Qui Huat Hee is a senior scientist at Amgen’s biomanufacturing facility in Singapore. This state-of-the-art facility produces the same quantity of medicines as a conventional plant but is 75% smaller, giving it a significantly reduced environmental footprint.

LEADERSHIP

Amgen CEO Bob Bradway's 2023 Letter to Shareholders

Robert Bradway

Amgen performed well in 2023, serving millions of patients around the world with our innovative, life-changing medicines; advancing many promising new first-in-class molecules in our pipeline; completing a significant acquisition that establishes us as a leader in treating rare diseases; and delivering strong financial performance. Our achievements last year favorably position Amgen to generate attractive growth through the end of the decade and beyond.

Total revenues in 2023 increased 7% from the prior year to $28.2 billion, with non-GAAP earnings per share1 rising 5% to $18.65. Demand for our medicines from patients and physicians was strong in 2023, resulting in 15% volume growth, partially offset by a 3% decline in net selling price. Eighteen medicines2  generated record sales in 2023, and nine had sales exceeding $1 billion. Product sales outside the U.S. were approximately $7.6 billion in 2023, up 8%, with especially strong growth coming from the Asia-Pacific region. We invested $4.8 billion in research and development in 2023, an increase of 8% from the prior year, to advance the broadest and deepest pipeline in our history.

Amgen delivered total shareholder return of 13% in 2023 and 232% over the past ten years, ahead of our peer set in both time frames. We increased our dividend per share by 10% in 2023 over 2022, the twelfth consecutive year of dividend increases.

$28.2B
2023 Total Revenues
$18.65
Non-GAAP
Earnings Per Share1
$4.8B
GAAP Research and Development Investment
49.8%
Non-GAAP
Operating Margin1,4

Our performance last year included $954 million in sales3 associated with our acquisition of Horizon Therapeutics plc (Horizon), a leading provider of medicines to treat rare inflammatory diseases, which Amgen completed on October 6, 2023, for approximately $27.8 billion. I will say more below about the medicines we acquired in this transaction. Broadly, the acquisition reflects our ongoing commitment to pursuing the best innovation, inside our own labs and beyond. Over time, roughly half our sales have come from medicines discovered and developed internally, with the other half coming from therapies that we have sourced externally. 

Four Therapeutic Pillars of Growth

Today, our portfolio is balanced across four therapeutic pillars of growth: General Medicine, Oncology, Inflammation, and now Rare Disease. In each pillar, we have numerous well-established medicines currently on the market around the world; new innovative treatments advancing through our pipeline; and biosimilars, either marketed or planned, that deliver savings to healthcare systems. Our success is not overly reliant on any one product or therapeutic area, and our presence in roughly 100 countries around the world gives us geographic balance as well.

Furthermore, at a time of intense pressure on drug pricing worldwide — which we don't expect to go away — we've built a portfolio that is designed to deliver growth through volume increases.

General Medicine

In our General Medicine business, sales of our cholesterol treatment Repatha® rose 26% from the prior year to $1.6 billion, with sales of our osteoporosis medicines EVENITY® and Prolia® increasing 47% to $1.2 billion and 12% to $4.0 billion, respectively.

In our pipeline for General Medicine, we are rapidly advancing potentially differentiated, early-stage treatments for obesity, the furthest along of which, maridebart cafraglutide, is currently being studied in a Phase 2 clinical trial. In a Phase 1 trial, maridebart cafraglutide demonstrated rapid, substantial, and sustained weight loss when administered monthly. It is estimated that more than 650 million people worldwide live with obesity, a complex disease with multiple underlying causes. Given the complexity of the disease, we believe that a variety of medicines will ultimately be needed to treat this patient population effectively.

Olpasiran is another promising new medicine in our General Medicine pipeline. Phase 2 data released in 2022 showed reductions in lipoprotein(a) — a type of "bad" cholesterol that is genetically determined and cannot be modified by diet or exercise — of as much as 95% in patients with established cardiovascular disease. We have rapidly enrolled thousands of patients around the world in a Phase 3 cardiovascular-outcomes trial for olpasiran, underscoring the medical community's strong interest in this medicine.

Oncology

Our Oncology business delivered sales of $9.2 billion in 2023. Sales of BLINCYTO®, a treatment for acute lymphoblastic leukemia, rose 48% in 2023 to $861 million. Sales of KYPROLIS® for multiple myeloma and Vectibix® for colorectal cancer grew 13% to $1.4 billion and 10% to $984 million, respectively, in 2023.

In our Oncology pipeline, Amgen was granted three Breakthrough Therapy Designations by the U.S. Food and Drug Administration (FDA) last year: for tarlatamab in small cell lung cancer; for BLINCYTO in early-stage acute lymphoblastic leukemia, and for LUMAKRAS®/LUMYKRAS™ in combination with Vectibix in colorectal cancer. The FDA is scheduled to complete its reviews of tarlatamab and BLINCYTO this year. New treatment options are very much needed for all three of these diseases. For example, there have been no new treatments for small cell lung cancer for decades, and the disease today has a five-year survival rate of just 3%.

Elsewhere in our Oncology pipeline, we are studying bemarituzumab for gastric cancer, which is the fifth-leading cause of cancer death worldwide and particularly prevalent in the Asia-Pacific region; and xaluritamig for prostate cancer, which is the second-leading cause of cancer death in American men.

Today Amgen offers high-quality biosimilars to some of the most-prescribed cancer treatments in the world, including MVASI® (a biosimilar to Avastin®5), KANJINTI® (a biosimilar to Herceptin®5), and RIABNI® (a biosimilar to RITUXAN®5). These three medicines together generated $1.1 billion in 2023 sales. Our Oncology pipeline includes a biosimilar to OPDIVO®,5 one of the largest-selling cancer medicines in history.

Inflammation

Amgen has been a leader in treating inflammatory diseases for decades. Sales in 2023 of TEZSPIRE®, a treatment for severe asthma, increased more than threefold in its second year on the market to $567 million. We are also studying TEZSPIRE in Phase 3 trials for chronic rhinosinusitis with nasal polyps and for eosinophilic esophagitis, and in a Phase 2 trial for chronic obstructive pulmonary disease, which is the world's third-leading cause of death. 

Sales of our psoriasis treatment Otezla® declined 4% to $2.2 billion as we faced increased competition in the U.S. We expect future growth of Otezla to be driven by its well-established safety and efficacy profile, approved use in mild-to-moderate psoriasis, and ease of administration.

In our Inflammation pipeline, we anticipate Phase 3 data later this year from the first of eight trials studying rocatinlimab in moderate-to-severe atopic dermatitis in collaboration with our long-time partner, Kyowa Kirin Co., Ltd.

Sales of AMJEVITA®/AMGEVITA™, Amgen's biosimilar to HUMIRA®5 that is now available in markets around the world, rose 36% in 2023 to $626 million. In the U.S., we also offer AVSOLA®, a biosimilar to REMICADE®,5 and, in 2023, we received U.S. FDA approval for Wezlana™, a biosimilar to STELARA®.5

Rare Disease

In our new Rare Disease business, medicines acquired in the Horizon deal discussed above include TEPEZZA® for thyroid eye disease, a progressive and potentially vision-threatening disease that can cause symptoms such as eye bulging and double vision; KRYSTEXXA® for uncontrolled gout, which can lead to visible lumps under the skin, joint pain or stiffness, and damage to joints and bones; and UPLIZNA® for neuromyelitis optica spectrum disorder, an inflammatory disease that most often affects the optic nerves and spinal cord. 

TEPEZZA, KRYSTEXXA, and UPLIZNA are all very early in their life cycles and — by leveraging Amgen's extensive global presence, world-class biologics capabilities, and extensive experience in inflammation — we believe they have the potential to reach more patients around the world. Toward that end, we are pursuing launches in new geographic markets, new indications, and/or new formulations to expand the impact of each of these medicines. 

TAVNEOS®, acquired in 2022, treats anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, an autoimmune disease that leads to the inflammation and eventual destruction of small blood vessels in vital organs such as the kidneys. Since we completed the acquisition, the number of patients who have been prescribed TAVNEOS has more than doubled, and we see opportunity for continued growth.

In our Rare Disease pipeline, we are currently enrolling patients in a Phase 3 clinical trial for dazodalibep in Sjögren's disease, an autoimmune disorder in which the immune system attacks the glands that make moisture in the eyes, mouth, and other parts of the body. We are also enrolling Phase 2 trials for fipaxalparant in idiopathic pulmonary fibrosis, a condition in which the lungs become scarred and breathing becomes increasingly difficult, and in diffuse cutaneous systemic sclerosis, which can cause skin hardening and problems in many organs of the body.

We also have two biosimilars in the Rare Disease space. Approved in Europe and under regulatory review in the U.S., BKEMV™/BEKEMV™ is a biosimilar to SOLIRIS®,5 which treats generalized myasthenia gravis, a disease that impacts the neuromuscular system. Our biosimilar to EYLEA®5 is under regulatory review in the U.S. as a treatment for wet age-related macular degeneration.

You can find more information about our approved medicines at www.amgen.com/products.

To learn more about our pipeline, please visit www.amgenpipeline.com.

Accelerating Innovation

At a time when a rapidly aging global population needs more innovation, the convergence of "biotech" and "tech" is enabling Amgen to innovate with greater speed, confidence, and efficiency — an incredibly exciting moment for which we have been preparing for over a decade.

In 2012, for example, we had accumulated detailed genetic and health information from approximately 100,000 people, all from Iceland, which has one of the world's most homogenous populations. Today, we have such information from more than 3 million volunteers from around the world — and new technologies are enabling us to quickly derive powerful insights from this massive amount of data, which help guide our research and development work. 

To give another example, in the past, we have built biologic medicines using proteins that naturally occur in the human body, a process involving multiyear cycles in which we engineered and tested numerous prototypes before moving a single molecule into clinical trials. Nevertheless, these protein-based medicines often behaved unpredictably, failing to achieve the desired outcome or yielding unacceptable side effects. Today, using artificial intelligence and machine learning, we can design proteins from scratch that are more suitable to be made into drugs than those found in nature — potentially enabling us to move faster and with a higher likelihood of success.

To ensure that we are fully capitalizing on new technologies — not just in R&D, but across the entire company — we tapped Dr. David Reese in late 2023 to become Amgen's first-ever chief technology officer. Dr. Reese, a physician-scientist, has been with Amgen for nearly 20 years and has led our R&D organization since 2018, spearheading the development of the robust pipeline we possess today.

Dr. James "Jay" Bradner is our new head of R&D and chief scientific officer. Dr. Bradner is also a physician-scientist and a seasoned R&D leader, having previously served as president of the Novartis Institutes for BioMedical Research. He also has served as a faculty member at Harvard Medical School and, immediately prior to joining Amgen, was a practicing oncologist at the Dana-Farber Cancer Institute.

I'm excited by the work that Dave, Jay, and the rest of our team will do together to use technology to accelerate innovation at Amgen for the good of patients and the long-term growth of our business.

Supporting Our People

Technology is only as good as the people who use it — and I believe that Amgen's people are the best in the business. We regularly survey our employees and they consistently tell us that they are passionate about our Mission to serve patients, know the Company's priorities, and understand the role they play as individuals in helping Amgen as a whole succeed.

While we are pleased to be named to numerous "best" lists — including Forbes magazine's list of "America's Best Large Employers" and Glassdoor's ranking of the "100 Best Large Places to Work in the United States" — we take nothing for granted and are always looking for ways to improve.

Last year, for example, in response to feedback from employees looking for greater career development opportunities, we launched the Talent Marketplace, where employees can be matched with opportunities at Amgen that best fit their skills and interests. Today, more than 9,000 employees worldwide are active participants in the Talent Marketplace.

Inspiring the Next Generation of Innovators

Having the best employees today is critical, but we also want to nurture and inspire the next generation of innovators — especially in the wake of learning losses due to the COVID-19 pandemic and growing societal skepticism about science.

Guided by the belief that everyone needs science and science needs everyone, the Amgen Foundation has invested nearly $270 million over more than 30 years to provide best-in-class, no-cost science education programs that now reach approximately 25 million students annually around the world.   

In 2023, the Amgen Foundation announced a new investment of more than $12 million to expand the Amgen Biotech Experience (ABE), a free science education program that has provided nearly a million high school students globally with hands-on biotech experiences. The new funding will be used to bring ABE to communities in Brazil, Mexico, and South Africa, with the goal of reaching an additional 180,000 students over the next two years.

Last year, the Amgen Foundation also committed over $8 million in new funding to the Amgen Scholars Program, an undergraduate summer research experience hosted at premier educational institutions around the world. More than 5,300 students have completed the program to date, and this new investment will enable an additional 500 students to participate over the next two years.

You can learn more about our commitment to good corporate citizenship at www.amgen.com/responsibility.

A Future of Opportunity

This is an exciting time to be at Amgen. Thanks to the hard work, commitment, and ingenuity of our approximately 27,000 employees globally, we are well positioned to serve millions more patients suffering from some of the world's most serious diseases — and, by so doing, to create significant value over the long term for you, our shareholders.

On behalf of Amgen's board of directors, our senior leadership team, and our employees around the world, I thank you for your ongoing support of our Company and the important work we do.

Robert A. Bradway
Chairman and Chief Executive Officer
March 21, 2024



Stories From 2023


Raul Lazaro

Overcoming Stereotypes

Raul Lazaro (pictured) is a researcher at Amgen whose love for science helped him to overcome the stereotypes that some might attach to a son of migrant workers from Mexico. He now shares his story with young people as a volunteer with the Amgen Biotech Experience (ABE), a program that uses hands-on experiments to inspire the next generation of innovators.

"In some communities, you're told that your options are limited," Lazaro says. "You have a picture of a scientist in your head, and they don't look like you. With ABE, I get to show students how working in science can change your life."

Linda Ohlrich, a teacher at Rio Mesa High School in Southern California, says, "I have students in my Biology class from a diverse set of backgrounds, with several from families living below the poverty line. Raul was able to show my students that you can work in science regardless of where you come from. Put a micropipette in your hand, and you never know where it will lead you."

Thomas

Restarting the Music

Thomas (pictured) heard the calling to become a musician in 1964 when, as a middle schooler, he saw the Beatles perform on The Ed Sullivan Show. More than 40 years later, uncontrolled gout stole his ability to play guitar when his fingers swelled severely from the buildup of uric acid crystals.

"My fingers would lock in place over a chord ... you obviously cannot play guitar that way," he says. "I became depressed. I was in a really dark place."

Thomas' passion for music returned in full force after he began treatment with KRYSTEXXA, a medicine designed to break up crystalized uric acid deposits. The medicine is now part of Amgen's Rare Disease business following the 2023 acquisition of Horizon.

"I remember the day I got my first treatment: September 28, 2022," he says.

Changes in his hands and fingers weren't far behind. The swelling went down. The pain subsided. Dexterity returned. The improvement was steady, he says, as he continued to receive an infusion every two weeks.

"Because KRYSTEXXA makes it possible to play again, I can take hold of life once more," he says. "There aren't adequate words to articulate what being able to play guitar again after so long has added to my life."

Hearing From Patients Around the World

In 2023, Amgen celebrated Mission Week, giving employees around the world the chance to hear directly from some of the patients we serve. Lorenda, who lives with ANCA-associated vasculitis, flew for the first time in 25 years, traveling from her home in Alabama to Amgen's headquarters in Southern California.

"Because of the work you do here," she said, "my granddaughters get to know me personally instead of someone showing them photos and videos and speaking about me in the past tense."

Bahija, a patient advocate and leukemia survivor, spoke to a gathering of Amgen employees in Munich. "Your passion, your dedication, and your tireless efforts — it matters," she said.

More than 10,000 employees around the world either attended live or tuned in virtually to a patient panel, with nearly 95% saying afterward that the events of the week gave them motivation to better serve patients and an improved understanding of the pressing issues patients face.


Employees celebrated Mission Week

Employees celebrated Mission Week at Amgen's world headquarters in Thousand Oaks, CA.

Mission Week at Amgen's headquarters in Singapore

Employees celebrated Mission Week at Amgen's headquarters in Singapore.

Living with acute lymphoblastic leukemia

Ryan (left) is living with acute lymphoblastic leukemia, while Lorenda (right) lives with ANCA-associated vasculitis.

Living with cardiovascular disease

Magdalene is living with cardiovascular disease.

Living with myeloma

Jürgen (shown above with his wife, Diane) lives with myeloma.

A leukemia survivor

Bahija is a leukemia survivor.

Gillian Winstanley

Fostering Career Development

Like many Amgen employees, Gillian Winstanley (pictured) is innately curious and always looking for opportunities to do new things and build new skills. So when Amgen launched a new Talent Marketplace to match interested employees with short-term, project-based opportunities, Winstanley was one of the first to give it a try.

"I wanted to learn more aspects of the business and how to think strategically and test my decision-making skills," says Winstanley, who works in Global Safety for Amgen in Canada and has now taken on three projects via the Talent Marketplace. "I received a much broader view of the organization, expanded my network, and learned about functions that I didn't even know existed."

Amgen launched the Talent Marketplace using employee feedback to help people at all levels of the organization build and strengthen their skills to meet the changing needs of the business, and connect with global opportunities across the company.

Thomas

Celebrating Diverse Scientists

In 2023, a new mural was installed at Amgen headquarters, highlighting a diverse range of scientists who have made significant contributions to drug discovery and development.

"I imagined what it might mean to create a new scientist wall here at Amgen, one that more fully reflects our community," said principal scientist Sarah Van Driesche (above), who initiated the mural effort.

When the idea was presented to Dr. David Reese, Amgen's chief technology officer, his reaction was simple: "We have to do this."

Among those featured on the mural are Fu-Kuen Lin, whose breakthrough research paved the way for Amgen's first medicine, and David Baltimore, a long-time Amgen board member and Nobel Prize winner.


  1. Non-GAAP financial measure. See reconciliations to U.S. generally accepted accounting principles (GAAP) accompanying this letter.
  2. Includes product sales for the full year 2023 from UPLIZNA®, KRYSTEXXA®, and RAVICTI® in connection with the Horizon acquisition.
  3. Product sales between October 6, 2023, and December 31, 2023.
  4. Non-GAAP operating margin is calculated as a percentage of product sales.
  5. Avastin is a registered trademark of Genentech, Inc.
    Herceptin is a registered trademark of Genentech, Inc.
    RITUXAN is a registered trademark of Biogen MA Inc.
    OPDIVO is a registered trademark of Bristol-Myers Squibb Company.
    HUMIRA is a registered trademark of AbbVie Biotechnology Ltd.
    REMICADE is a registered trademark of Janssen Biotech, Inc.
    STELARA is a registered trademark of Johnson & Johnson.
    SOLIRIS is a registered trademark of Alexion Pharmaceuticals, Inc.
    EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc.


Amgen Inc. GAAP to Non-GAAP Reconciliations (Dollars in millions) (Unaudited)
Twelve months ended December 31, 2023 2022
GAAP operating income $7,897 $9,566
Adjustments to operating income:
Acquisition-related expenses (a) 5,234 2,619
Certain charges pursuant to our restructuring and cost savings initiatives (b) 263 (8)
Certain other expenses (c) 5 584
Total adjustments to operating income 5,502 3,195
Non-GAAP operating income $13,399 $12,761
GAAP operating income as a percentage of product sales 29.3% 38.6%
Adjustments to operating income 20.5 12.9
Non-GAAP operating income as a percentage of product sales 49.8% 51.5%
GAAP net income $6,717 $6,552
Adjustments to net income:
Adjustments to operating income 5,502 3,195
Adjustments to interest expense, net(d) 807 5
Adjustments to other income (expense), net(e) (2,147) 554
Income tax effect of the above adjustments(f) (846) (690)
Other income tax adjustments(g) 1 (46)
Total adjustments to net income 3,317 3,018
Non-GAAP net income $10,034 $9,570

 

The following table presents the computations for GAAP and non-GAAP diluted earnings per share (EPS):

Amgen Inc. GAAP to Non-GAAP Reconciliations (In millions, except per share data) (Unaudited)
Twelve months ended December 31, 2023 2022
  GAAP Non-GAAP GAAP Non-GAAP
Net income $6,717 $10,034 $6,552 $9,570
Weighted-average shares for diluted EPS 538 538 541 541
Diluted EPS $12.49 $18.65 $12.11 $17.69

(a) The adjustments related primarily to noncash amortization of intangible assets from business acquisitions. For the year ended December 31, 2023, the adjustments also included a net impairment charge for AMG 340.

(b) The adjustments related to headcount charges, such as severance, and to asset charges, such as asset impairments and other related costs resulting from rationalization of our geographic footprint.

(c) For the year ended December 31, 2022, the adjustments related primarily to a loss on the divestiture of Gensenta İlaç Sanayi ve Ticaret A.Ş.

(d) For the year ended December 31, 2023, the adjustments included (i) interest expense on senior notes issued in March 2023 and (ii) debt issuance costs and other fees related to our bridge credit and term loan credit agreements, incurred prior to the closing of our acquisition of Horizon.

(e) For the year ended December 31, 2023, the adjustments related primarily to our BeiGene, Ltd. (BeiGene) equity fair value adjustment and interest income on senior notes issued in March 2023 recognized prior to the closing of our acquisition of Horizon. In the first quarter of 2023, we began to account for our ownership interest in BeiGene as an equity security with a readily determinable fair value, with changes in fair value recorded in Other income (expense), net. For the year ended December 31, 2022, the adjustments related to equity investment losses and the amortization of the basis difference from our BeiGene equity method investment.

(f) The tax effect of the adjustments between our GAAP and non-GAAP results takes into account the tax treatment and related tax rate(s) that apply to each adjustment in the applicable tax jurisdiction(s). Generally, this results in a tax impact at the U.S. marginal tax rate for certain adjustments, including the majority of amortization of intangible assets and certain gains and losses on our investments in equity securities, whereas the tax impact of other adjustments, including expenses related to restructuring and cost savings initiatives, depends on whether the amounts are deductible in the respective tax jurisdictions and the applicable tax rate(s) in those jurisdictions.

(g) The adjustments related to certain acquisition items, prior period and other items excluded from GAAP earnings.


Forward-Looking Statements:

This communication contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon (including the prospective performance and outlook of Horizon's business, performance and opportunities and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this communication and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. We or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

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