designs consist of a record 44 trillion voxels that lay out 4,000 kilometers of pulmonary capillaries and 200 million alveoli, which demonstrate gas exchange in preclinical models. Under the company’s agreement with 3D Systems, it also has the exclusive right to develop additional human solid organ alternatives using 3D Systems’ printing technology.
IVIVA: In October 2023, the company completed the acquisition of IVIVA Medical, Inc. (IVIVA), a preclinical stage company based in Massachusetts, focused on bio-artificial manufactured kidney alternative products. IVIVA’s preclinical implantable kidney alternative product uses autologous cells to mimic important physiological functions of native kidneys in recipients to support their native kidney function without the need for immunosuppression. The product is designed to replace the need for external kidney dialysis.
Ex Vivo Lung Perfusion
The company’s ex vivo lung perfusion (EVLP) program uses the first FDA-approved acellular EVLP technology on the market, the XVIVO Perfusion System (XPS) with Steen Solution Perfusate, to offer the only commercially-available centralized EVLP service in the United States. EVLP technology increases the number of transplantable lungs by giving surgeons the ability to assess the function of lungs to determine if the lungs are suitable for transplantation. This allows for the transplantation of lungs that would have otherwise not been transplanted. Centralized EVLP services make EVLP available to small and large transplant centers and remove barriers to the transplantation process to optimize organ utilization and increase the supply of transplantable lungs.
The company’s wholly-owned subsidiary, Lung Bioengineering Inc., provides commercial EVLP services on a fee-for-service basis to transplant centers through dedicated facilities located in Silver Spring, Maryland, and Jacksonville, Florida, using the XPS System. In 2024, Lung Bioengineering completed a registrational study of another centralized EVLP technology called the Centralized Lung Evaluation System (CLES) and submitted a premarket approval application to the FDA in September 2024 for commercial approval of CLES, which has been accepted by the FDA.
Sustainable Delivery of Organs and Organ Alternatives
Together with the company’s work on therapeutic interventions, it is working with third parties to develop scalable technologies to efficiently deliver an unlimited supply of manufactured organs and organ alternatives to transplant centers and waiting patients, while minimizing environmental impact. The company’s organ delivery research efforts are focused on the development of piloted and autonomous electric vertical take-off and landing aircraft systems to quickly, reliably, and sustainably deliver organs and organ alternatives from manufacturing facilities to transplant centers.
Beginning in 2017, the company entered into a series of agreements with BETA Technologies, Inc. to support the development of all-electric aircraft to help it meet its future distribution requirements for manufactured organs and organ alternatives. In October 2021, the company successfully completed the first-ever drone delivery of a human lung for transplant at Toronto General Hospital, demonstrating the feasibility of the company’s goal of delivering its manufactured organs and organ alternatives with zero carbon footprint aircraft. In October 2024, the company entered into a collaboration agreement with Robinson Helicopter Company to support its efforts to develop and certify zero-emission, hydrogen-powered helicopters based on Robinson’s R44 and R66 helicopter models.
Sales and Marketing
The company’s marketing strategy for its commercial PAH and PH-ILD products is to use its sales and marketing teams to reach out to the prescriber community to: increase PAH and PH-ILD awareness; increase understanding of the progressive nature of PAH and the importance of early treatment; communicate the increased risks when ILD patients develop PH-ILD; and increase awareness of its commercial products and how they fit into the various stages of disease progression and treatment.
Distribution of Commercial Products
United States Distribution of Tyvaso DPI, Nebulized Tyvaso, Remodulin, Remunity Pump, Orenitram, and Unituxin
The company distributes Tyvaso DPI, nebulized Tyvaso, Remodulin, the Remunity Pump, and Orenitram throughout the United States through two contracted specialty pharmaceutical distributors: Accredo Health Group, Inc. and its affiliates (Accredo), and Caremark, L.L.C. (CVS Specialty). These distributors are required to maintain certain minimum inventory levels to facilitate an uninterrupted supply to patients who are prescribed its therapies. The company compensates Accredo and CVS Specialty on a fee-for-service basis for certain ancillary services in connection with the distribution of these products.
Under the company’s distribution agreements, it sells each of its treprostinil-based products to these distributors. The company has also established patient assistance programs in the United States, which provide its treprostinil-based products to eligible uninsured or under-insured patients at no charge. Accredo and CVS Specialty assist the company with the administration of these programs.
The company distributes Unituxin throughout the United States through an exclusive distribution agreement with ASD Specialty Healthcare, Inc. (ASD), an affiliate of Cencora, Inc. (formerly known as AmerisourceBergen Corporation).
The United States Distribution of Adcirca
Under the company’s manufacturing and supply agreement with Lilly, Lilly manufactures and distributes Adcirca on its behalf through its wholesaler network in the same manner that it distributes its own pharmaceutical products. Under the terms of this agreement, the company takes title to Adcirca upon completion of its manufacture by Lilly. Adcirca is shipped to customers in accordance with purchase orders received by Lilly.
International Distribution of Tyvaso DPI, Nebulized Tyvaso, Remodulin, Orenitram, and Unituxin
The company sells Remodulin outside the United States to various distributors, each of which has exclusive distribution rights in one or more countries within Europe, the Middle East, Asia, and South and Central America. The company’s primary distributor outside the United States is Grupo Ferrer Internacional, S.A. (Ferrer), which holds Remodulin marketing authorization rights in many of these territories. The company sells nebulized Tyvaso commercially to distributors that have exclusive distribution rights in Argentina and Israel. The company also sells nebulized Tyvaso exclusively through Mochida Pharmaceutical Co., Ltd. (Mochida), in Japan, where the product was approved to treat PAH in late 2022, and to treat PH-ILD in 2024. In 2024, the company also granted Japanese distribution rights for Tyvaso DPI to Mochida, which plans to seek marketing authorization in Japan. The company also distributes Remodulin and Unituxin in Canada through a specialty pharmaceutical wholesaler. In some of the markets where the company is not licensed to market Remodulin, Remodulin is available, but not marketed, on a named patient basis in which therapies are approved for individual patients by a national medical review board, hospital, or health plan on a case-by-case basis. Similar named-patient programs are also available for nebulized Tyvaso in certain countries. The company plans to revisit seeking EMA approval for nebulized Tyvaso if the TETON program is successful. In December 2023, the U.K. Medicines and Healthcare products Regulatory Authority (MHRA) provided positive feedback to Ferrer indicating that the INCREASE study and data from its open label extension could support a marketing authorization application (MAA) for nebulized Tyvaso to treat PH-ILD without further clinical studies. In late 2024, MHRA agreed to also consider the submission package from Mochida’s recent approval of nebulized Tyvaso for PH-ILD in Japan as supporting evidence through the International Recognition Procedure. As a result, Ferrer plans to submit an MAA to the MHRA in 2025. The company distributes Unituxin in Japan exclusively through Ohara Pharmaceutical Co., Ltd., which obtained Japanese marketing authorization during the second quarter of 2021.
Patents and Other Proprietary Rights, Strategic Licenses, and Market Exclusivity
Tyvaso DPI, Nebulized Tyvaso, Remodulin, and Orenitram Proprietary Rights
The company has issued patents and pending patent applications covering its treprostinil-based products, Tyvaso DPI, nebulized Tyvaso, Remodulin, and Orenitram. The company has two unexpired patents related to the manufacture of treprostinil that expire in 2028 and are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book, for Tyvaso DPI, nebulized Tyvaso, Remodulin, and Orenitram.
In addition to the treprostinil patents, the company has other patents specific to its individual treprostinil-based products, including the following:
Tyvaso DPI: The company has three Orange Book-listed U.S. patents that it licenses from MannKind directed to the composition of Tyvaso DPI drug product, which expire in 2025, 2030, and 2035, respectively. The company has another issued U.S. patent listed in the Orange Book directed to a method of improving exercise capacity in patients with PH-ILD expiring in 2042. Additionally, the company’s license agreement with MannKind includes rights to a substantial portfolio of additional issued U.S. patents related to a component of the drug product and methods of making the drug product, which expire at various dates through 2035, and pending applications that, if issued, could provide protection to 2042 or beyond.
Nebulized Tyvaso: The company has been granted two U.S. patents directed to a method of treating pulmonary hypertension and a kit for treating pulmonary hypertension. These two patents expire in 2028. The company has also been granted a patent on methods of treating pulmonary hypertension by administering treprostinil by inhalation, which expires in 2027. This patent is also listed in the Orange Book. Additionally, the company has been granted a patent directed to a method of improving exercise capacity in PH-ILD patients, which expires in 2042.
Remodulin: The company has been granted three U.S. patents covering an improved diluent for Remodulin, which expire in 2028 and 2029. All three of these patents are listed in the Orange Book.
Orenitram: The company’s U.S. patents for Orenitram orally administered formulations, controlled moisture storage and manufacturing methods, as well as those covering controlled release formulations licensed to it by Supernus Pharmaceuticals Inc. (Supernus). These patents will expire in the United States between 2026 and 2031.
The company has international counterparts to many of the patents and additional pending U.S. and international patent applications related to Tyvaso DPI, nebulized Tyvaso, Remodulin, and Orenitram.
Regulatory Exclusivity
Tyvaso DPI and Nebulized Tyvaso: In 2010, the FDA granted orphan drug designation for Tyvaso, which resulted in an orphan exclusivity period that expired in July 2016. In March 2021, the FDA granted three-year clinical trial exclusivity for PH-ILD as a result of the INCREASE study and the expansion of the nebulized Tyvaso label to include a PH-ILD indication. This exclusivity period covered both nebulized Tyvaso and Tyvaso DPI for PH-ILD, and expired in March 2024. Additionally, the FDA determined in August 2024 that the company is entitled to a period of exclusivity for nebulized Tyvaso and Tyvaso DPI based on a clinical trial conducted to obtain approval for a PH-ILD indication, and that this exclusivity expires on May 23, 2025. In 2004, the European Commission designated nebulized Tyvaso an orphan medicinal product for the treatment of both PAH and chronic thromboembolic pulmonary hypertension, which would confer a ten-year exclusivity period commencing if and when the company obtains marketing approval. In December 2020, the FDA granted orphan designation for treprostinil for the treatment of IPF.
Remodulin: Regulatory exclusivity for Remodulin in the United States and Europe has expired.
Orenitram: In November 2019, following approval of the company’s supplemental NDA to reflect the FREEDOM-EV results in the Orenitram label, the FDA granted orphan exclusivity for the new indication that Orenitram delays disease progression in PAH patients. This exclusivity expires in October 2026.
Supernus License
In 2006, the company entered into an exclusive license agreement with Supernus to use certain of its technologies in manufacturing Orenitram.
Manufactured Organ and Organ Alternative Proprietary Rights
The company has over 150 pending patent applications and multiple issued patents covering various aspects of its 3D organ alternative bioprinting program, and it has exclusively licensed an extensive 3D printing patent portfolio from 3D Systems for use in the field of manufacturing solid organ alternatives. The company’s xenotransplantation patent portfolio includes over 150 pending applications and issued patents, including nearly one hundred issued patents in the U.S. and abroad. The company’s regenerative medicine patent portfolio, including its newly-acquired Miromatrix and IVIVA programs, includes over 300 pending applications and issued patents.
Adcirca License Agreement
In 2008, Lilly granted the company an exclusive license to develop, market, promote, and commercialize Adcirca for the treatment of pulmonary hypertension in the United States. The company agreed to pay Lilly royalties based on its net product sales of Adcirca. Lilly retained the exclusive rights to develop, manufacture, and commercialize pharmaceutical products containing tadalafil, the active pharmaceutical ingredient in Adcirca, for the treatment of pulmonary hypertension outside of the United States and for the treatment of other diseases worldwide. Lilly retained authority for all regulatory activities with respect to Adcirca and for setting the wholesale price of Adcirca. The current term of the company’s Adcirca license agreement expires December 31, 2026.
Unituxin Proprietary Rights and Regulatory Exclusivity
Approval of the company’s BLA for Unituxin conferred a 12-year data exclusivity period through March 2027, during which the FDA may not approve a biosimilar for Unituxin. The company’s orphan drug exclusivity in the United States for Unituxin expired in March 2022.
DEKA Agreements
In December 2014, the company entered into an exclusive agreement with DEKA to develop a semi-disposable system for subcutaneous delivery of Remodulin, which it refers to as the Remunity Pump. The company’s agreement with DEKA expires on the last to occur of 25 years from the first product launch under the agreement, or upon the expiration of the last valid claim of a patent licensed from DEKA under the agreement that covers the Remunity Pump. Remunity and RemunityPRO are covered by issued patents and pending patent applications both in the U.S. and other countries. The expiration dates of issued U.S. patents range from 2027 through 2033.
Tyvaso DPI and the MannKind Agreement
In September 2018, the company entered into a worldwide, exclusive license and collaboration agreement with MannKind for the development and commercialization of Tyvaso DPI for the treatment of PAH. The agreement became effective on October 15, 2018.
Under the company’s agreement with MannKind, it is responsible for global development, regulatory, and commercial activities related to Tyvaso DPI, and it shares manufacturing responsibilities with MannKind.
In December 2023, MannKind entered into a royalty purchase agreement with Sagard Healthcare Funding Partners Borrowers 2 SPE, LP, with the company’s consent, to sell ten percent of the royalties payable under the license agreement (i.e., one percentage point of the ten percent royalty).
Under the company’s license agreement with MannKind, it has an exclusive license to a variety of granted and pending patents and patent applications related to treprostinil inhalation powder and the Dreamboat device, including multiple patent families covering the U.S. and other major market countries. These patents cover drug formulation, devices and device components, and manufacturing processes and intermediates. In August 2021, the company entered into a commercial supply agreement with MannKind (as amended, the Supply Agreement).
Ralinepag and the Arena Agreement
On November 15, 2018, the company entered into an exclusive license agreement with Arena Pharmaceuticals, Inc. (Arena) related to ralinepag. On January 24, 2019, in connection with the closing of the transactions contemplated by the license agreement, Arena granted to the company perpetual, irrevocable, and exclusive rights throughout the universe to develop, manufacture, and commercialize ralinepag; Arena transferred to the company certain other assets related to ralinepag, including, among others, related domain names and trademarks, permits, certain contracts, inventory, regulatory documentation, Investigational New Drug (IND) Application No. 109021 (related to ralinepag), and non-clinical, preclinical, and clinical trial data; the company assumed certain limited liabilities from Arena, including among others, all obligations arising after the closing under the assumed contracts and the IND.
Other
The company is party to various other license agreements related to therapies and technologies under development.
Manufacturing and Supply
The company relies on Minnetronix Inc. and Phillips-Medisize Corp. to manufacture the nebulizer used in its Tyvaso Inhalation System and various third parties to manufacture the monthly disposable device accessories for the Tyvaso Inhalation System. The company relies entirely on Lilly to manufacture Adcirca.
Governmental Regulation
The company is required to report its 340B ceiling prices to the Health Resources and Services Administration (HRSA) on a quarterly basis, which HRSA then publishes to 340B covered entities.
In order to be eligible to have the company’s products paid for with federal funds under Medicaid and Medicare Part B and purchased by certain federal agencies and grantees, the company also participates in the U.S. Department of Veterans Affairs (VA) Federal Supply Schedule (FSS) pricing program.
The company is also subject to numerous other anti-bribery and anti-fraud laws, including the U.S. Foreign Corrupt Practices Act, the UK Bribery Act, and the federal Civil Monetary Penalties Law.
In addition, the company is required to comply with the California Consumer Privacy Act (CCPA).
History
United Therapeutics Corporation was founded in 1996. The company was incorporated in Delaware in 1996.
