Amphastar Pharmaceuticals Profile
Amphastar Pharmaceuticals, Inc. operates as a bio-pharmaceutical company.
The company is focusing primarily on developing, manufacturing, marketing, and selling technically challenging generic and proprietary injectable, inhalation, and intranasal products, as well as insulin active pharmaceutical ingredient, or insulin API products. The company manufactures and sells over 25 products, the overwhelming majority of which are prescription pharmaceuticals. Since December 2018, the company has sold its patented Primatene MIST using a new hydrofluoroalkanes, or HFA, formulation as the company's sole over-the-counter product.
The company's largest products by net revenues include BAQSIMI glucagon nasal powder, or BAQSIMI, Primatene MIST, glucagon, epinephrine, phytonadione, and lidocaine. In April 2022, the FDA approved the company's ganirelix acetate injection 250mg/0.5mL prefilled syringe, which the company launched in June 2022. In July 2022, the FDA approved the company's vasopressin injection, USP 20 Units/mL, 1 mL single-dose vial, which the company launched in August 2022. In May 2022, the FDA approved the company's regadenoson injection, 0.08mg/mL, 5mL, single-dose prefilled syringe, which the company launched in April 2023.
In March 2023, the FDA approved the company's naloxone hydrochloride nasal spray 4mg, REXTOVY, which the company plans to launch in the first quarter of 2024. In June 2023, the company completed its acquisition of BAQSIMI, the first and only nasally administered glucagon for the treatment of severe hypoglycemia in people with diabetes, and is available in 27 international markets.
The company is developing a portfolio of generic abbreviated new drug applications, or ANDAs, biosimilar insulin product candidates and proprietary product candidates, which are in various stages of development and target a variety of indications. Four of the ANDAs and one of the biosimilar insulin candidates are on file with the FDA.
The company's multiple technological capabilities enable the development of technically challenging products with limited competition. These capabilities include characterizing complex molecules, analyzing and synthesizing peptides and proteins, conducting immunogenicity studies, engineering particles, and improving drug delivery through sustained-release technology. These technological capabilities have enabled the company to produce bioequivalent versions of complex drugs and support the development and manufacture of a broad range of dosage formulations, including solutions, emulsions, suspensions, and lyophilized products, as well as products administered via pre-filled syringes, vials, nasal sprays, metered-dose inhalers, or MDIs, and dry powder inhalers, or DPIs.
The company's primary strategic focus is developing and commercializing products with high technical barriers to market entry. The company is specifically focused on products that:
Leverage the company's proprietary research and development capabilities;
Require raw materials or APIs for which the company has a competitive advantage in sourcing, synthesizing, or manufacturing; and/or
Improve upon an existing drug's formulation with respect to drug delivery, safety, and/or efficacy.
The company has made several strategic acquisitions of companies, products, and technologies to complement the company's internal growth and expertise. These acquisitions have strengthened the company's core injectable and inhalation product technology infrastructure by providing additional manufacturing, marketing, and research and development capabilities, including the ability to manufacture starting materials, API, and other product components.
Markets
The company primarily targets products with high technical barriers to market entry, with a particular focus on the injectable and inhalation markets. The company also manufactures and sells certain APIs.
Injectable Market. The company's generic development, including interchangeable biosimilar portfolio is targeting opportunities in over $11 billion of this market. The injectable market requires highly technical manufacturing capabilities and compliance with strict current Good Manufacturing Practice, or cGMP, requirements, which create high barriers to market entry. Due to these high barriers to market entry, there are a limited number of companies with the technology and experience needed to manufacture injectable products. There have also been a number of quality issues over the past several years that have disrupted the ability of certain injectable manufacturers to produce sufficient product quantity to meet market demand. As such, the supply of injectables has been constrained, even as demand for injectable products has continued to increase.
Inhalation Market. The company's generic development portfolio is targeting opportunities in over $6 billion of this market. Inhalation drug therapy is used extensively to treat respiratory conditions such as asthma and chronic obstructive pulmonary disease. The MDI is the most widely used device to deliver inhalation therapies. It uses pressurized gas, historically chlorofluorocarbons, or CFCs, and more recently HFAs, to release its dose when the patient activates the device. The DPI, which does not rely on a propellant, is also widely used. As in the case of injectables, there are significant technical barriers to manufacturing inhalation products. The evolution of inhalation delivery technologies from nebulizers and CFCs to HFAs and DPIs has required manufacturers of inhalation products to re-formulate their products, which in many cases may require technical engineering capabilities, additional regulatory approvals and modified delivery devices. Additionally, the development of generic HFA and DPI products requires bioequivalence studies for FDA approval.
Strategy
The company is pursuing the following key strategies: diversifying the company's revenues by commercializing its product candidates; focusing on complex generic product opportunities; developing proprietary products; leveraging the company's vertically integrated infrastructure to drive operational efficiencies; and targeting and integrating the acquisitions of pharmaceutical companies, products, and technologies.
Technical Capabilities
The company develops, manufactures, markets, and selsl generic and proprietary products that utilize injectable, inhalation, and intranasal delivery systems. The company also manufactures and sells insulin API.
Injectable. The company's injectable product technologies enable the company to develop and manufacture generic and proprietary injectables in liquid, lyophilized, suspension, and emulsion forms, as well as the use of pre-filled syringes to facilitate safety and convenience to users. The company has multiple injectable manufacturing facilities that include aseptic filling lines dedicated to the sterile production of injectable products. Additionally, the company maintains compliance with cGMP regulations, which has enabled the company to obtain regulatory approvals and support commercial supply.
Inhalation and Intranasal. The company is focused on developing a broad range of generic and proprietary inhalation and intranasal products utilizing various delivery technologies. The company has expertise in formulating HFA-based MDIs and DPIs, as well as packaging the company's inhalation drugs in blister packs and other forms which can be used for loading the company's products into a variety of inhalation devices. As with the company's injectable products, the company maintains compliance with cGMP regulations, which will enable the company to obtain regulatory approvals and support commercial supply. Additionally, the company has extensive formulation and clinical experience in developing complex formulations that can be administered by intranasal delivery.
The company has advanced capabilities that enable the company to develop technically challenging products.
Characterization of complex molecules. Complex molecule characterization includes determining physicochemical properties, biological activity, immunochemical properties, and purity. Such characterization is important in developing a generic product that is considered the same as a reference drug product, which in turn allows the generic drug developer to demonstrate such 'sameness' to the FDA, which ultimately allows for interchangeability with the reference drug product. Complex drugs typically have large molecules composed of a mixture of molecules that differ very slightly from one another. These slight variances make such complex molecules difficult to characterize. The company has developed analytical tools that have enabled the company to characterize complex molecules in the company's products and product candidates. The company has the technology to develop a variety of additional analytical tools that will enable the company to characterize other complex molecules, including peptide and protein-based products.
Immunogenicity. The ability of an antigen to elicit immune responses is called immunogenicity. Unwanted immunogenicity, which is strongly linked with peptide and protein drug products, occurs when a patient mounts an undesired immune response against drug therapy. As a result, the FDA has signaled that they may require immunogenicity studies as part of the new pathway for biosimilars and biogenerics. In the past, the FDA has required these studies to approve products with complex molecules. The company has gained expertise in immunogenicity by performing immunogenicity studies in connection with the FDA approval process for the company's enoxaparin product. The company's experience conducting these complex immunogenicity studies will be of primary importance in the company's future efforts to develop complex molecules, biosimilar, and biogeneric product candidates.
Peptide and protein product development and production. The development of peptide and protein drug products utilizes the company's characterization technology, immunogenicity studies, synthetic capabilities, recombinant DNA, or rDNA, and API manufacturing technology. The company has experience using rDNA manufacturing technology, including the genetic engineering of host cells, fermentation to promote cell culture growth, and isolation and purification of the desired protein from the cell culture. Testing is required to ensure that only the desired protein is included in the finished product through each step. This technology will allow the company to develop protein and peptide drug products. In December 2020, the company received the first-ever FDA approval for a generic version of Glucagon for Injection Emergency Kit. The FDA determined the company's approved peptide product to be bioequivalent and therapeutically equivalent to the reference listed drug, which has rDNA origin.
Particle engineering. Particle engineering is important in the field of pulmonary drug delivery as there is a direct relationship between the properties of a particle and its absorption by the lungs. The company's expertise and technology, which applies to particle engineering and physical chemistry, allow the company to engineer particles' size, shape, surface smoothness and distribution to develop inhalation products that are more easily dispersed through targeted areas. This expertise will allow the company to formulate difficult- to-disperse inhalation products and demonstrate the sameness of the reference-listed drugs to the FDA.
Sustained-release. The company has developed technology to improve drug delivery through sustained-release injectable products. The company's sustained-release technology aims to create products that require less dosing frequency, which can lead to diminishing fluctuations of drug concentrations in a patient's bloodstream that would otherwise require more frequent dosing. The company plans to use its sustained-release technology to develop generic and proprietary products.
Novel formulation. The company has the capability to develop novel formulations to enhance drug delivery. For certain intranasal medications, novel formulations might be required to increase the drug's absorption rate to deliver the medication safely and efficiently. The company plans to use its novel formulation with the company's intranasal epinephrine and other proprietary products.
Finished Pharmaceutical Products
Marketed Products
The company manufactures and sells over 25 products in the company's finished pharmaceutical product segment. The following is a description of products in the company's existing portfolio.
BAQSIMI (glucagon) nasal powder 3mg
BAQSIMI a dry nasal spray used in an emergency for the treatment of severe hypoglycemia in people with diabetes ages four years and above is the first and only nasally administered glucagon. It is compact, portable and ready to use in a single, fixed 3mg dose.
Primatene MIST
Primatene MIST, an over-the-counter epinephrine inhalation product, is indicated for the temporary relief of mild symptoms of intermittent asthma.
Glucagon for Injection Emergency Kit
Glucagon for injection is a difficult to manufacture injectable product. The company received the first-ever FDA approval of a generic version of rDNA Glucagon in the fourth quarter of 2020. Using a dedicated process and sophisticated characterization technology, the company demonstrated to the FDA that the company's highly purified synthetic peptide product is bioequivalent and therapeutically equivalent to the reference listed drug, or RLD, which is an rDNA product. Glucagon for injection emergency kit is indicated for the treatment of severe hypoglycemia and is used as a diagnostic aid.
Enoxaparin
Enoxaparin is a difficult to manufacture injectable form of low molecular weight heparin, which is used as an anticoagulant, and has multiple indications, including the prevention and treatment of deep vein thrombosis. Enoxaparin is difficult to produce in part because the API is not easily obtained or manufactured. The company manufactures the API for its enoxaparin product and perform all subsequent manufacturing of the finished product in-house.
REXTOVY (naloxone hydrochloride nasal spray) 4mg
REXTOVY is a prescription naloxone nasal spray product intended to be used for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. In March 2023, the FDA approved REXTOVY, which the company plans to launch in the first quarter of 2024.
Naloxone
The company sells two versions of naloxone injections indicated for the emergency treatment of known or suspected opioid overdose.
Other Marketed Products
Other finished pharmaceutical products that the company markets include the following:
Cortrosyn (cosyntropin for injection), a lyophilized powder that is indicated for use as a diagnostic agent in the screening of patients with adrenocortical insufficiency;
Amphadase, a bovine-sourced hyaluronidase injection that is used as an adjuvant in subcutaneous fluid administration for achieving hydration, to increase absorption and dispersion of other injected drugs, and in subcutaneous urography for improving absorption of radiopaque agents;
Epinephrine injection indicated for emergency treatment of allergic reactions, including anaphylaxis, and to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock;
Lidocaine jelly, a local anesthetic product used primarily for urological procedures;
Lidocaine topical solution, a local anesthetic used for a variety of procedures;
Phytonadione injection, an injection of Vitamin K1 that is used for newborn babies;
The company's portfolio of emergency syringe products, including critical care drugs, such as atropine, calcium chloride, dextrose, epinephrine, lidocaine, and sodium bicarbonate, are provided in pre-filled syringes and are designed for emergency use in hospital settings;
Morphine injection in prefilled syringe, pain management product indicated for use with Patient Controlled Analgesia (PCA) pumps;
Lorazepam injection, a sedative used prior to surgery and medical procedures;
Neostigmine methylsulfate injection, a cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants, such as gallamine and tubocurarine;
Isoproterenol hydrochloride injection, indicated for multiple uses, including mild or transient episodes of heart block that do not require electric shock or pacemaker therapy;
Ganirelix Acetate Injection, indicated for the inhibition of premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation; and
Vasopressin is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines.
Regadenoson is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress.
Product Candidates
The company seeks to develop product candidates with high technical barriers to competitive market entry that leverage the company's technical capabilities and other competitive advantages. The company focuses on generic and proprietary product candidates in the injectable, inhalable and intranasal markets. The company's pipeline products are in various stages of development, with a number of these candidates still in the early stages of development. The company's pipeline has over 20 product candidates, including generic ANDAs, biosimilar, and proprietary product candidates.
Generic Product Candidates
The company generally employs a strategy of developing generic product candidates that possess a combination of factors that present technical barriers to competition, including difficult formulations, which require complex characterizations, difficult manufacturing requirements and/or limited availability of raw materials. The company has generic ANDAs and biosimilar product candidates at various development stages that leverage the company's various technical capabilities, including:
injectable technologies, which include various delivery methods and sizes of pre-filled syringes, vials in solution, suspension and lyophilized forms;
inhalation technologies, which include MDIs and DPIs; and
sophisticated analytical technologies, including characterization and immunogenicity studies for complex molecules, particle engineering, sustained-release technology, peptide, protein and DNA analysis and synthesis.
Biosimial Product Candidates
The company's biosimilar pipeline, with a particular emphasis on interchangeable insulin analogs, targets a high-demand diabetes care sector. The recent filing of a Biologics License Application, or BLA, for insulin Aspart (AMP-004) was a pivotal step in the company's biosimilar program. The filing included using in-house developed technical platforms while navigating a complex regulatory environment while the company's intention to obtain interchangeable designations.
Further, the company is applying its technology platforms to develop additional product candidates in the company's biosimilar portfolio. The company is preparing for the regulatory submission of three additional interchangeable insulin product candidates, Insulin Aspart Mix (AMP-004m), Insulin Degludec (AMP-025), and Recombinant Human Insulin (AMP-005). Developed to meet stringent bioequivalence standards, these candidates will support the company's intention to meet the needs of its target markets.
A rigorous development strategy reinforces the company's commitment to developing biosimilar products and utilizes the company's vertically integrated structure when possible. Furthermore, the company's biosimilar product candidates are developed in accordance with regulatory guidelines for biosimilars, focusing on achieving interchangeability and bioequivalence to their respective reference products through rigorous pharmacokinetic and pharmacodynamics studies, supported by the company's expertise in areas such as protein engineering, creation of highly purified peptides/proteins, immunogenicity assessments, drug product characterization, and other internal technical platforms. This strategy is designed to deliver high-quality biosimilar products that meet all regulatory requirements for biosimilarity and interchangeability, thereby maximizing production efficiency.
Proprietary Product Candidates
The company's integrated technical skills and expertise provide a strong basis for the development of proprietary drug candidates. These skills include new chemical entity assessment, peptide and protein synthesis technology, complex formulation development, characterization analysis, and immunogenicity studies.
With respect to the company's proprietary pipeline strategy, the company has proprietary drug candidates at various development stages that leverage the company's various technical capabilities. The following paragraph summarizes the company's proprietary product candidates for which NDAs have been filed with the FDA.
Intranasal epinephrine
Intranasal epinephrine, a prescription epinephrine nasal spray product candidate, is intended to be used for emergency treatment of allergic reactions, including anaphylaxis to stinging insects, allergen immunotherapy, foods, drugs and other allergens.
Other Proprietary Product Candidates
In addition to intranasal epinephrine, the company has three other proprietary product candidates in development. These product candidates incorporate multiple indications utilizing a wide variety of the company's technical capabilities.
APIs
The company manufactures and sells two API products, Recombinant Human Insulin, or RHI API, and porcine insulin API, as a result of the company's acquisition of Merck Sharpe & Dohme's, or Merck's, API manufacturing business in Eragny-sur-Epte, France, or the Merck API Transaction, in April 2014. The acquisition aimed to enhance the company's vertical integration strategy as the company targets certain finished products for the injectable insulin market. However, the company continues to sell RHI API and porcine insulin API to third parties, which helps fund the company's vertical integration strategy.
Sales and Marketing
The company's products are marketed and sold to institutions such as hospitals, long-term care facilities, alternate care sites, clinics, and doctors' offices, and to retail pharmacies. Most institutional customers and retail pharmacies are members of one or more group purchasing organizations, which negotiate collective purchasing agreements on behalf of their members. These facilities purchase products through specialty distributors and wholesalers. The company has relationships with the major group purchasing organizations in the United States. The company also has relationships with major specialty distributors, wholesalers and retailers who distribute pharmaceutical products nationwide. Eli Lilly & Company, or Lilly, manufactures and sells BAQSIMI on the company's behalf pursuant to the terms of the Transition Services Agreement, or TSA.
The company's marketing department is responsible for establishing and maintaining contracts and relationships with the group purchasing organizations, distributors, retailers, wholesalers and the company's sales force is focused on promoting BAQSIMI with healthcare professionals. One or more of the company's proprietary product candidates may require deployment of a sales force either directly or through a strategic partner.
Competition
The company faces significant competition for its products and product candidates from pharmaceutical companies that focus on proprietary and generic injectable and inhalation markets, such as Pfizer, Inc., Sagent Pharmaceuticals, Inc., Akorn, Inc., Sandoz Inc., Viatris Inc., Fresenius Kabi USA, Nexus Pharmaceuticals, Apotex Corp, Amneal Biosciences, American Regent Inc., Hikma Pharmaceuticals USA, Inc., Par Pharmaceuticals, Cipla USA Inc., Meitheal Pharmaceuticals, Dr. Reddy's Laboratories, Inc., Sun Pharmaceuticals, Inc., Xeris, Pharmaceuticals, Novo Nordisk, Medefil Inc., Accord Healthcare, Eugia Pharma, Amring Pharmaceuticals, Bausch Health, Zydus Pharmaceuticals USA Inc., AuroMedics Pharma LLC, and Teva Pharmaceutical Industries Ltd.
Government Regulation
In the United States, the federal agencies that regulate the company's facilities, operations, employees, products (including their manufacture, sale, import and export) and services include: the U.S. Food and Drug Administration, the Drug Enforcement Agency, the Environmental Protection Agency, the Occupational Health & Safety Administration, the Department of Agriculture, the Department of Labor, the Department of Defense, Customs and Border Protection, the Department of Commerce, the Department of Treasury and others.
Many of the company's activities are subject to the jurisdiction of other federal regulatory and enforcement departments and agencies, such as the Department of Health and Human Services, or HHS, Office of the Inspector General, or OIG, the Federal Trade Commission (which also has the authority to regulate the advertising of consumer healthcare products, including over-the-counter drugs), the Department of Justice, the Drug Enforcement Administration, or DEA, the Veterans Administration, the Centers for Medicare and Medicaid Services and the Securities and Exchange Commission, or SEC.
The company and its suppliers are required to comply with applicable FDA manufacturing requirements contained in the FDA's cGMP regulations. The company and its suppliers are subject to periodic inspections of facilities by the FDA and other authorities to assess the company's compliance with applicable regulations.
The company is subject to the Open Payment Act. As a life sciences company, the company is subject to the federal anti-kickback statute, or AKS.
The company is subject to federal, state and local environmental laws and regulations, both the U.S. and foreign, including those promulgated by the Occupational Safety and Health Administration, the Environmental Protection Agency, the Department of Health and Human Services and the Air Quality Management District, which govern activities and operations that may have adverse environmental effects, such as discharges to air, soil and water, as well as handling and disposal practices for solid and hazardous wastes.
The company also must comply with data protection and data privacy requirements, such as the federal Health Insurance Portability and Accountability Act of 1996, the General Data Protection Regulation ((EU) 2016/679), the California Consumer Privacy Act, and the upcoming California Privacy Rights Act of 2020. Each of Amphastar and the company's U.S.-based subsidiaries subject to or covered by the federal Drug Supply Chain Security Act comply with the new requirements.
Research and Development
The company's research and development expense was $73.7 million for the year ended December 31, 2023.
History
Amphastar Pharmaceuticals, Inc., a California corporation, was founded in 1996. The company was incorporated in 2004.
