amgn-20211231

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Form 10-K

(Mark One)

For the fiscal year ended December 31, 2021

Commission file number 001-37702

Amgen Inc.

(Exact name of registrant as specified in its charter)

Thousand Oaks

California

(Address of principal executive offices) (Zip Code)

(805) 447-1000

(Registrant’s telephone number, including area code)

Securities registered pursuant to Section 12(b) of the Act:

Title of each class Trading Symbol (s) Name of each exchange on which registered

Common stock, $0.0001 par value AMGN The Nasdaq Stock Market LLC

2.00% Senior Notes due 2026 AMGN26 The Nasdaq Stock Market LLC

Securities registered pursuant to Section 12(g) of the Act: None

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yesý No ̈

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act.Yes ̈Noý

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or Section 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.Yesý No ̈

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).Yesý No ̈

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

☒ ☐ ☐ ☐ ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ̈

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☒

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act)Yes ☐ No ý

The approximate aggregate market value of voting and non-voting stock held by non-affiliates of the registrant was $137,531,019,585 as of June 30, 2021.(A)

(A)Excludes 811,415 shares of common stock held by directors and executive officers, and any stockholders whose ownership exceeds ten percent of the shares outstanding, at June 30, 2021. Exclusion of shares held by any person should not be construed to indicate that such person possesses the power, directly or indirectly, to direct or cause the direction of the management or policies of the registrant, or that such person is controlled by or under common control with the registrant.

557,029,370

(Number of shares of common stock outstanding as of February 11, 2022)

DOCUMENTS INCORPORATED BY REFERENCE

Specified portions of the registrant’s Proxy Statement with respect to the 2022 Annual Meeting of Stockholders to be held May 17, 2022, are incorporated by reference into Part III of this annual report.

INDEX

Page No.

Defined Terms and Products ii

PART I 1

Item 1. BUSINESS 1

Significant Developments 1

Marketing, Distribution and Selected Marketed Products 3

Reimbursement 9

Manufacturing, Distribution and Raw Materials 11

Government Regulation 12

Research and Development and Selected Product Candidates 16

Business Relationships 21

Human Capital Resources 22

Information about our Executive Officers 24

Geographic Area Financial Information 25

Investor Information 26

Item 1A. RISK FACTORS 26

Item 1B. UNRESOLVED STAFF COMMENTS 50

Item 2. PROPERTIES 51

Item 3. LEGAL PROCEEDINGS 51

Item 4. MINE SAFETY DISCLOSURES 51

Item 6. RESERVED 53

Item 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 73

Item 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 75

Item 9A. CONTROLS AND PROCEDURES 76

Item 9B. OTHER INFORMATION 78

PART III 78

Item 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 78

Item 11. EXECUTIVE COMPENSATION 78

Item 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 80

Item 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 81

SIGNATURES 88

Defined Terms and Products

Defined terms

We use several terms in this Form 10-K—including but not limited to those that are finance, regulation and disease-state related—as well as names of other companies, which are given below.

Term Description

2017 Tax Act Tax Cuts and Jobs Act of 2017

AbbVie AbbVie Inc.

ACA Affordable Care Act

aHUS atypical hemolytic uremic syndrome

ALL acute lymphoblastic leukemia

AMD age-related macular degeneration

Amended 2009 Plan Amended and Restated 2009 Equity Incentive Plan

ANDA Abbreviated New Drug Application

AOCI accumulated other comprehensive income (loss)

AstraZeneca AstraZeneca plc

BAFF B-cell activating factor

BeiGene BeiGene, Ltd.

BiTE® bispecific T-cell engager

BLA Biologics License Application

BMS Bristol Myers Squibb Company

BPCIA Biologics Price Competition and Innovation Act of 2009

Celgene Celgene Corporation

CGRP calcitonin gene-related peptide

chemotherapy anticancer medicines

CHMP Committee for Medicinal Products for Human Use

CIT chemotherapy-induced thrombocytopenia

CKD chronic kidney disease

CMS Centers for Medicare & Medicaid Services

COSO Committee of Sponsoring Organizations of the Treadway Commission

COVID-19 coronavirus disease 2019

CV cardiovascular

DaVita DaVita Inc.

DLL3 delta-like ligand 3

DOJ U.S. Department of Justice

DoR duration of response

EC European Commission

EMA European Medicines Agency

EPS earnings per share

ERG employee resource group

ESA erythropoiesis-stimulating agent

ESG environmental, social and governance

ESRD end-stage renal disease

EU European Union

FASB Financial Accounting Standards Board

FCPA U.S. Foreign Corrupt Practices Act

FDA U.S. Food and Drug Administration

FDCA Federal Food, Drug, and Cosmetic Act

FGFR2b fibroblast growth factor receptor 2b

Fitch Fitch Ratings, Inc.

Term Description

Five Prime Five Prime Therapeutics, Inc.

FOMBPR Financial Oversight and Management Board for Puerto Rico

FTC Federal Trade Commission

GAAP U.S. generally accepted accounting principles

GDPR General Data Protection Regulation

GEJ gastroesophageal junction

HeFH heterozygous familial hypercholesterolemia

HER2 human epidermal growth factor receptor 2

HGRAC Human Genetic Resources Administration of China

HHS U.S. Department of Health & Human Services

HLE half-life extended

HoFH homozygous familial hypercholesterolemia

ICOSL inducible costimulatory ligand

IL interleukin

IND Investigational New Drug Application

IPR&D in-process research and development

IRP international reference pricing

IRS Internal Revenue Service

ITP immune thrombocytopenia

J&J Johnson & Johnson

Janssen Janssen Biotech, Inc.

K-A Kirin-Amgen, Inc.

Kirin Kirin Holdings Company, Limited

KKC Kyowa Kirin Co., Ltd.

LDL-C low-density lipoprotein cholesterol

LIBOR London Interbank Offered Rate

Lilly Eli Lilly and Company

mCRPC metastatic castrate-resistant prostate cancer

MD&A management’s discussion and analysis

MFN most favored nation

Moody’s Moody’s Investors Service, Inc.

MRD minimal residual disease

Neumora Neumora Therapeutics, Inc.

NOL net operating loss

Novartis Novartis Pharma AG

NSCLC non-small cell lung cancer

Nuevolution Nuevolution AB

OECD Organization for Economic Co-operation and Development

OIG Office of Inspector General

ORR objective response rate

PBM pharmacy benefit manager

PCSK9 proprotein convertase subtilisin/kexin type 9

PDE4 phosphodiesterase 4

PDUFA Prescription Drug User Fee Act

PFS progression-free survival

PNH paroxysmal nocturnal hemoglobinuria

Profit Sharing Plan Amgen Profit Sharing Plan for Employees in Ireland

PROMESA Puerto Rico Oversight, Management, and Economic Stability Act

iii

Term Description

PTAB Patent Trial and Appeal Board

R&D research and development

RANKL receptor activator of nuclear factor kappa-B ligand

RAR Revenue Agent Report

REMS risk evaluation and mitigation strategy

ROU right-of-use

ROW rest of world

RSUs restricted stock units

S&P Standard & Poor’s Financial Services LLC

SEC U.S. Securities and Exchange Commission

SG&A selling, general and administrative

siRNA small interfering RNA

sNDA supplemental New Drug Application

SoC standard of care

SOFR Secured Overnight Financing Rate

SRE skeletal-related event

Takeda Takeda Pharmaceutical Company Limited

TDAPA transitional drug add-on payment adjustment

Teneobio Teneobio, Inc.

TNF tumor necrosis factor

TPO-RA thrombopoietin receptor agonist

U.S. Treasury U.S. Department of Treasury

UCLA University of California, Los Angeles

USPTO U.S. Patent and Trademark Office

UTB unrecognized tax benefit

VEGFR vascular endothelial growth factor receptor

Products

The brand names of our products, our delivery devices and certain of our product candidates and their associated generic names are given below.

Term Description

Acapatamab Acapatamab (formerly AMG 160)

Aimovig Aimovig® (erenumab-aooe)

AMGEVITA AMGEVITATM (adalimumab)

AMJEVITA AMJEVITATM (adalimumab-atto)

Aranesp Aranesp® (darbepoetin alfa)

AutoTouch AutoTouch®

AVSOLA AVSOLA® (infliximab-axxq)

BLINCYTO BLINCYTO® (blinatumomab)

Efavaleukin alfa Efavaleukin alfa (formerly AMG 592)

ENBREL Enbrel® (etanercept)

ENBREL Mini ENBREL Mini®

EPOGEN EPOGEN® (epoetin alfa)

EVENITY EVENITY® (romosozumab-aqqg)

IMLYGIC IMLYGIC® (talimogene laherparepvec)

KANJINTI KANJINTI® (trastuzumab-anns)

KYPROLIS KYPROLIS® (carfilzomib)

LUMAKRAS/LUMYKRAS LUMAKRAS® / LUMYKRASTM (sotorasib)

MVASI MVASI® (bevacizumab-awwb)

Neulasta Neulasta® (pegfilgrastim)

NEUPOGEN NEUPOGEN® (filgrastim)

Nplate Nplate® (romiplostim)

Olpasiran Olpasiran (formerly AMG 890)

Onpro Onpro®

Ordesekimab Ordesekimab (formerly AMG 714)

Otezla Otezla® (apremilast)

Parsabiv Parsabiv® (etelcalcetide)

Pavurutamab Pavurutamab (formerly AMG 701)

Prolia Prolia® (denosumab)

Repatha Repatha® (evolocumab)

RIABNI RIABNITM (rituximab-arrx)

Rozibafusp alfa Rozibafusp alfa (formerly AMG 570)

Sensipar/Mimpara Sensipar®/MimparaTM (cinacalcet)

SureClick SureClick®

Tarlatamab Tarlatamab (formerly AMG 757)

TEZSPIRE TEZSPIRETM (tezepelumab-ekko)

Vectibix Vectibix® (panitumumab)

XGEVA XGEVA® (denosumab)

Products referenced in this report that are not included in the above list are trademarks of their respective owners. They are Avastin®, Cosentyx®, DARZALEX®, DARZALEX FASPRO®, EYLEA®, Fulphila®, Herceptin®, HUMIRA®, POMALYST®/IMNOVID®, PRALUENT®, PROCRIT®, PROMACTA®/REVOLADETM, Remicade®, REVLIMID®, RINVOQ®, Rituxan®/MabThera®, Skyrizi®, SOLIRIS®, STELARA®, Taltz®, Tremfya®, UDENYCA®, VELCADE® and Xeljanz®.

PART I

Item 1. BUSINESS

Amgen Inc. (including its subsidiaries, referred to as “Amgen,” “the Company,” “we,” “our” or “us”) is a biotechnology company committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

Amgen was incorporated in California in 1980 and became a Delaware corporation in 1987. We have a presence in approximately 100 countries worldwide. Amgen operates in one business segment: human therapeutics.

Significant Developments

Following is a summary of significant developments affecting our business that have occurred and that we have reported since the filing of our Annual Report on Form 10-K for the year ended December 31, 2020.

Business Development

Five Prime Therapeutics acquisition

•On April 16, 2021, Amgen completed its acquisition of Five Prime, a public clinical-stage biotechnology company focused on developing immuno-oncology and targeted cancer therapies, for approximately $1.6 billion in cash, net of cash acquired.

•In April 2021, the FDA granted Breakthrough Therapy designation for bemarituzumab as first-line treatment for patients with FGFR2b overexpressing and HER2-negative metastatic and locally advanced gastric and gastroesophageal adenocarcinoma in combination with fluoropyrimidine, leucovorin and oxaliplatin based on an FDA-approved companion diagnostic assay showing at least 10% of tumor cells overexpressing FGFR2b.

KKC collaboration

•We and KKC entered into an agreement, effective July 30, 2021, to jointly develop and commercialize KKC’s potential first-in-class, phase 3-ready anti-OX40 fully human monoclonal antibody in development for the treatment of atopic dermatitis, with potential in other autoimmune diseases.

Teneobio acquisition

•On October 19, 2021, Amgen completed its acquisition of Teneobio, a privately held, clinical-stage biotechnology company developing a new class of biologics called human heavy-chain antibodies, which are single-chain antibodies composed of the human heavy-chain domain, for $900 million as well as future contingent milestone payments potentially worth up to an additional $1.6 billion upon the achievement of certain developmental and regulatory events.

Products/Pipeline

Inflammation

Otezla

•In December 2021, we announced that the FDA had approved the expanded indication for Otezla for the treatment of adult patients with plaque psoriasis, who are candidates for phototherapy or systemic therapy, across all severities.

TEZSPIRE

•In December 2021, we and AstraZeneca announced that the FDA had approved TEZSPIRE for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.

Oncology/Hematology

LUMAKRAS/LUMYKRAS

•In May 2021, we announced that the FDA had approved LUMAKRAS for the treatment of adult patients with KRAS G12C–mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. LUMAKRAS received accelerated approval based on ORR and DoR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial or trials.

•In January 2022, we announced that the EC had granted conditional marketing authorization for LUMYKRAS for the treatment of adults with advanced NSCLC with KRAS G12C mutation and who have progressed after at least one prior line of systemic therapy. We also announced that LUMAKRAS had been approved in Japan for the treatment of KRAS G12C-mutated positive, unresectable, advanced and/or recurrent NSCLC that has progressed after systemic anticancer therapy.

KYPROLIS

•In December 2021, we announced that the FDA had approved the expansion of the KYPROLIS prescribing information to include its use in combination with DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.

Operations

New manufacturing facilities

We announced plans to expand our United States–based manufacturing footprint.

•In August 2021, we announced plans to build a drug substance plant in North Carolina that will increase our manufacturing network capacity to reliably supply more medicines for patients.

•In November 2021, we broke ground to build an advanced assembly and packaging plant in Ohio. The new facility will assemble and package vials and syringes to support the growing demand for our medicines.

We expect that both of these facilities will be built faster and at lower cost than traditional plants. Once completed, both will also utilize cutting-edge technologies to be more efficient and environmentally friendly than traditional plants.

COVID-19 pandemic

A novel strain of coronavirus (SARS-CoV-2, or severe acute respiratory syndrome coronavirus 2, causing COVID-19) was declared a global pandemic by the World Health Organization on March 11, 2020. Since the onset of the pandemic in 2020, we have been closely monitoring the pandemic’s effects on our global operations. To date, we have not experienced disruptions to or shortages of our supply of medicines. We continue to take appropriate steps to minimize risks to our employees. Employee access to company facilities has been in accordance with applicable government health and safety protocols and guidance issued in response to the COVID-19 pandemic. The pandemic has shifted how we work as an organization and in the fourth quarter of 2021, we enabled our U.S. based workforce to return to the workplace for work that benefits from face-to-face interaction, while maintaining appropriate safety measures to ensure staff well-being. For further discussion, see Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations—Overview, Selected Financial Information and Results of Operations. For a discussion of the risks presented by the COVID-19 pandemic to our results, see Risk Factors in Item 1A.

Marketing, Distribution and Selected Marketed Products

The largest concentration of our sales and marketing forces is based in the United States and Europe. In recent years, we have expanded the commercialization and marketing of our products into other geographic territories, including China and Japan and other parts of Asia, the Middle East and Latin America. This expansion has occurred, and is expected to continue to occur, by establishing our own affiliates, by acquiring existing third-party businesses or product rights or by collaborating with third parties. See Business Relationships for our significant alliances. Whether we use our own sales and marketing forces or a third party’s services varies across these markets. Such use typically depends on several factors, including the nature of entry into the new market, the size of an opportunity and operational capabilities. Together with our collaborators, we market our products to healthcare providers, including physicians or their clinics, dialysis centers, hospitals and pharmacies.

In the United States, substantially all of our sales are to pharmaceutical wholesale distributors, which are the principal means of distributing our products to healthcare providers. We also market certain products through direct-to-consumer channels, including print, television and online media. For further discussion, see Government Regulation—Regulation in the United States—Regulation of Product Marketing and Promotion. Outside the United States, we sell principally to healthcare providers and/or pharmaceutical wholesale distributors depending on the distribution practice in each country. In the Asia Pacific region, we also sell our products in partnership with other companies, including BeiGene, Daiichi Sankyo, KKC and Takeda.

Our product sales to three large wholesalers, McKesson Corporation, AmerisourceBergen Corporation and Cardinal Health, Inc., each individually accounted for more than 10% of total revenues for each of the years 2021, 2020 and 2019. On a combined basis, these wholesalers accounted for 82%, 83% and 81% of worldwide gross revenues for 2021, 2020 and 2019, respectively. We monitor the financial condition of our larger customers and limit our credit exposure by setting credit limits and, in certain circumstances, by requiring letters of credit or obtaining credit insurance.

Our products are marketed around the world, with the United States as our largest market. The following chart shows our product sales by principal product, and the table below (dollar amounts in millions) shows product sales by geography for the years 2021, 2020 and 2019.

Product Sales by Geography:

ENBREL

We market ENBREL, a tumor necrosis factor blocker, in the United States and Canada. ENBREL was launched in 1998 and is used primarily in indications for the treatment of adult patients with moderately to severely active rheumatoid arthritis, patients with chronic moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy and patients with active psoriatic arthritis.

Prolia

We market Prolia in many countries around the world. Prolia contains the same active ingredient as XGEVAbut is approved for different indications, patient populations, doses and frequencies of administration. Prolia was launched in the United States and Europe in 2010. In the United States, it is used primarily in the indication for the treatment of postmenopausal women with osteoporosis at high risk of fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or in patients who have failed or are intolerant to other available osteoporosis therapy. In Europe, Prolia is used primarily for the treatment of osteoporosis in postmenopausal women at increased risk of fracture.

Otezla

We market Otezla, a small molecule that inhibits PDE4, in many countries around the world. Otezla was acquired from BMS in November 2019 after their acquisition of Celgene. Otezla is an oral therapy approved for the treatment of adult patients with plaque psoriasis across all severities for whom phototherapy or systemic therapy is appropriate, patients with active psoriatic arthritis and patients with oral ulcers associated with Behçet’s disease. In Europe, Otezla is approved for second-line use in the treatment of psoriatic arthritis and psoriasis and for patients with oral ulcers associated with Behçet’s disease who are candidates for systemic therapy.

XGEVA

We market XGEVA in many countries around the world. XGEVA was launched in 2010 and is used primarily in the indication for prevention of SREs (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in patients with bone metastases from solid tumors and multiple myeloma.

Neulasta

We market Neulasta, a pegylated protein based on the filgrastim molecule, primarily in the United States and Europe. Neulasta was launched in 2002 and is used primarily in the indication to help reduce the chance of infection due to a low white blood cell count in patients with certain types of cancer (nonmyeloid) who receive anticancer medicines (chemotherapy) that can cause fever and a low blood cell count. In 2015, the Neulasta Onpro kit became available in the United States. The Neulasta Onpro kit provides physicians the opportunity to initiate administration of Neulastaon the same day as chemotherapy, with drug delivery of the recommended dose of Neulasta at home the day after chemotherapy, thereby saving the patient a trip back to the doctor.

Aranesp

We market Aranesp primarily in the United States and Europe. It was launched in 2001 and is indicated to treat a lower-than-normal number of red blood cells (anemia) caused by CKD in both patients on dialysis and patients not on dialysis. Aranesp is also indicated for the treatment of anemia due to concomitant myelosuppressive chemotherapy in certain patients with nonmyeloid malignancies and when chemotherapy will be used for at least two months after starting Aranesp.

Repatha

We market Repatha, a PCSK9 inhibitor, in many countries around the world. Repatha was launched in 2015 and is indicated to reduce the risks of myocardial infarction, stroke and coronary revascularization in adults with established CV disease. Repatha is also indicated to reduce LDL-C in adults with primary hyperlipidemia, including HeFH; in pediatric patients aged 10 years and older with HeFH; and in adults and pediatric patients aged 10 years and older with HoFH.

KYPROLIS

We market KYPROLIS primarily in the United States and Europe. KYPROLISwas launched in 2012 and is indicated in combination with (i) dexamethasone, (ii) lenalidomide plus dexamethasone and (iii) DARZALEX plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. It is also approved as a single agent for patients with relapsed or refractory multiple myeloma who have received one or more previous therapies.

Nplate

We market Nplate in many countries around the world. Nplate was launched in 2008 and is indicated to treat thrombocytopenia in patients with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.

Other Marketed Products

We also market a number of other products in various markets worldwide, including MVASI, Vectibix, KANJINTI, EVENITY, EPOGEN, BLINCYTO, AMGEVITA, Aimovig, Parsabiv, NEUPOGEN, LUMAKRAS/LUMYKRAS, Sensipar/Mimpara, AVSOLA, RIABNI and TEZSPIRE.

Patents

The following table lists our outstanding material patents for the indicated product by territory, general subject matter and latest expiry date. Certain of the European patents are subjects of supplemental protection certificates that provide additional protection for the products in certain European countries beyond the dates listed in the table. See footnotes to the patent table below.

One or more patents with the same or earlier expiry dates may fall under the same general subject matter and are not listed separately.

Product Territory General subject matter Expiration

U.S. Fusion protein and pharmaceutical compositions 11/22/2028

U.S. DNA encoding fusion protein and methods of making fusion protein 4/24/2029

Prolia®/XGEVA® (denosumab) U.S. Methods of treatment 6/25/2022

U.S. RANKL antibodies, including sequences 2/19/2025

Europe RANKL antibodies, including sequences(1) 6/25/2022

Otezla® (apremilast) U.S. Compositions and compounds 2/16/2028

Europe Compositions, compounds and methods of treatment(1) 3/20/2023

KYPROLIS® (carfilzomib) U.S. Compositions and compounds 12/7/2027

U.S. Methods of making 5/8/2033

Europe Compositions, compounds and methods of treatment(1) 12/7/2025

Repatha® (evolocumab) U.S. Antibodies(3) 10/25/2029

Europe Methods of treatment 5/10/2032

Nplate® (romiplostim) U.S. Formulation 2/12/2028

EVENITY® (romosozumab-aqqg) U.S. Antibodies(3) 4/25/2026

U.S. Formulation and methods of using formulation 5/11/2031

Europe Methods of treatment 4/18/2032

Europe Formulation and methods of using formulation 5/11/2031

U.S. Method of administration 9/28/2027

Europe Bifunctional polypeptides(1) 11/26/2024

Europe Method of administration 11/6/2029

Product Territory General subject matter Expiration

Aimovig® (erenumab-aooe) U.S. CGRP receptor antibodies 5/17/2032

Europe Methods of treatment 8/10/2035

Parsabiv® (etelcalcetide) U.S. Compound and pharmaceutical composition 2/7/2031

U.S. Methods of making 8/9/2035

Europe Compound and pharmaceutical composition(1) 7/29/2030

Europe Compounds, pharmaceutical compositions and methods of treatment 5/21/2038

TEZSPIRETM (tezepelumab-ekko) U.S. Polypeptides(3) 2/3/2029

(1)A European patent with this subject matter may also be entitled to supplemental protection in one or more countries in Europe, and the length of any such extension will vary by country. For example, supplementary protection certificates have been issued related to the indicated products for patents in at least the following countries:

•denosumab — France, Germany, Italy, Spain and the United Kingdom, expiring in 2025

•apremilast — Italy, Spain and the United Kingdom expiring in 2028

•carfilzomib — France, Germany, Italy, Spain and the United Kingdom expiring in 2030

•evolocumab — France, Spain and the United Kingdom, expiring in 2030

•romiplostim — France, Germany, Italy, Spain and the United Kingdom, expiring in 2024

•panitumumab — France, Germany, Italy, Spain and the United Kingdom, expiring in 2022

•romosozumab — France, Italy and Spain, expiring in 2031

•blinatumomab — France, Italy and Spain, expiring in 2029

•erenumab — France, Italy and Spain, expiring in 2033

•etelcalcetide — France, Germany, Italy, Spain and the United Kingdom, expiring in 2031

(2)U.S. Patent No. 10,092,541 was held invalid by the New Jersey District Court. We disagree with the court’s holding and we are in the process of appealing this judgment. See Part IV—Note 19, Contingencies and commitments, to the Consolidated Financial Statements, Amgen Inc. vs. Sandoz Inc., et al.

(3)A patent with this subject matter may be entitled to patent term extension in the United States.

Competition

We operate in a highly competitive environment. A number of our marketed products are indicated for disease areas in which other products or treatments are currently available or are being pursued by our competitors through R&D activities. Additionally, some competitor-marketed products target the same genetic pathways as our recently launched marketed products or are currently in development. This competition could impact the pricing and market share of our products. We continue to pursue ways of increasing the value of our medicines through innovations during their life cycles, which can include expanding the disease areas for which our products are indicated and finding new methods to make the delivery of our medicines easier and less costly. Such activities can offer important opportunities for differentiation. For example, we market the Neulasta Onpro kit, which provides physicians the opportunity to initiate administration of the recommended dose of Neulastaon the same day as chemotherapy, with drug delivery at home the day after chemotherapy, thereby saving the patient a trip back to the doctor. We plan to continue pursuing innovation efforts to strengthen our competitive position. Such position may be based on, among other things, safety, efficacy, reliability, availability, patient convenience, delivery devices, price, reimbursement, access to and timing of market entry and patent position and expiration.

Certain of the existing patents on our principal products have expired, and we face new and increasing competition, including from biosimilars and generics. A biosimilar is another version of a biological product for which marketing approval is sought or has been obtained based on a demonstration that it is “highly similar” to the original reference product. We have experienced adverse effects from biosimilar competition on our originator product sales. Companies have launched biosimilar versions of EPOGEN, NEUPOGEN and Neulasta and have approved biosimilars for ENBREL. Once multiple biosimilar versions of one of our originator products have launched, competition has intensified rapidly, resulting in greater net price declines for both reference and biosimilar products, and a greater effect on product sales. See also Government Regulation—Regulation in the United States—Approval of Biosimilars. Although competitor biosimilars compete on price, we believe many patients, providers and payers will continue to place high value on the reputation, supply reliability and safety of our products. As additional biosimilar competitors come to market, we will continue to leverage our global experience to distinguish against both branded and biosimilar competition.

We also have our own biosimilar products both in the United States and outside of U.S. markets that are competing against branded and biosimilar versions of our competitors’ products. In 2019, Amgen launched MVASI, a biosimilar to Avastin, and KANJINTI, a biosimilar to Herceptin; and in 2018, Amgen launched AMGEVITA, a biosimilar to Humira in ex-U.S. markets. We have also received FDA approval of AMJEVITA, a biosimilar to Humira for the U.S. market, and plan to launch in the United States in January 2023. In 2020, we launched AVSOLA, a biosimilar to Remicade;and in January 2021, we launched RIABNI, a biosimilar to Rituxan. We expect additional biosimilar competition against both our branded and biosimilar products in the future across markets.

Although most of our products are biologics, some are small molecule products. Because the FDA approval process permits generic manufacturers to rely on the safety and efficacy data of the innovator product rather than having to conduct their own costly and time-consuming clinical trials, generic manufacturers can often develop and market their competing versions of our small molecule products at much lower prices. For example, following loss of exclusivity of patents directed to cinacalcet, the active ingredient in our small molecule calcimimetic Sensipar, we lost a significant share of the market and corresponding revenues in a very short period of time. See Part IV—Note 19, Contingencies and commitments, to the Consolidated Financial Statements.

The introduction of new products, the development of new processes or technologies by competitors or the emergence of new information about existing products may result in (i) increased competition for our marketed products, even for those protected by patents and/or (ii) reductions in the prices we receive from selling our products. In addition, the development of new treatment options or standards of care may reduce the use of our products or may limit the utility and application of ongoing clinical trials of our product candidates. (As used in this document, the term clinical trials may include prospective clinical trials, observational studies, registries and other studies.) See Item 1A. Risk Factors—Our products face substantial competition and our product candidates are also likely to face substantial competition and Item 1A. Risk Factors—We currently face competition from biosimilars and expect to face increasing competition from biosimilars and generics in the future.

The following table reflects our significant competitors and is not exhaustive.

Product Territory Competitor-marketed product Competitors

ENBREL U.S. & Canada HUMIRA AbbVie

U.S. Xeljanz Pfizer Inc.

U.S. & Canada RINVOQ AbbVie

Prolia U.S. & Europe Alendronate, raloxifene and zoledronate generics Various

Otezla U.S. & Europe HUMIRA† AbbVie

U.S. & Europe Cosentyx Novartis

U.S. & Europe Taltz Lilly

U.S. & Europe Tremfya Janssen(1)

U.S. & Europe Skyrizi(2) AbbVie

U.S. & Europe Methotrexate generics Various

XGEVA U.S. & Europe Zoledronate generics Various

Neulasta(3) U.S. UDENYCA Coherus BioSciences, Inc.

U.S. Fulphila Mylan Institutional Inc.

U.S. & Europe Filgrastim biosimilars Various

Aranesp U.S. PROCRIT(4) Janssen(1)

U.S. & Europe Epoetin alfa biosimilars Various

Repatha U.S. & Europe PRALUENT Regeneron Pharmaceuticals, Inc.Sanofi

KYPROLIS(5) U.S. VELCADE Millennium Pharmaceuticals, Inc.(6)

U.S. & Europe REVLIMID Celgene(7)

U.S. & Europe POMALYST/IMNOVID Celgene(7)

U.S. & Europe DARZALEX Janssen(1)

Nplate U.S. & Europe PROMACTA/REVOLADE Novartis

† Approved biosimilars available in Europe and Canada.

(1)A subsidiary of J&J.

(2)Dermatology only.

(3)Other biosimilars under regulatory review in the United States and Europe.

(4)PROCRIT competes with Aranesp in supportive cancer care and predialysis settings.

(5)KYPROLIS is facing increased competition from several recently approved products.

(6)A subsidiary of Takeda.

(7)A subsidiary of BMS.

Reimbursement

Sales of our principal products are dependent on the availability and extent of coverage and reimbursement from third-party payers. In many markets around the world, these payers, including government health systems, private health insurers and other organizations, remain focused on reducing the cost of healthcare; and their efforts have intensified as a result of rising healthcare costs, economic pressures and broader challenges generated by the COVID-19 pandemic. Drugs remain heavily scrutinized for cost containment. As a result, payers are becoming more restrictive regarding the use of biopharmaceutical products and are scrutinizing the prices of these products while requiring a higher level of clinical evidence to support the benefits such products bring to patients and the broader healthcare system.These pressures become intensified when our products become subject to competition, including from biosimilars.

In the United States, healthcare providers and other entities such as pharmacies and PBMs are reimbursed for covered services and products they deliver through both private-payer and government healthcare programs such as Medicare and Medicaid. We provide negotiated rebates to healthcare providers, private payers, government payers and PBMs. In addition, we are required to (i) provide rebates or discounts on our products that are reimbursed through certain government programs, including Medicare and Medicaid, and (ii) provide discounts to qualifying healthcare providers under the federal 340B Drug Pricing Program.

Both private and some government payers use formularies to manage access to and utilization of drugs. A drug’s inclusion and favorable positioning on a formulary are essential to ensure patients have access to a particular drug. Even when access is available, some patients abandon their prescriptions for economic reasons. Payers continue to institute cost reduction and containment measures that lower drug utilization and/or spending altogether and/or shift a greater portion of the costs to patients. Such measures include, but are not limited to, more-limited benefit plan designs, higher patient co-pays or coinsurance obligations, limitations on patients’ use of commercial manufacturer co-pay payment assistance programs (including through co-pay accumulator adjustment or maximization programs), stricter utilization management criteria before a patient may get access to a drug, higher-tier formulary placement that increases the level of patient out-of-pocket costs and formulary exclusion, which effectively encourages patients and providers to seek alternative treatments or pay 100% of the cost of a drug. The use of such measures by PBMs and insurers has continued to intensify and has thereby limited Amgen product usage and sales. Furthermore, during the past few years, many PBMs and insurers have consolidated, resulting in a smaller number of PBMs and insurers overseeing a large portion of total covered lives in the United States. As a result, PBMs and insurers have greater market power and negotiating leverage to mandate stricter utilization criteria and/or exclude drugs from their formularies in favor of competitor drugs or alternative treatments. In highly competitive treatment markets such as the markets for ENBREL, Otezla, Repatha and Aimovig, PBMs are also able to exert negotiating leverage by requiring incremental rebates from manufacturers in order for them to gain and/or maintain their formulary position.

In addition to market actions taken by private and government payers in the United States, policy makers in both of the major U.S. political parties are pursuing policies to lower drug costs. Potential policies cover a wide range of areas, including allowing the importation of drugs from other countries; instituting IRP schemes, which would set the prices of certain drugs based on those available in other countries; implementing policies that in effect would require manufacturers to accept government-set prices for certain drugs, with price ceilings based on a domestic reference-pricing scheme; redesigning the Medicare Part D benefit so as to establish a cap on patient out-of-pocket costs, paired with new requirements that manufacturers cover a share of the costs of Part D drugs; stipulating penalties if drug price benchmarks rise faster than inflation; increasing transparency in drug pricing; and using third-party value assessments to determine drug prices. Examples of such policies include, but are not limited to, the previous Administration’s November 2020 interim final rule, which attempts to institute an MFN IRP model in Medicare Part B and a final rule instituting rebate reform in Medicare Part D. Both of the resulting rules are being challenged in court and have not yet been implemented. Further, although CMS withdrew the MFN IRP, policy makers continue to express strong interest in policies to address drug pricing. See Item 1A. Risk Factors—Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability. The Infrastructure Investment and Jobs Act signed into law on November 15, 2021, delays implementation of the rebate reform rule until 2026 and requires manufacturers of certain Part B–covered drugs packaged in single-use containers to give refunds to the government starting in 2023 for discarded amounts. Although the direction of drug-pricing-policy reforms remains unclear at this time, Congress is continuing to consider prescription-drug-pricing reforms, including legislative proposals for a number of the concepts discussed above (including a full repeal of the prior Administration’s Part D rebate reform rule).

In many countries other than the United States, government-sponsored healthcare systems are the primary payers for drugs and biologics. With increasing budgetary constraints and/or difficulty in understanding the value of medicines, governments and payers in many countries are applying a variety of measures to exert downward price pressure. These measures can include mandatory price controls, price referencing, therapeutic-reference pricing, increases in mandates, incentives for generic substitution and biosimilar usage and government-mandated price cuts. In this regard, many countries have health technology assessment organizations that use formal economic metrics such as cost-effectiveness to determine prices, coverage and reimbursement of new therapies; and these organizations are expanding in both established and emerging markets. Many countries also limit coverage to populations narrower than those specified on our product labels or impose volume caps to limit utilization. We expect that countries will continue taking aggressive actions to seek to reduce expenditures on drugs and biologics. Similarly, fiscal constraints may also affect the extent to which countries are willing to approve new and innovative therapies and/or allow access to new technologies. The EU is currently undergoing a review and possible revision of its pharmaceutical legislation, scheduled to conclude at the end 2022. There is a risk that this review will lead to proposals that may reduce intellectual property protection for new products, as well as change the reimbursement and regulatory landscape in ways that are difficult to predict at this point.

The dynamics and developments discussed above create pressures on the pricing and potential usage of our products and on the industry. Given the diverse interests in play between payers, biopharmaceutical manufacturers, policy makers, healthcare providers and independent organizations, if and whether the parties involved can achieve alignment on the matters discussed above remain unclear, and the outcome of any such alignment is difficult to predict. We remain focused on pricing our products responsibly and delivering breakthrough treatments for unmet medical needs. Amgen is committed to working with the entire healthcare community to ensure continued innovation and to facilitate patient access to needed medicines. We do this by:

•investing billions of dollars annually in R&D;

•pricing our medicines to reflect the value they provide;

•developing more affordable therapeutic choices in the form of high-quality and reliably supplied biosimilars;

•partnering with payers to share risk and accountability for health outcomes;

•providing patient support and education programs;

•helping patients in financial need access our medicines; and

•working with policy makers, patients and other stakeholders to establish a sustainable healthcare system with access to affordable care and in which patients and their healthcare professionals are the primary decision makers.

See Item 1A. Risk Factors—Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability and Item 1A. Risk Factors—Guidelines and recommendations published by various organizations can reduce the use of our products.

Manufacturing, Distribution and Raw Materials

Manufacturing

We believe we are a leader in the manufacture of biologics and that our manufacturing capabilities represent a competitive advantage. The products we manufacture consist of both biologics and small molecule drugs. The majority of our products are biologics that are produced in living cells and that are inherently complex due to naturally occurring molecular variations. Highly specialized knowledge and extensive process and product characterization are required to transform laboratory-scale processes into reproducible commercial manufacturing processes. Further, our expertise in the manufacture of biologics positions us well for leadership in the global biosimilars market. For additional information regarding manufacturing facilities, see Item 2. Properties.

We have been innovating our manufacturing facilities designed to extend our manufacturing advantage by optimizing our manufacturing network and/or by mitigating risks while continuing to ensure adequate supply of our products. For example, our licensed next-generation biomanufacturing plant operating in Singapore, and our recently FDA approved facility in West Greenwich, Rhode Island, incorporate multiple innovative technologies into a single facility. Next-generation biomanufacturing plants require smaller manufacturing footprints and offer greater environmental benefits, including reduced consumption of water and energy and lower levels of carbon emissions. Within such plants, the equipment is portable and smaller, which provides greater flexibility and speed in the manufacture of different medicines simultaneously. This enables Amgen to respond to changing demands for its medicines with increased agility. The Singapore site also has a plant that has been approved by several agencies, including the FDA and EMA, to produce small molecule drugs for commercial manufacturing.

Our internal manufacturing network has commercial production capabilities for bulk manufacturing, formulation, fill, finish, tableting and device assembly. These activities are performed within the United States and its territories in our Puerto Rico, Rhode Island and California facilities as well as internationally in our Ireland, Netherlands and Singapore facilities. In addition, we use third-party contract manufacturers to supplement the capacity or capability of our commercial manufacturing network.

To support our clinical trials, we manufacture product candidates primarily at our California facilities. We also use third-party contract manufacturers to supplement the capacity or capability of our overall clinical manufacturing network.

See Item 1A. Risk Factors for a discussion of the factors that could adversely impact our manufacturing operations and the global supply of our products.

Distribution

We operate distribution centers in Puerto Rico, Kentucky, California and the Netherlands for worldwide distribution of the majority of our commercial and clinical products. We also use third-party distributors to supplement distribution of our products worldwide.

Other

In addition to the manufacturing and distribution activities noted above, each of our manufacturing locations includes key manufacturing support functions such as quality control, process development, engineering, procurement, production scheduling and warehousing. Certain of those manufacturing and distribution activities are highly regulated by the FDA as well as international regulatory agencies. See Government Regulation—Regulation in the United States—Regulation of Manufacturing Standards.

Manufacturing Initiatives

As discussed above, we have been expanding capacity and advancing new innovations with multiple ongoing projects.

Our next-generation biomanufacturing plant at our West Greenwich, Rhode Island, campus, the first of its kind in the United States, received FDA approval in January 2022. This plant expands our capacity to manufacture certain products for U.S. and global markets, as we receive regulatory approval in those markets.

We initiated projects in 2019 to expand our clinical and commercial manufacturing capabilities in Thousand Oaks, California, which we have completed.

In August 2021, we initiated a project to build a new multi-product drug substance manufacturing facility in Holly Springs, North Carolina. The new plant will support both traditional stainless steel-fed batch manufacturing and next-generation single-use technologies, allowing flexibility in the production of multiple products in one plant.

In November 2021, we broke ground for our newest biomanufacturing plant located in New Albany, Ohio. This final product assembly and packaging plant will support the growing demand for Amgen’s medicines in the United States and will use state-of-the-art technologies.

See Item 1A. Risk Factors—Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product sales.

Raw Materials and Medical Devices

Certain raw materials, medical devices (including companion diagnostics) and components necessary for the commercial and/or clinical manufacturing of our products are provided by and are the proprietary products of unaffiliated third-party suppliers, certain of which may be our only sources for such materials. We currently attempt to manage the risk associated with such suppliers by means of inventory management, relationship management and evaluation of alternative sources when feasible. We also monitor the financial condition of certain suppliers and their ability to supply our needs. See Item 1A. Risk Factors—We rely on third-party suppliers for certain of our raw materials, medical devices and components.

We perform various procedures to help authenticate the sources of raw materials, including intermediary materials used in the manufacture of our products; the procedures include verification of country of origin and are incorporated into the manufacturing processes we and our third-party contract manufacturers perform.

To better ensure supply, Amgen has a risk mitigation strategy that uses a combination of methods, including multiple sources or backup inventory of critical raw materials. In response to the COVID-19 pandemic and as part of our ongoing business continuity efforts, we continue to closely monitor our inventory levels and have taken additional measures to mitigate against raw material supply interruption. See Item 1A. Risk Factors for a discussion of the factors that could adversely impact our manufacturing operations and the global supply of our products.

Government Regulation

Regulation by government authorities in the United States and other countries is a significant factor in the production and marketing of our products and our ongoing R&D activities. To clinically test, manufacture and market products for therapeutic use, we must satisfy mandatory procedures and safety and effectiveness standards established by various regulatory bodies. Compliance with these standards is complex, and failure to comply with any of these standards can result in significant implications. See Item 1A. Risk Factors for a discussion of factors, including global regulatory implications, that can adversely impact our development and marketing of commercial products.

Regulation in the United States

In the United States, the Public Health Service Act; the FDCA; and the regulations promulgated thereunder as well as other federal and state statutes and regulations govern, among other things, the production, research, development, testing, manufacture, quality control, labeling, storage, record keeping, approval, advertising, promotion and distribution of our products in addition to the reporting of certain payments and other transfers of value to healthcare professionals and teaching hospitals.

Clinical Development and Product Approval. Drug development in our industry is complex, challenging and risky, and failure rates are high. Product development cycles are typically very long—approximately 10 to 15 years from discovery to market. A potential new medicine must undergo many years of preclinical and clinical testing to establish its safety and efficacy for use in humans at appropriate dosing levels and with an acceptable risk–benefit profile. We continue to work toward reducing cycle times by applying our expertise in human genetics and innovation in technology, clinical trials and real-world evidence.

After laboratory analysis and preclinical testing in animals, we file an IND with the FDA to begin human testing. Typically, we undertake an FDA-designated three-phase human clinical testing program.

•In phase 1, we conduct small clinical trials to investigate the safety and proper dose ranges of our product candidates in a small number of human subjects.

•In phase 2, we conduct clinical trials to investigate side-effect profiles and the efficacy of our product candidates in a patient population larger than phase 1 but still relatively small, who have the disease or condition under study.

•In phase 3, we conduct clinical trials to investigate the short- and long-term safety and efficacy of our product candidates, compared to commonly used treatments, in a large number of patients who have the disease or condition under study.

The FDA monitors the progress of each trial conducted under an IND and may, at its discretion, reevaluate, alter, suspend or terminate the testing based on data accumulated to that point and the FDA’s risk–benefit assessment with regard to the patients enrolled in the trial. The results of preclinical and clinical trials are submitted to the FDA in the form of either a BLA for biologic products or a New Drug Application for small molecule products. We are not permitted to market or promote a new product until the FDA has approved our marketing application.

Approval of Biosimilars.The ACA authorized the FDA to approve biosimilars via a separate, abbreviated pathway. The pathway allows sponsors of a biosimilar to seek and obtain regulatory approval based in part on the nonclinical-trial and clinical-trial data of an originator product to which the biosimilar has been demonstrated to be “highly similar” and to have no clinically meaningful differences with regard to safety, purity and potency. The relevance of demonstrating “similarity” is that in many cases, biosimilars can be brought to market without conducting the full suite of clinical trials typically required of originators, because risk–benefit has previously been established. To preserve incentives for future innovation, the law establishes a period of exclusivity for originators’ products, which in general prohibits biosimilars from gaining FDA approval based in part on reliance on or reference to the originator’s data in their application to the FDA for 12 years after initial FDA approval of the originator product. The law does not change the duration of patents granted on biologic products. As part of the implementation of the abbreviated approval pathway for biosimilars, the FDA released a number of guidance documents, some of which remain in draft form.

Regulation of Product Marketing and Promotion. The FDA regulates the marketing and promotion of drug products. Our product promotions for approved product indications must comply with the statutory standards of the FDCA and the FDA’s implemented regulations and guidance. The FDA’s review of marketing and promotional activities encompasses but is not limited to direct-to-consumer advertising, healthcare-provider-directed advertising and promotion, sales representative communications to healthcare professionals, promotional programming and promotional activities involving electronic media. The FDA may also review industry-sponsored scientific and educational activities that make representations regarding product safety or efficacy in a promotional context. The FDA may take enforcement action against a company for promoting unapproved uses of a product or for other violations of the FDA’s advertising and labeling laws and regulations. Enforcement action may include product seizures, injunctions, civil or criminal penalties or regulatory letters, which may require corrective advertising or other corrective communications to healthcare professionals. Failure to comply with the FDA’s regulations also can result in adverse publicity or increased scrutiny of company activities by the U.S. Congress or other legislators. Additionally, as described below, such failure may lead to additional liability under U.S. healthcare fraud and abuse laws.

Regulation of Manufacturing Standards. The FDA regulates and inspects the equipment, facilities, laboratories and processes used in the manufacturing and testing of products prior to granting approval to market products. If after receiving approval from the FDA we make a material change in manufacturing equipment, location or process, additional regulatory review may be required. We also must adhere to current Good Manufacturing Practice regulations and product-specific regulations enforced by the FDA through its facilities inspection program. The FDA conducts regular, periodic visits to reinspect our equipment, facilities, laboratories and processes following an initial approval.

Regulation of Combination Products. Combination products are defined by the FDA as products composed of two or more regulated components (e.g., a biologic and/or drug and a device). Biologics/drugs and devices each have their own regulatory requirements, and combination products may have additional requirements. A number of our marketed products meet this definition and are regulated under this framework, and we expect that a number of our pipeline product candidates will be evaluated for regulatory approval under this framework as well.

Regulation outside the United States

In EU countries as well as in the United Kingdom, Switzerland, Canada, Australia and Japan, regulatory requirements and approval processes are similar in principle to those in the United States.

In the EU, there are currently two potential tracks for seeking marketing approval for a product not authorized in any EU member state: a decentralized procedure and a centralized procedure. In the decentralized procedure, identical applications for marketing authorization are submitted simultaneously to the national regulatory agencies. Regulatory review is led by one member state (the reference-member state), and its assessment—based on safety, quality and efficacy—is reviewed and approved (assuming there are no concerns that the product poses a serious risk to public health) by the other member states from which the applicant is seeking approval (the concerned-member states). The decentralized procedure leads to a series of single national approvals in all relevant countries. In the centralized procedure, which is required of all products derived from biotechnology, a company submits a single Marketing Authorisation Application to the EMA, which conducts an evaluation of the dossier, drawing upon its scientific resources across Europe. If the drug product is proven to fulfill requirements for quality, safety and efficacy, the EMA’s CHMP adopts a positive opinion, which is transmitted to the EC for final decision on granting of the marketing authorization. Even though the EC generally follows the CHMP’s opinion, it is not bound to do so. Subsequent commercialization is enabled by country-by-country reimbursement approval.

In the EU, biosimilars are approved under a specialized pathway of the centralized procedure. As with the U.S. pathway, an applicant seeks and obtains regulatory approval for a biosimilar once the data exclusivity period for the original reference product has expired, relying in part on the data submitted for the originator product together with data evidencing that the biosimilar is “highly similar” with regard to quality, safety and efficacy to the original reference product authorized in the European Economic Area.

Other countries such as Russia, Turkey and those in Latin America and the Middle East have review processes and data requirements similar to those of the EU and in some cases can rely on prior marketing approval from U.S. or EU regulatory authorities. The regulatory process in these countries may include manufacturing/testing facility inspections, testing of drug product upon importation and other domestic requirements.

In Asia Pacific, a number of countries such as China, Japan, South Korea and Taiwan may require local clinical-trial data for bridging purposes as part of the drug registration process in addition to global clinical trials, which can add to overall drug development and registration timelines. In most of the Asian markets, registration timelines depend on marketing approval in the United States or the EU. In some markets in Asia, such as China, Indonesia and Thailand, regulatory timelines can be less predictable. The regulatory process may also include manufacturing/testing facility inspections, testing of drug product upon importation and other domestic requirements. Countries such as Australia and Japan have more-mature systems that would allow for submissions under more-competitive time frames. With regard to biosimilars, several of these countries have pathways to register biosimilars (e.g., Australia, India, Singapore, South Korea and Taiwan), and biosimilar products are already present on the markets (e.g., Australia and South Korea).

In some countries, such as Japan and those in the EU, medical devices may be subject to regulatory regimes whereby manufacturers must establish that their medical devices conform to essential requirements set out in the law for the particular device category. For example, in the EU, with limited exceptions, medical devices placed on the market must bear the Conformité Européenne marking to indicate their conformity with legal requirements.

Postapproval Phase

After approval, we continue to monitor adverse events and product complaints reported following the use of our products through routine postmarketing surveillance and studies when applicable. We report such events to the appropriate regulatory agencies as required by local regulations for individual cases and aggregate reports. We proactively monitor (according to good pharmacovigilance practices) and ensure the implementation of signal detection, assessment and the communication of adverse events that may be associated with the use of our products. We also proactively monitor product complaints through our quality systems, which includes assessing our drug delivery devices for device complaints, adverse events and malfunctions. We may also be required by regulatory agencies to conduct further clinical trials on our marketed products as a condition of their approval or to provide additional information on safety and efficacy. Health regulators, including the FDA, have authority to mandate labeling changes to products at any point in a product’s life cycle based on new safety information or as part of an evolving label change to a particular class of products.

Health regulators, including the FDA, also have authority both before and after approval to require that a company implement a risk management program for a product to ensure that the benefits of the drug outweigh the risks. Each risk management program is unique and varies depending on the specific factors required. In the United States, such a risk management program is known as a REMS; and we currently have REMSs for Prolia, Nplateand BLINCYTO.

Other Regulation

We are also subject to various laws pertaining to healthcare fraud and abuse, including antikickback laws and false-claims laws. Antikickback laws make it illegal to solicit, offer, receive or pay any remuneration in exchange for or to induce the referral of business, including the purchase or prescribing of a particular drug that is reimbursed by a state or federal program. False-claims laws prohibit knowingly and willingly presenting or causing to be presented for payment to third-party payers (including Medicare and Medicaid) any claims for reimbursed drugs or services that are false or fraudulent, claims for items or services not provided as claimed or claims for medically unnecessary items or services. Violations of fraud and abuse laws may be punishable by criminal and/or civil sanctions, including fines and civil monetary penalties, as well as by the possibility of exclusion from federal healthcare programs (including Medicare and Medicaid). Liability under false-claims laws may also arise when violation of certain laws or regulations related to the underlying product (e.g., a violation regarding improper promotional activity or unlawful payments) contributes to the submission of a false claim.

On April 25, 2019, we entered into a settlement agreement with the DOJ and the OIG of the HHS to settle certain allegations related to our support of independent charitable organizations that provide patients with financial assistance to access medicines. Additionally, we entered into a corporate integrity agreement that requires us to both maintain a corporate compliance program and undertake a set of defined corporate integrity obligations for a period of five years. Due to the breadth of the statutory provisions and the absence of guidance in the form of regulations or court decisions addressing some of our practices, it is possible that in the future, our practices might be further challenged under antikickback or similar laws.

The FCPA prohibits U.S. corporations and their representatives from offering, promising, authorizing or making payments to any foreign government official, government staff member, political party or political candidate in an attempt to obtain or retain business abroad. The scope of the FCPA arguably includes interactions with certain healthcare professionals in many countries. Other countries have enacted similar anticorruption laws and/or regulations. Failure by our employees, agents, contractors, vendors, licensees, partners or collaborators to comply with the FCPA and other anticorruption laws and/or regulations could result in significant civil or criminal penalties.

We are subject to various laws and regulations globally with regard to privacy and data protection. These laws and regulations involve the collection, storage, handling, use, disclosure, transfer and security of personal data. The legislative and regulatory environments regarding privacy and data protection are continually evolving and developing because these issues are subjects of increasing amounts of attention in countries globally. For example, we are subject to the EU’s GDPR, which became effective on May 25, 2018, the California Consumer Privacy Act of 2018, which became effective on January 1, 2020 and China’s Personal Information Protection Law, which became effective on November 1, 2021. Other jurisdictions where we operate have enacted or proposed similar legislation and/or regulations. For example, the Virginia Consumer Data Protection Act and the Colorado Privacy Act are set to become effective on January 1, 2023, and July 1, 2023, respectively. Failure to comply with these laws could result in significant penalties.

Our business has been and will continue to be subject to various other U.S. and foreign laws, rules and regulations. See Reimbursement section above.

Research and Development and Selected Product Candidates

We focus our R&D on novel human therapeutics for the treatment of serious illness. We capitalize on our strengths in human genetics, novel biology and protein engineering. We leverage our biologic expertise and seek to choose the optimal modality for a drug target and disease. And we use cutting-edge science and technology to study subtle biological mechanisms in search of therapies that will improve the lives of those who suffer from diseases.

Our discovery research programs may therefore yield targets that lead to the development of human therapeutics delivered as large molecules, small molecules, other combination modalities or new modalities. We have reshaped our portfolio and have increasingly focused our efforts on human genetics when possible to enhance the likelihood of success.

Since early 2021, COVID-19 global vaccination efforts have been under way to control the pandemic. However, uncertainty remains as to the length of time required for vaccination of a meaningful portion of the population and as to the efficacy of such vaccinations on the trajectory of the pandemic. Challenges to vaccination efforts, new variants and other causes of virus spread may require governments to issue additional restrictions and/or order shutdowns in various geographies. As a result, we expect to see continued volatility for at least the duration of the pandemic as governments respond to current local conditions. With regard to our drug development activities, we are continuously monitoring COVID-19 infection rates, including changes from new variants; we are working to mitigate effects on future study enrollment in our clinical trials; and we are evaluating the impact in all countries where clinical trials occur. We remain focused on supporting our active clinical sites in their providing care for patients and in our providing investigational drug supply.

For the years ended December 31, 2021, 2020 and 2019, our R&D expenses were $4.8 billion, $4.2 billion and $4.1 billion, respectively.

We have major R&D centers in Thousand Oaks and San Francisco, California; Iceland; and the United Kingdom, as well as smaller research centers and development facilities globally. See Item 2. Properties.

Our clinical trial activities are conducted by both our internal staff and third-party contract clinical trial service providers. To increase the number and diversity of patients available for enrollment in our clinical trials, we have opened clinical sites and will continue opening clinical sites and enrolling patients in a number of geographic locations. See Government Regulation—Regulation in the United States—Clinical Development and Product Approval for a discussion of government regulation over clinical development. Also see Item 1A. Risk Factors—We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications.

Some of our competitors are actively engaged in R&D in areas in which we have products or in which we are developing product candidates or new indications for existing products. For example, we compete with other clinical trials for eligible patients, which may limit the number of available patients who meet the criteria for certain clinical trials. The competitive marketplace for our product candidates is greatly dependent on the timing of entry into the market. Early entry may have important advantages in gaining product acceptance, thereby contributing to a product’s eventual success and profitability. Accordingly, we expect that in some cases, the relative speed with which we can develop products, complete clinical testing, receive regulatory approval and supply commercial quantities of a product to the market will be important to our competitive position.

In addition to product candidates and marketed products generated from our internal R&D efforts, we acquire companies, acquire and license certain product and R&D technology rights and establish R&D arrangements with third parties to enhance our strategic position within our industry by strengthening and diversifying our R&D capabilities, product pipeline and marketed product base. In pursuing these R&D arrangements and licensing or acquisition activities, we face competition from other pharmaceutical and biotechnology companies that also seek to license or acquire technologies, product candidates or marketed products from those entities performing the R&D.

The following table shows a selection of certain of our product candidates by phase of development in our therapeutic areas of focus as of February 8, 2022, unless otherwise indicated. Additional product candidate information can be found on our website at www.amgen.com. (The website address is not intended to function as a hyperlink, and the information contained on our website is not intended to be a part of this filing.) The information in this section does not include other, nonregistrational clinical trials that we may conduct for purposes other than for submission to regulatory agencies for their approval of a new product indication.

We may conduct nonregistrational clinical trials for various reasons, including to evaluate real-world outcomes or to collect additional safety information with regard to the use of products.

Molecule Investigational indication

Phase 3 programs

AMJEVITA Interchangeability

Bemarituzumab GEJ adenocarcinoma

BLINCYTO Ph-negative B-cell precursor Acute lymphoblastic leukemia

EVENITY Male osteoporosis

KYPROLIS Weekly dosing for relapsed multiple myeloma

Nplate Chemotherapy-induced thrombocytopenia

Otezla Genital psoriasis

Repatha Cardiovascular disease

TEZSPIRE Chronic rhinosinusitis with nasal polypsSevere asthma

ABP 654 Investigational biosimilar to STELARA (ustekinumab)

ABP 938 Investigational biosimilar to EYLEA (aflibercept)

ABP 959 Investigational biosimilar to SOLIRIS (eculizumab)

Phase 2 programs

Efavaleukin alfa Systemic lupus erythematosusUlcerative colitis

Olpasiran Cardiovascular disease

Ordesekimab Celiac disease

Otezla Palmoplantar pustulosis

Rozibafusp alfa Systemic lupus erythematosus

Tarlatamab Small cell lung cancer

TEZSPIRE Chronic obstructive pulmonary diseaseChronic spontaneous urticaria

Phase 1 programs

Acapatamab Prostate cancer

Pavurutamab Multiple myeloma

Tarlatamab Small-cell lung cancer

AMG 119 Small-cell lung cancer

AMG 176 Hematologic malignancies

AMG 193 Solid tumors

AMG 199 Metastatic GEJ cancer

AMG 256 Solid tumors

AMG 330 Acute myeloid leukemia

AMG 340 Prostate cancer

AMG 404 Solid tumors

AMG 427 Acute myeloid leukemia

AMG 506 Solid tumors

AMG 509 Prostate cancer

AMG 609 Nonalcoholic steatohepatitis

AMG 650 Solid tumors

AMG 994 Solid tumors

Phase 3 Product Candidate Program Changes

As of February 2, 2021, we had 13 phase 3 programs. As of February 8, 2022, we continued to have 13 phase 3 programs, as regulatory approvals were received for three programs, four programs initiated phase 3 studies and one program was terminated. These changes are set forth in the following table.

Molecule Investigational indication Program change

Otezla Mild-to-moderate psoriasis Approved by the FDA

RIABNI Non-Hodgkin’s lymphoma Approved by the FDA

AMJEVITA Interchangeability Initiated phase 3 study

Bemarituzumab GEJ adenocarcinoma Initiated phase 3 study

TEZSPIRE Chronic rhinosinusitis with nasal polyps Initiated phase 3 study

Otezla COVID-19 Terminated

Phase 3 Product Candidate Patent Information

The following table describes our composition-of-matter patents that have been issued thus far for our product candidates in phase 3 development that have yet to be approved for any indication in the United States or the EU. Patents for products already approved for one or more indications in the United States or the EU but that are currently undergoing phase 3 clinical trials for additional indications have been previously described. See Marketing, Distribution and Selected Marketed Products—Patents.

Molecule Territory General subject matter Estimated expiration*

Bemarituzumab U.S. Polypeptides 2029

Europe Polypeptides 2029

* Patent expiration estimates are based on issued patents, which may be challenged, invalidated or circumvented by competitors. The estimates do not include any term adjustments, extensions or supplemental protection certificates that may be obtained in the future and thereby extend these dates. Corresponding patent applications are pending in other jurisdictions. Additional patents may be filed or issued and may provide additional exclusivity for the product candidate or its use.

Phases 3 and 2 Program Descriptions

The following provides additional information about selected product candidates that have advanced into human clinical trials.

AMJEVITA

AMJEVITA is a biosimilar to HUMIRA, which is a monoclonal antibody that inhibits binding of TNF-alpha to cell surface TNF receptor / TNF-alpha.

Bemarituzumab

Bemarituzumab is a monoclonal antibody that inhibits FGFR2b. It is being investigated for the treatment of advanced GEJ adenocarcinoma.

In April 2021, Amgen announced that the FDA had granted Breakthrough Therapy designation for bemarituzumab.

BLINCYTO

BLINCYTO is an anti-CD19 x anti-CD3 BiTE® molecule. It is being investigated in newly diagnosed adults age 40 and older with Ph negative B-Cell precursor ALL.

Efavaleukin alfa

Efavaleukin alfa is an IL-2 mutein Fc fusion protein. It is being investigated for the treatment of systemic lupus erythematosus and ulcerative colitis.

EVENITY

EVENITY is a monoclonal antibody that inhibits the action of sclerostin. It is being evaluated as a treatment for male osteoporosis. EVENITY is being developed in collaboration with UCB.

KYPROLIS

KYPROLIS is a small molecule proteasome inhibitor. It is being investigated for weekly dosing in combinations with lenalidomide and dexamethasone for relapsed multiple myeloma.

In December 2021, we announced that the FDA had approved the expansion of the KYPROLIS prescribing information to include its use in combination with DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.

LUMAKRAS/LUMYKRAS

LUMAKRAS is a KRAS G12C small molecule inhibitor. It is being investigated as treatment for a variety of solid tumors, including NSCLC, colorectal cancerand other solid tumor cancers.

In May 2021, we announced that the FDA had approved LUMAKRAS for the treatment of adult patients with KRAS G12C–mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy.

In November 2021, we announced that the EMA’s CHMP had adopted a positive opinion and recommended conditional marketing authorization of LUMYKRAS, known as LUMAKRAS in the United States, for the treatment of adults with advanced NSCLC with KRAS G12C mutation and who have progressed after at least one prior line of systemic therapy.

In January 2022, we announced that the EC had granted conditional marketing authorization for LUMYKRAS for the treatment of adults with advanced NSCLC with KRAS G12C mutation and who have progressed after at least one prior line of systemic therapy. We also announced that LUMAKRAS had been approved in Japan for the treatment of KRAS G12C-mutated positive, unresectable, advanced and/or recurrent NSCLC that has progressed after systemic anticancer therapy.

Nplate

Nplate is a TPO-RA. It is being investigated for the treatment of CIT.

Olpasiran

Olpasiran is an siRNA that lowers lipoprotein(a), also known as Lp(a). It is being investigated in phase 2 for the treatment of atherosclerotic CV disease.

Ordesekimab

Ordesekimab is a monoclonal antibody that inhibits the action of IL-15. It is being investigated for the treatment of celiac disease and is being developed in collaboration with Provention Bio, Inc.

Otezla

Otezla is a small molecule that inhibits PDE4. It is being investigated in phase 3 studies for the treatment of patients with moderate-to-severe genital psoriasis. It is being investigated in a phase 2 study for treatment of palmoplantar pustulosis.

In February 2021, we announced the submission of an sNDA to the FDA for the treatment of adults with mild-to-moderate plaque psoriasis who are candidates for phototherapy or systemic therapy.

In May 2021, we announced that the FDA had accepted for review our sNDA for the treatment of adults with mild-to-moderate plaque psoriasis who are candidates for phototherapy or systemic therapy. The FDA had set a PDUFA action date of December 19, 2021.

In December 2021, we announced that the FDA had approved the expanded indication for Otezla for the treatment of adult patients with plaque psoriasis, who are candidates for phototherapy or systemic therapy, across all severities.

Repatha

Repathais a human monoclonal antibody that inhibits PCSK9. It is being investigated as a treatment for atherosclerotic CV disease in high-risk patients with high LDL-C without prior heart attack or stroke.

Rozibafusp alfa

Rozibafusp alfa is a novel antibody-peptide conjugate that simultaneously blocks the BAFF and ICOSLactivity. It is being investigated as a treatment for systemic lupus erythematosus.

Tarlatamab

Tarlatamab is an HLE anti- DLL3 x anti-CD3 BiTE® molecule. It is being investigated for the treatment of small cell lung cancer.

TEZSPIRE

TEZSPIRE is a human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin. It is being evaluated in phase 3 studies as a treatment for severe asthma and chronic rhinosinusitis with nasal polyps. It is also being investigated in phase 2 studies as a treatment for chronic obstructive pulmonary disease and chronic spontaneous urticaria. TEZSPIRE is being developed jointly in collaboration with AstraZeneca.

In May 2021, we announced that our partner AstraZeneca had submitted a BLA to the FDA for tezepelumab, a potential first-in-class medicine in severe asthma.

In July 2021, we announced that the FDA had accepted a BLA and granted Priority Review of TEZSPIRE for the treatment of asthma.

In December 2021, we announced that the FDA had approved Amgen and AstraZeneca's TEZSPIRE for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.

In January 2022, we announced that TEZSPIRE is available for shipment to wholesalers in the United States.

AMG 451/KHK4083

AMG 451/KHK4083 is a monoclonal antibody that inhibits OX-40. It is being investigated for the treatment of moderate-to-severe atopic dermatitis. AMG 451/KHK4083 is being developed in collaboration with KKC.

ABP 654

ABP 654, a biosimilar candidate to STELARA(ustekinumab), is a monoclonal antibody that inhibits IL-12 and IL-23. It is being investigated in a phase 3 study for biosimilarity to STELARA. The reference-product primary conditions are psoriasis, psoriatic arthritis and Crohn’s disease.

ABP 938

ABP 938, a biosimilar candidate to EYLEA, is a VEGFR Fc fusion protein. It is being investigated in a phase 3 study for biosimilarity to EYLEA. The reference-product primary conditions are wet AMD, macular edema following retinal vein occlusion, diabetic macular edema and diabetic retinopathy.

ABP 959

ABP 959, a biosimilar candidate to SOLIRIS, is a monoclonal antibody that specifically binds to the complement protein C5. It is being investigated in a phase 3 study for biosimilarity to SOLIRIS. The reference-product primary conditions are PNH and aHUS.

Business Relationships

From time to time, we enter into business relationships, including joint ventures and collaborative arrangements, for the R&D, manufacture and/or commercialization of products and/or product candidates. In addition, we acquire product and R&D technology rights and establish R&D collaborations with third parties to enhance our strategic position within our industry by strengthening and diversifying our R&D capabilities, product pipeline and marketed-product base. These arrangements generally provide for nonrefundable, upfront license fees, development and commercial-performance milestone payments, cost sharing, royalty payments and/or profit sharing. The activities under these collaboration agreements are performed with no guarantee of either technological or commercial success, and each is unique in nature.

Trade secret protection for our unpatented confidential and proprietary information is important to us. To protect our trade secrets, we generally require counterparties to execute confidentiality agreements upon commencement of a business relationship with us. However, others could either develop independently the same or similar information or unlawfully obtain access to our information.

BeiGene, Ltd.

On January 2, 2020, we acquired a 20.5% stake in BeiGene for approximately $2.8 billion in cash as part of a collaboration to expand our oncology presence in China. Under the collaboration, BeiGene began selling XGEVA in 2020, BLINCYTO in 2021 and KYPROLIS in early 2022 in China, and Amgen shares profits and losses equally during the initial product-specific commercialization periods; thereafter, product rights may revert to Amgen, and Amgen will pay royalties to BeiGene on sales in China of such products for a specified period.

In addition, we jointly develop a portion of our oncology portfolio with BeiGene, which shares in global R&D costs by providing cash and development services of up to $1.25 billion. Upon regulatory approval, BeiGene will assume commercialization rights in China for a specified period, and Amgen and BeiGene will share profits equally until certain of these product rights revert to Amgen. Upon return of the product rights, Amgen will pay royalties to BeiGene on sales in China for a specified period. For product sales outside China, Amgen will also pay royalties to BeiGene.

Novartis

We are in a collaboration with Novartis to jointly develop and commercialize Aimovig. On January 31, 2022, concurrent with the settlement of the previously disclosed litigation between Amgen and Novartis we modified the terms of the collaboration. See Part IV—Note 19, Contingencies and commitments, to the Consolidated Financial Statements.

Arrangement through December 31, 2021

In the United States, Amgen and Novartis jointly developed and collaborated on the commercialization of Aimovig. Amgen, as the principal, recognized product sales of Aimovig in the United States, shared U.S. commercialization costs with Novartis and paid Novartis a significant royalty on net sales in the United States. Novartis held global co-development rights and exclusive commercial rights outside the United States and Japan for Aimovig (the ex-U.S. Novartis Rights). Novartis paid Amgen double-digit royalties on net sales of the product in the ex-U.S. Novartis Rights territories and funded a portion of global R&D expenses. In addition, Novartis was required to make a payment to Amgen of up to $100 million if certain commercial and expenditure thresholds were achieved with respect to Aimovig in the United States.

Arrangement after January 1, 2022

Pursuant to the amendment effective January 1, 2022, Novartis retains the ex-U.S. Novartis Rights and will continue to pay double-digit royalties on net sales in the ex-U.S. Novartis Rights territories. In the United States, Novartis will no longer collaborate with Amgen, share Aimovig commercialization costs or pay milestones and Amgen will no longer pay royalties to Novartis on sales of Aimovig. Amgen and Novartis will continue to share development expenses worldwide.

Amgen manufactures and supplies Aimovig worldwide.

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AMGN · 10-K · period ended 2021-12-31

Item 1. BUSINESS

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AMGN · 10-K · period ended 2021-12-31

Item 1. BUSINESS

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