Rituximab-arrx(Amgen, Inc.)

THOUSAND OAKS, Calif. , April 27, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced financial results for the first quarter of 2023. "We delivered 14% volume growth driven by the breadth of our portfolio and strong demand for our products globally," said Robert A. Bradway , chairman and chief executive officer. "We look forward to closing the acquisition of Horizon Therapeutics and joining forces to reach more patients around the world with their innovative medicines." Key results include: References in this release to "non-GAAP" measures, measures presented "on a non-GAAP basis," "free cash flow" (computed by subtracting capital expenditures from operating cash flow) and "total revenues and product sales adjusted for foreign exchange impact" (computed by converting our current period local currency product sales using the prior period foreign exchange rates and comparing that to our current period product sales) refer to non-GAAP financial measures. Adjustments to the most directly comparable GAAP financial measures and other items are presented on the attached reconciliations. Refer to Non-GAAP Financial Measures below for further discussion. Product Sales Performance Total product sales increased 2% for the first quarter of 2023 versus the first quarter of 2022. Unit volumes grew 14%, partially offset by 5% lower net selling price, 3% unfavorable changes to estimated sales deductions, 2% lower inventory levels and 2% negative impact from foreign exchange. General Medicine Inflammation Hematology-Oncology Established Products Product Sales Detail by Product and Geographic Region $Millions, except percentages Q1 '23 Q1 '22 YOY Δ US ROW TOTAL TOTAL TOTAL Repatha ® 197 191 388 329 18 % Prolia ® 623 304 927 852 9 % EVENITY ® 164 90 254 170 49 % Aimovig ® 64 5 69 101 (32 %) TEZSPIRE ® 96 — 96 7 * TAVNEOS ® 23 — 23 — NM Otezla ® 294 98 392 451 (13 %) Enbrel ® 564 15 579 862 (33 %) AMJEVITA ® /AMGEVITA ™ 51 113 164 108 52 % BLINCYTO ® 126 68 194 138 41 % Vectibix ® 111 122 233 201 16 % KYPROLIS ® 234 124 358 287 25 % LUMAKRAS ® /LUMYKRAS ™ 48 26 74 62 19 % XGEVA ® 384 152 536 502 7 % Nplate ® 246 116 362 266 36 % MVASI ® 121 81 202 244 (17 %) KANJINTI ® 33 14 47 96 (51 %) EPOGEN ® 60 — 60 120 (50 %) Aranesp ® 115 240 355 358 (1 %) Parsabiv ® 58 33 91 86 6 % Neulasta ® 211 38 249 348 (28 %) Other products** 152 41 193 143 35 % Total product sales $      3,975 $      1,871 $      5,846 $      5,731 2 % *Change in excess of 100% ** Other products include Corlanor ® , AVSOLA ® , NEUPOGEN ® , RIABNI ® , IMLYGIC ® and Sensipar ® /Mimpara ™ , as well as sales by Bergamo and GENSENTA subsidiaries. NM = not meaningful Operating Expense, Operating Margin and Tax Rate Analysis On a GAAP basis: On a non-GAAP basis: $Millions, except percentages GAAP Non-GAAP Q1 '23 Q1 '22 YOY Δ Q1 '23 Q1 '22 YOY Δ Cost of Sales $  1,720 $  1,561 10 % $  1,016 $    951 7 % % of product sales 29.4 % 27.2 % 2.2 pts 17.4 % 16.6 % 0.8 pts Research & Development $  1,058 $    959 10 % $  1,044 $    934 12 % % of product sales 18.1 % 16.7 % 1.4 pts 17.9 % 16.3 % 1.6 pts Selling, General & Administrative $  1,258 $  1,228 2 % $  1,224 $  1,213 1 % % of product sales 21.5 % 21.4 % 0.1 pts 20.9 % 21.2 % (0.3) pts Other $    148 $     (10) * $       — $       — NM Total Operating Expenses $  4,184 $  3,738 12 % $  3,284 $  3,098 6 % Operating Margin operating income as % of product sales 32.9 % 43.6 % (10.7) pts 48.3 % 54.8 % (6.5) pts Tax Rate 17.5 % 11.9 % 5.6 pts 17.8 % 14.1 % 3.7 pts pts: percentage points * change in excess of 100% NM = not meaningful Cash Flow and Balance Sheet $Billions, except shares Q1 '23 Q1 '22 YOY Δ Operating Cash Flow $       1.1 $       2.2 $    (1.1) Capital Expenditures $       0.3 $       0.2 $     0.2 Free Cash Flow $       0.7 $       2.0 $    (1.3) Dividends Paid $       1.1 $       1.1 $     0.1 Share Repurchases $        — $       6.3 $    (6.3) Average Diluted Shares (millions) 538 551 (13) Note: Numbers may not add due to rounding $Billions 3/31/23 12/31/22 YTD Δ Cash and Investments $     31.6 $       9.3 $   22.3 Debt Outstanding $     61.6 $     38.9 $   22.7 Note: Numbers may not add due to rounding 2023 Guidance (Excludes any contribution from the announced acquisition of Horizon Therapeutics plc) The Company expects the announced acquisition of Horizon Therapeutics plc (Horizon) to close in the first half of 2023. For the full year 2023, excluding any contribution from the announced acquisition of Horizon, the Company now expects: First Quarter Product and Pipeline Update The Company provided the following updates on selected product and pipeline programs: General Medicine Olpasiran (AMG 890) AMG 133 AMG 786 Repatha Prolia Aimovig Inflammation TEZSPIRE Rocatinlimab (AMG 451 / KHK4083) Rozibafusp alfa (AMG 570) Efavaleukin alfa (AMG 592) Ordesekimab (AMG 714 / PRV-015) Oncology BLINCYTO Tarlatamab (AMG 757) Bemarituzumab LUMAKRAS/LUMYKRAS Xaluritamig (formerly AMG 509) AMG 340 AMG 193 Biosimilars TEZSPIRE is being developed in collaboration with AstraZeneca. Rocatinlimab, formerly AMG 451 / KHK4083 is being developed in collaboration with Kyowa Kirin. Ordesekimab formerly AMG 714 and also known as PRV-015 is being developed in collaboration with Provention Bio. AMG 509 is being developed in collaboration with Xencor. Humira is a registered trademark of AbbVie, Inc. STELARA is a registered trademark of Janssen Pharmaceutica NV . EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc. SOLIRIS is a registered trademark of Alexion Pharmaceuticals, Inc. Non-GAAP Financial Measures In this news release, management has presented its operating results for the first quarters of 2023 and 2022, in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on a non-GAAP basis. In addition, management has presented its full year 2023 EPS and tax guidance in accordance with GAAP and on a non-GAAP basis. These non-GAAP financial measures are computed by excluding certain items related to acquisitions, divestitures, restructuring and certain other items from the related GAAP financial measures. Beginning January 1, 2022 , following industry guidance from the U.S. Securities and Exchange Commission , the Company no longer excludes adjustments for upfront license fees, development milestones and in-process research and development (IPR&D) expenses of pre-approval programs related to licensing, collaboration and asset acquisition transactions from its non-GAAP financial measures. GAAP financial measures are included in the news release. Management has presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the first quarter of 2023 and 2022. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP. Management has also presented Total Revenues and Product Sales Adjusted for Foreign Exchange Impact, which is a non-GAAP financial measure, for the first quarter of 2023. Total Revenues and Product Sales Adjusted for Foreign Exchange Impact is computed by converting our current period local currency product sales using the prior period foreign exchange rates and comparing that to our current period product sales. The Company believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. The Company uses certain non-GAAP financial measures to enhance an investor's overall understanding of the financial performance and prospects for the future of the Company's ongoing business activities by facilitating comparisons of results of ongoing business operations among current, past and future periods. The Company believes that FCF provides a further measure of the Company's liquidity. The Company believes Total Revenues and Product Sales Adjusted for Foreign Exchange Impact provides supplementary information on the Company's product sales performance by excluding changes in foreign exchange rates between comparative periods. The Company uses the non-GAAP financial measures set forth in the news release in connection with its own budgeting and financial planning internally to evaluate the performance of the business, including to allocate resources and to evaluate results relative to incentive compensation targets. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. About Amgen Amgen is 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 since 1980, 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 is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2022, Amgen was named one of the "World's Best Employers" by Forbes and one of "America's 100 Most Sustainable Companies" by Barron's. For more information, visit Amgen.com and follow us on Twitter, LinkedIn, Instagram, TikTok and YouTube. Forward-Looking Statements This news release 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., Kyowa-Kirin Co., Ltd., or any collaboration to manufacture therapeutic antibodies against COVID-19), the performance of Otezla ® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), the Five Prime Therapeutics, Inc. acquisition, the Teneobio, Inc. acquisition, the ChemoCentryx, Inc. acquisition, or the proposed acquisition of Horizon Therapeutics plc, 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 such as the ongoing COVID-19 pandemic 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 news release 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. 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. CONTACT: Amgen , Thousand Oaks Jessica Akopyan , 805-440-5721 (media) Arvind Sood , 805-447-1060 (investors) Amgen Inc. Consolidated Statements of Income - GAAP (In millions, except per-share data) (Unaudited) Three months ended March 31 , 2023 2022 Revenues: Product sales $    5,846 $    5,731 Other revenues 259 507 Total revenues 6,105 6,238 Operating expenses: Cost of sales 1,720 1,561 Research and development 1,058 959 Selling, general and administrative 1,258 1,228 Other 148 (10) Total operating expenses 4,184 3,738 Operating income 1,921 2,500 Other income (expense): Interest expense, net (543) (295) Other income (expense), net 2,064 (530) Income before income taxes 3,442 1,675 Provision for income taxes 601 199 Net income $    2,841 $    1,476 Earnings per share: Basic $      5.32 $      2.69 Diluted $      5.28 $      2.68 Weighted-average shares used in calculation of earnings per share: Basic 534 548 Diluted 538 551 Amgen Inc. Consolidated Balance Sheets - GAAP (In millions) March 31 , December 31 , 2023 2022 (Unaudited) Assets Current assets: Cash, cash equivalents and marketable securities $              31,561 $                9,305 Trade receivables, net 5,736 5,563 Inventories 5,011 4,930 Other current assets 2,395 2,388 Total current assets 44,703 22,186 Property, plant and equipment, net 5,460 5,427 Intangible assets, net 15,393 16,080 Goodwill 15,531 15,529 Other noncurrent assets 7,633 5,899 Total assets $              88,720 $              65,121 Liabilities and Stockholders' Equity Current liabilities: Accounts payable and accrued liabilities $              13,381 $              14,096 Current portion of long-term debt 834 1,591 Total current liabilities 14,215 15,687 Long-term debt 60,761 37,354 Long-term tax liabilities 5,864 5,757 Other noncurrent liabilities 2,532 2,662 Total stockholders' equity 5,348 3,661 Total liabilities and stockholders' equity $              88,720 $              65,121 Shares outstanding 534 534 Amgen Inc. GAAP to Non-GAAP Reconciliations (Dollars in millions) (Unaudited) Three months ended March 31 , 2023 2022 GAAP cost of sales $       1,720 $       1,561 Adjustments to cost of sales: Acquisition-related expenses (a) (669) (610) Certain net charges pursuant to our restructuring and cost savings initiatives (35) — Total adjustments to cost of sales (704) (610) Non-GAAP cost of sales $       1,016 $          951 GAAP cost of sales as a percentage of product sales 29.4 % 27.2 % Acquisition-related expenses (a) (11.4) (10.6) Certain net charges pursuant to our restructuring and cost savings initiatives (0.6) 0.0 Non-GAAP cost of sales as a percentage of product sales 17.4 % 16.6 % GAAP research and development expenses $       1,058 $          959 Adjustments to research and development expenses: Acquisition-related expenses (a) (14) (25) Non-GAAP research and development expenses $       1,044 $          934 GAAP research and development expenses as a percentage of product sales 18.1 % 16.7 % Acquisition-related expenses (a) (0.2) (0.4) Non-GAAP research and development expenses as a percentage of product sales 17.9 % 16.3 % GAAP selling, general and administrative expenses $       1,258 $       1,228 Adjustments to selling, general and administrative expenses: Acquisition-related expenses (a) (34) (15) Non-GAAP selling, general and administrative expenses $       1,224 $       1,213 GAAP selling, general and administrative expenses as a percentage of product sales 21.5 % 21.4 % Acquisition-related expenses (a) (0.6) (0.2) Non-GAAP selling, general and administrative expenses as a percentage of product sales 20.9 % 21.2 % GAAP operating expenses $       4,184 $       3,738 Adjustments to operating expenses: Adjustments to cost of sales (704) (610) Adjustments to research and development expenses (14) (25) Adjustments to selling, general and administrative expenses (34) (15) Certain net charges pursuant to our restructuring and cost savings initiatives (b) (141) (2) Certain other expenses (c) (7) 12 Total adjustments to operating expenses (900) (640) Non-GAAP operating expenses $       3,284 $       3,098 Three months ended March 31 , 2023 2022 GAAP operating income $       1,921 $       2,500 Adjustments to operating expenses 900 640 Non-GAAP operating income $       2,821 $       3,140 GAAP operating income as a percentage of product sales 32.9 % 43.6 % Adjustments to cost of sales 12.0 10.6 Adjustments to research and development expenses 0.2 0.4 Adjustments to selling, general and administrative expenses 0.6 0.2 Certain net charges pursuant to our restructuring and cost savings initiatives (b) 2.5 0.1 Certain other expenses (c) 0.1 (0.1) Non-GAAP operating income as a percentage of product sales 48.3 % 54.8 % GAAP interest expense, net $        (543) $        (295) Adjustments to interest expense, net: Interest expense on acquisition-related debt (d) 123 — Non-GAAP interest expense, net $        (420) $        (295) GAAP other income (expense), net $       2,064 $        (530) Adjustments to other income (expense), net: Interest income and other expenses on acquisition-related debt (d) (6) — Equity method investment basis difference amortization — 47 Net (gains)/losses from equity investments (e) (1,853) 365 Total adjustments to other income (expense), net (1,859) 412 Non-GAAP other income (expense), net $          205 $        (118) GAAP income before income taxes $       3,442 $       1,675 Adjustments to income before income taxes: Adjustments to operating expenses 900 640 Adjustments to interest expense, net 123 — Adjustments to other income (expense), net (1,859) 412 Total adjustments to income before income taxes (836) 1,052 Non-GAAP income before income taxes $       2,606 $       2,727 GAAP provision for income taxes $          601 $          199 Adjustments to provision for income taxes: Income tax effect of the above adjustments (f) (117) 189 Other income tax adjustments (g) (19) (4) Total adjustments to provision for income taxes (136) 185 Non-GAAP provision for income taxes $          465 $          384 GAAP tax as a percentage of income before taxes 17.5 % 11.9 % Adjustments to provision for income taxes: Income tax effect of the above adjustments (f) 1.0 2.3 Other income tax adjustments (g) (0.7) (0.1) Total adjustments to provision for income taxes 0.3 2.2 Non-GAAP tax as a percentage of income before taxes 17.8 % 14.1 % GAAP net income $       2,841 $       1,476 Adjustments to net income: Adjustments to income before income taxes, net of the income tax effect (719) 863 Other income tax adjustments (g) 19 4 Total adjustments to net income (700) 867 Non-GAAP net income $       2,141 $       2,343 Note: Numbers may not add due to rounding Amgen Inc. GAAP to Non-GAAP Reconciliations (In millions, except per-share data) (Unaudited) The following table presents the computations for GAAP and non-GAAP diluted earnings per share: Three months ended March 31, 2023 Three months ended March 31, 2022 GAAP Non-GAAP GAAP Non-GAAP Net income $        2,841 $        2,141 $        1,476 $        2,343 Weighted-average shares for diluted EPS 538 538 551 551 Diluted EPS $          5.28 $          3.98 $          2.68 $          4.25 (a) The adjustments related primarily to noncash amortization of intangible assets from business acquisitions. (b) For the three months ended March 31, 2023 , the adjustments related primarily to severance expenses associated with our restructuring plan initiated in early 2023. (c) For the three months ended March 31, 2023 , the adjustments related to the change in fair values of contingent consideration liabilities. For the three months ended March 31, 2022 , the adjustments related primarily to an in-process research and development asset adjustment. (d) For the three months ended March 31, 2023 , the adjustments included (i) interest expense and income 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 proposed acquisition of Horizon Therapeutics plc. (e) For the three months ended March 31, 2023 , the adjustments related primarily to our BeiGene, Ltd. equity fair value adjustment. (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, 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. Due to these factors, the effective tax rate for the adjustments to our GAAP income before income taxes for the three months ended March 31, 2023 , was 14.0% compared to 18.0% for the corresponding period of the prior year. (g) The adjustments related to certain acquisition items, prior period and other items excluded from GAAP earnings. Amgen Inc. Reconciliations of Cash Flows (In millions) (Unaudited) Three months ended March 31 , 2023 2022 Net cash provided by operating activities $     1,064 $     2,164 Net cash provided by (used in) investing activities 1,358 (111) Net cash provided by (used in) financing activities 21,509 (3,514) Increase (decrease) in cash and cash equivalents 23,931 (1,461) Cash and cash equivalents at beginning of period 7,629 7,989 Cash and cash equivalents at end of period $   31,560 $     6,528 Three months ended March 31 , 2023 2022 Net cash provided by operating activities $     1,064 $     2,164 Capital expenditures (344) (190) Free cash flow $       720 $     1,974 Amgen Inc. Reconciliation of Total Revenues and Product Sales Adjusted for Foreign Exchange (FX) Impact (Dollars in millions) (Unaudited) Three months ended March 31 , 2023 2022 Change FX impact $ (a) Three months ended March 31, 2023 excluding FX FX impact % (a) Change excluding FX Product Sales $       5,846 $       5,731 2 % $         (103) $        5,949 (2 %) 4 % Total Revenues $       6,105 $       6,238 (2 %) $         (103) $        6,208 (2 %) — % (a) Foreign exchange impact was calculated by converting our current period local currency Product sales using the prior period foreign exchange rates and comparing that to our current period Product sales. Amgen Inc Reconciliation of GAAP EPS Guidance to Non-GAAP EPS Guidance for the Year Ending December 31, 2023 (Unaudited) GAAP diluted EPS guidance $  15.38 — $ 16.59 Known adjustments to arrive at non-GAAP*: Acquisition-related expenses (a) 4.31 — 4.36 Net charges related to restructuring and cost savings initiatives 0.47 — 0.53 Net (gains)/losses from equity investments (2.70) Other 0.03 Non-GAAP diluted EPS guidance $  17.60 — $ 18.70 * The known adjustments are presented net of their related tax impact, which amount to approximately $0.48 - $0.50 per share. (a) The adjustments relate primarily to noncash amortization of intangible assets acquired in business acquisitions. Our GAAP diluted EPS guidance does not include the effect of GAAP adjustments triggered by events that may occur subsequent to this press release such as acquisitions, including any impact of the proposed Horizon acquisition, divestitures, asset impairments, litigation, changes in fair value of our contingent consideration obligations and changes in fair value of our equity investments. Reconciliation of GAAP Tax Rate Guidance to Non-GAAP Tax Rate Guidance for the Year Ending December 31, 2023 (Unaudited) GAAP tax rate guidance 17.0 % — 18.5 % Tax rate of known adjustments discussed above 0.5 % — 1.0 % Non-GAAP tax rate guidance 18.0 % — 19.0 % View original content to download multimedia: https://www.prnewswire.com/news-releases/amgen-reports-first-quarter-financial-results-301810090.html SOURCE Amgen

在政策方面，拜登政府在生物类似药领域降低药价、打击不正当竞争、专利诉讼和推动自动替换实施等方面的一系列举措极大的推动了生物类似药冲破重重阻碍的快速发展，极大的节省了政府在医药领域的巨额开支，政策层面的 整体概况 2022年全球生物药市场规模达到了4800亿美元，占到了全球医药整体市场规模的36%，预计将在五年后的2028年突破7000亿美元，进一步将份额提升至40%以上。近年来以欧美为首的的全球生物类似药市场保持飞速发展，稳步提升至近200亿美元的规模，随着以阿达木单抗为代表的一系列重磅产品生物类似药未来几年在欧美市场的全面上市，整体规模仍将进一步扩大，有望于2030年突破700亿美元。 2022年全球销售额TOP100药品中，单抗等生物大分子药物数量超过了一半。除去疫苗产品外，2022年全球销售额TOP20生物产品均为单抗和抗体融合蛋白；各产品全球销售额均在29亿美元以上，其中一半以上的产品收入在50亿美元以上；美国市场处于核心地位，TOP20中85%的产品美国市场收入在全球销售额中的占比在50%以上；产品主要分布在抗肿瘤和自体免疫领域，除奥瑞珠单抗和瑞莎珠单抗外的其他18个产品均已登陆中国市场；60%的产品在2010年之后获批，其中获批时间最早的依那西普距今已有近25年，获批最晚的瑞莎珠单抗距今仅有4年。 2022年全球销售额TOP20生物药原研产品（非疫苗类） 随着疫情影响的逐步减弱和消退，2022年美国医药市场整体规模（以发票金额计）再创新高，稳步提升至6300亿美元，蓬勃发展的生物药品在整体销售额中的占比达到了48%，预计将在2027年达到4000亿美元的规模，份额占比超过一半。 2022年美国生物类似药市场最终交出了75亿美元的答卷，10%的增速相比以往有所放缓，究其原因一方面在于之前已获批产品间竞争日渐加剧带来的价格持续下滑部分抵消了生物类似药不断渗透带来的增量正效应，另一方面个别产品的市场经过几年的洗牌在销量规模上已经日趋平衡甚至个别出现了萎缩，加之新上市产品普遍靠近年尾，对当年销售额的贡献比较有限。过去的一年里，首个眼科产品雷珠单抗华丽登场，成为上市的第九个新分子；非格司亭和贝伐珠单抗两个产品的生物类似药份额在万众瞩目中突破80%；Cimerli和Rezvoglar成功被授予可互换资格，进一步提振了生物类似药未来前进方向的信心；乌司奴单抗等一系列新产品如期进入申报环节，加速了步入新纪元的步伐；一切都是崭新的，目光所至、心之所向、以梦为名、不负荣光。 获批&上市 2022-2023美国生物类似药获批一览 （截至2月底） 从获批位次看，Coherus的Cimerli成为继三星的Byooviz之后第二个获批的雷珠单抗生物类似药，与之不同的是Cimerli在获批时就被FDA授予了可互换资格，继Cyltezo和Semglee之后第三个获此殊荣。Alymsys和Vegzelma成为第3和第4个获批的贝伐珠单抗生物类似药，Fylnetra和Stimufend成为第5和第6个获批的聚乙二醇化非格司亭生物类似药，Releuko作为第3个获批的非格司亭生物类似药，距离前面的二仿产品Nivestym获批已经过去了四年之久。 从审评时长看，Releuko由于一系列研发和现场检查中出现的质量问题前后历经4次CR才最终过关， 前后耗时1693天，前无古人后也很难再有来者；Fylnetra和Stimufend分别由于收到1次CR以及疫情影响下的现场检查延迟未能一轮过审，审评时长均超过了500天；Alymsys等四个产品顺利一轮通过，延续了贝伐珠单抗、阿达木单抗和雷珠单抗三个分子全部已获批生物类似药均在一个审评周期内获批的优良传统。 2022-2023年美国生物类似药上市一览（截至2月底） 截至目前，美国以351（K）途径申报的生物类似药获批总数量和上市数量已经分别达到了40个和27个。从产品类型看，共涉及维持治疗、抗肿瘤、自体免疫、胰岛素和眼科五大领域的11个分子，其中数量最多的阿达木单抗共有8个生物类似药获批，数量最少的阿法依泊汀只有1个生物类似药获批，曲妥珠单抗和聚乙二醇化非格司亭均以5个生物类似药上市的战绩成为当下竞争最为激烈的产品；从公司看，共涉及包括了原研创新型、专注研发型以及大型仿制药公司在内的12家公司，其中Pfizer以8个产品获批和6个产品上市的双第一战绩独占鳌头。获批未上市的13个生物类似药有9个受限于专利，其余则主要因为商业化策略暂未上市或放弃上市。 渗透&价格 美国市场生物类似药发展的大环境在过去的几年中不断改善，早期制约生物类似药发展的多重障碍被逐步剔除，法规层面对于原研公司通过不正当竞争谋求垄断的打击、使用环节医生和患者在培训推广助力下日益加深的理解、流通渠道PBM等核心参与方在目录制定等重要环节的开放以及生物类似药生产和销售方自身在药品质量、价格及便捷性等方面的不懈努力等多重因素共同推动了生物类似药“柳暗花明又一村”的破冰之旅。 在已上市生物类似药通过彼此之间以及与原研药的竞争不断拉低市场整体价格的大背景下，美国的医药支出得到了极大地节省，根据AAM报道，2021年涉及7大分子的全部生物类似药节省医药支出达到了70亿美元，并有望在未来五年实现累计节省支出突破千亿美元。随着生物类似药可互换资格的授予及全面应用以及阿达木单抗等多个重磅新产品生物类似药在未来几年的陆续上市，生物类似药的渗透将进一步增强并在节省开支方面发挥出更大的作用。 美国生物类似药历年节省医药费用一览 从具体数字看，截至2022年底，拥有生物类似药在市销售的7个产品的生物类似药（不含去年刚上市的雷珠单抗生物类似药和甘精胰岛素生物类似药Semglee）销量份额均在40%以上，其中贝伐珠单抗为首的罗氏抗肿瘤三件套以及早已实现财务自由的非格司亭四个产品生物类似药占比都突破了60%，7个分子中有6个在市生物类似药数量在3家及以上。 资历最老的非格司亭生物类似药自Zarxio上市经过七年多的发展将份额提高到创纪录的81%，成为了当下生物类似药销量占比最大的产品；竞争最为激烈的曲妥珠单抗生物类似药在去年将整体份额提升了14%，成为了2022年渗透幅度增长最大的产品；英夫利昔单抗、聚乙二醇化非格司亭和阿法依伯汀三个分子的原研产品通过采用跟进生物类似药同步降价的策略最大程度上减缓了竞争对手的强力渗透，依然保持着一半以上的市场份额，其对应的生物类似药整体销量份额被暂时限制在40%左右，共同成为渗透最慢的产品群。 从具体单品份额看，史上首个生物类似药Zarxio以60%的份额排名榜首，7个分子排名榜首的7个生物类似药中有5个为首仿产品，其中PEGG-CSF的首仿产品Fulfila以10%的份额排名全部首仿产品末尾。阿法依泊汀仅有的生物类似药Retacrit 2022年销量出现下滑，成为唯一一个2022年生物类似药整体份额未实现持续增长的分子。 2018-2022美国市场在市销售各分子生物类似药销量份额变化一览 Fresenius的聚乙二醇化非格司亭生物类似药于2023年2月上市，成为了目前在市生物类似药中最晚上市的产品，距离2015年9月上市的美国首个生物类似药Zarxio上市已有7年半之久，虽然不同分子生物类似药竞争产品数量和入市持续时长均有所不同，但都不同程度的通过竞争拉低了整体市场价格。7个分子当前最低产品ASP价格相比于生物类似药上市之前的原研品价格降幅在34%-77%之间，6个产品的降幅超过了60%。渗透时间最久的非格司亭以及拥有在市生物类似药产品数量最多的聚乙二醇化非格司亭的价格降幅最大，均达到了77%；近年来只有一家生物类似药在市销售的阿法依泊汀价格降幅最小，仅有34%。罗氏抗肿瘤三件套对应的生物类似药均于2019年才开始进入市场，但降价幅度均超过了60%。 原研公司在面临生物类似药竞争时的价格策略带来的二者之间的价格差直接决定着生物类似药渗透的速度，不同公司对待各自产品甚至同一公司对待自身不同产品的策略都不尽相同，以安进为例，其在已经江河日下的非格司亭原研产品Neupogen上任性的选择了放弃跟进，而在尚可背水一战的Neulasta上则理智的选择了步步紧跟，两种截然不同的态度也造就了两种大相径庭结果，非格司亭同时成为了原研与生物类似药价格差异最大和生物类似药渗透幅度最高的分子。 美国生物类似药涉产品价格变化一览 策略&管线 舞榭歌台，风流总被雨打风吹去。一曲笑傲江湖过后的余音仍在耳边缠绕，有人选择带着胜利昂首离开，刀剑入鞘、拂衣而去，只留下夕阳下山河渐远的黯淡背影；有人选择忘记伤痛继续前行，志在千里、壮心不已，纵死侠骨香的誓言响彻云间；有人选择快意恩仇仗剑天涯，初露锋芒、小试牛刀，那是欲与天公试比高的年少轻狂。 当下全球生物类似药的研发依然在如火如荼的高歌猛进，FDA2022财年末其生物类似药研发计划中包括的生物类似药项目已经达到了106个，共涉及30多个分子，其中20多个分子已有生物类似药进入美国临床阶段。20%的在研项目由全球年销售额在百亿美元以上的大公司开发，剩余80%的在研项目则由规模相对较小但具备相关经验的中小型公司开发。 随着近几年来美国生物类似药市场的不断成熟和完善，其未来发展的前景和轮廓日益清晰，各家公司在经历了早期或试水或观望的初级阶段后也在逐步结合自身实际情况开始调整策略。 Pfizer在2022年其生物类似药全球收入再次突破20亿美元（美国市场突破15亿美元），但比之新冠产品加持后创纪录的千亿销售额终究还是黯淡了不少，Pfizer目前依旧凭借着早期收购Hospira获得的多个生物类似药产品常年霸榜，但随着其逐步将重心转移至创新药的战略调整，生物类似药模块的权重大为下滑，内部已不再作为单列模块，除了今年即将上市的阿达木单抗外，后续研发管线已无其他生物类似药产品。 传统小分子仿制药三强Teva、Mylan和Sandoz作为首批试水者鏖战其中，时隔七年之后各自的未来已不尽相同，Teva和Sandoz依然坚持着自研加引进齐头并举的策略继续坚守着，在生物类似药领域实力更胜一筹的Sandoz在早期经验和产品红利逐步弱化的情况下开始加速外部合作，逐步走下坡路的Teva此时更是将生物类似药作为逆天改命的希望之一，Mylan在与Upjohn合并为Viatris后开始实施90亿美元的资产剥离计划，生物类似药首当其冲的被摆上货架交由亲密伙伴Biocon接盘，接下来女性健康、OTC和部分原料药业务也将被清理甩卖，Biocon接手后面临从幕后走上台前的角色转变， GMP合规方面已成为其当下最大的制约因素。 作为传统生物药研发生产型巨头的Celltrion和Samsung也是一直参与其中，Samsung在和Biogen分手后自主性和灵活性会更强，专注研发和生产的策略基本不会改变，Celltrion在美国小分子仿制药体验过独立销售后已经准备转战大分子领域，目前已经开始组建销售队伍，未来将在美国独立销售其自身产品。 Amneal、Fresenius和Hikma作为小分子仿制药领域的第二梯队开始在近年正式进军生物类似药领域，Amneal依托于和Kashiv的战略联盟以及自身创新药销售团队，目前已有两个产品在市销售，Fresenius凭借收购Merck生物类似药业务打下基础，刚刚通过顺利上市首个生物类似药Stimufend成功迈出了又一步，Hikma进场较晚但行动迅速，短期内仍需要凭借外力快速布局搭建轮廓。 预计最早上市时间表 生物类似药管线重点重叠产品概况一览 从具体产品看，致力于玩转美国市场的各路诸侯普遍持有多个处于临床III期至FDA审评阶段的产品，基本均为原研产品主要专利即将到期、美国市场销售额在20亿美元以上的重磅产品，产品线的相似性相对较高，多个产品出现了重叠，其中地舒单抗、阿柏西普和乌司奴单抗三大产品成为各方势力聚焦的重中之重，未来大概率出现十家以上竞争的白热化场面。临床阶段产品中以非格司亭为代表的一代目和以贝伐珠单抗为代表的的二代目已经比较罕见。 Teva当前生物类似药产品线共有12个产品组成，其中5个来自合作伙伴Alvotech，6个产品已处于临床至审评阶段，处于FDA审评中的阿达木单抗有望于今年4月成为首个获批并授予可互换资格的该分子高浓度产品，另一个在审重磅产品乌司奴单抗也有望于今年获批。地舒单抗和阿柏西普两个产品预计将于今年下半年完成III期临床。 作为最懂生物类似药的原研型公司，Amgen一直秉承在精不在多的发展理念。截至目前其生物类似药管线中的3个产品均已完成III期临床，其中乌司奴单抗已于去年三季度申报BLA，有望最早于今年首家上市，依库珠单抗和阿柏西普预计将于今年申报BLA，前者已经与原研公司Alexion达成和解，可于2025年3月登陆美国市场。 Sandoz近年来开始走外部引进为主以求提速和降低风险的路线，现有管线中与Polpharma、EirGenix、Bio-Thera和Gan&Lee四大伙伴合作的产品均已在近两年开花结果、完成了申报，自研的地舒单抗生物类似药也刚刚被FDA接受审评，领跑该产品其他竞争对手，其与Biocon在2018年达成的战略联盟也将在未来为其进一步丰富产品线。 Biocon于去年底完成了对Viatris生物类似药业务的收购，收回了多个此前授权转让出去的产品以及来自Momenta的阿柏西普生物类似药（首家美国申报），当前管线除了涵盖了地舒单抗等三大重磅产品外，还包括了其自身优势胰岛素领域的多个产品。本次收购使得Biocon在之前研发和生产能力的基础上获得了此前不具备的法规市场药政和销售资源，未来将实现一条龙的自给自足，当下最重要的乃是尽快解决掉制约在审产品获批的厂房GMP问题。 Celltrion四个处于III期临床的产品预计都将于今年内结束，Samsung当前剩余管线产品均处于待申报状态，两家公司的管线都涵盖了地舒单抗等三大重磅产品，Celltrion同Biocon一样也有望从今年起实现美国市场的研报产销一条龙；Samsung未来依然会专注于研发和生产，美国市场销售会继续由Organon和Biogen等合作伙伴负责。 Coherus于今年1月份引进了来自的Formycon的阿柏西普生物类似药，计划于今年申报BLA，面临当前产品线已经比较匮乏的情况，其将在未来几年内进一步加速引进处于研发末期的外部产品。Fresenius、Hikma和Lupin等此前以小分子仿制药见长的公司目前仍处于初期产线建立阶段，产品数量比较有限，通过实战积累各个环节的经验进而打牢根基是该时期最主要的目标。 诉讼进展 美国历年BPCIA诉讼数量 截至2022年底，美国累计BPCIA诉讼数量已经突破了50起，其中不乏一些双方针对同一产品在不同地区或针对不同专利发起的同源性诉讼。单年诉讼数量在申报潮的带动下在2018年达到顶峰，此后随着各家申报节奏的逐步放缓以及受疫情影响开始逐渐回落。过去的2022年里又有新的4起诉讼展开，2022年之前的诉讼已经全部了结，清零后第二战场的硝烟依然弥漫，似曾相识的画面中也多了些许不同寻常的新景。相比之前诉讼涉及阿达木单抗等9个已有生物类似药获批的分子，2022年的诉讼增加了阿柏西普、那他珠单抗和乌司奴单抗三个新分子，三起诉讼的被诉方均为首家申报该分子生物类似药的老熟人Mylan、Sandoz和Amgen，原告方相比之前增加了Regeneron和Biogen两张新面孔。另外一起针对老产品曲妥珠单抗的诉讼在Genentech和Tanvex之间，双方已在达成协议后和解。2022年和解的先前发起的诉讼主要针对聚乙二醇化非格司亭、贝伐珠单抗和阿达木单抗三个产品，诉讼历时均在300天以上，其中Nyvepria已在被诉后和解前冒险上市，另外两个产品目前尚未获批。 2022年美国已和解BPCIA诉讼 （2022年前申报）清单 2022年美国新发起BPCIA诉讼清单 从范围上看，2013年-2022年间在负责初审的地区法院层级总共由Amgen、Genetech、Janssen、AbbVie、Biogen和Regeneron六家原研药公司，针对目前有生物类似药获批的阿达木单抗等9个分子以及阿柏西普等目前尚未有生物类似药获批的3个新分子，向Celltrion等14家集团公司提起诉讼，共涉及30余个生物类似药（部分未获批）；从时间看，2017（11起）和2018（12起）两年成为诉讼发起最为集中的时间段，占据了全部诉讼数量的近一半，随后开始回落，近三年分别各有4、3和4起诉讼提出；从公司表现看，Amgen和Genetech以分别提出16起诉讼的数量并列排名原告第一，同时分饰两角的Amgen以承接9起诉讼的战绩排名被告第一，Celltrion和Sandoz以各被诉7起的数量并列排名被告第二。从耗时看，Sandoz的非格司亭生物类似药Zarxio和Celltrion的英夫利昔单抗生物类似药Inflectra从最初被诉到最终胜诉均历时近五年，成为拉锯时间最长的生物类似药产品，Sandoz的阿达木单抗生物类似药Hyrimoz从被诉到最终与原研和解仅历时2个月，成为诉讼耗时最短的产品；从结果看，近七成的诉讼最终以和解告终。 在BPCIA诉讼战场之外，更加快捷经济的无效专利程序也备受青睐，2022年美国各公司针对阿柏西普等多个产品共发起了15件IPR多方复审和2件PGR授权后复审，从具体产品看，曲妥珠单抗原研产品Herceptin、利妥昔单抗原研产品Rituxan和阿达木单抗原研产品Humira成为被挑战专利无效次数最多的产品；从被无效专利类型看，应用专利被挑战次数以绝对优势领先其他类型专利。 产品表现 原研产品/公司：Humira/AbbVie 美国获批时间：2002/12 Humira历年全球销售额一览 2022年，Humira在美国市场凭借着屡试不爽的涨价策略和销量持续的增长最终交出了186亿美元的答卷，创下历史新高的同时，美国市场收入在全球总收入中的占比继续提升至近19年来最高的87.7%。在销量突破1100万支的同时，注射笔包装形式和使用效果更佳的100mg/ml新处方产品份额分别进一步提升至90%和85%。 截至目前，在美申报该产品生物类似药的10家公司均已于AbbVie达成和解，其中8家公司的BLA已经获批。今年1月31日，首家获批并通过和解赢得最早上市时间的Amgen在历经2321天的漫长等待后正式在美上市了其阿达木单抗生物类似药产品Amjevita，吹响了生物类似药反击的号角。半年后将迎来第二波生物类似药的集体同步入市，其中Samsung Bioepis的Hadlima是目前唯一同时获批50mg/ml和100mg/ml两种规格的产品，BI的Cyltezo是目前唯一被FDA授予可互换资格的产品，Alvotech和Celltrion两家目前仍在审的产品仅涵盖了高浓度规格，前者的AVT02有望第二家被授予可互换资格，Sandoz则在去年补充申报了高浓度规格。目前包括AbbVie在内的各家公司均对自身产品持乐观态度，未来生物类似药的价格、可互换的实施程度以及高浓度规格产品的走势三大因素将协同作用最终决定2023年这场瞩目大战的胜负归属。 原研产品/公司：Avastin/Roche 美国获批时间：2004/02 Avastin历年全球销售额一览 2022年，原研产品Avastin美国市场销售收入为6.34亿瑞士法郎（约合6.67亿美元），下滑31%的同时，美国市场在近十年全球收入中的区域占比首次跌破30%。美国市场贝伐珠单抗的2020年整体销量达到了225万支（+5%），其中生物类似药占比历史性的提升至80%。Amgen的贝伐珠单抗首仿生物类似药Mvasi依然以近一半的份额占据销量榜首位置，但销售额受限于激烈竞争造成的价格下滑已下降至6.02亿美元（-27%）；Pfizer的Zirabev去年也实现了突破，通过抢占原研产品市场进一步提升至34%。 从规格看，100mg/4ml和400mg/16ml规格产品的差距不大，前者略占优势。整体市场价格进一步下滑，当前最低平均销售价格（来自Mvasi）已降至30美元/10mg，相当于原研品价格的45%。Amneal的Alymsys于去年10月上市，成为美国市场第三个上市的贝伐珠单抗生物类似药。 原研产品/公司：Herceptin/Roche 美国获批时间：1998/09 竞争难度：★★★★★ 冷星残月窗影摇，风自悲鸣雪自嘲。Herceptin以与Avastin近乎同样的陨落轨迹在过去的一年交出了21.42亿瑞士法郎（约合22.6亿美元）的答卷，欧美之外市场的进一步下滑加快了整体崩盘的进度，毫无悬念的迎来了巅峰之后的五连跌。 Herceptin历年全球销售额一览 原研产品/公司：Rituxan /Roche 美国获批时间：1997/11 Mabthera/Rituxan历年全球销售额一览 原研产品/公司：Neupogen/Amgen 美国获批时间：1991/02 Neupogen历年全球销售额一览 2022年，原研品Neupogen的美国市场销售额降至0.87亿美元（-14%），整体市场量约230万支，相比上年略有增长，其中预装注射器产品占比已经接近85%。从市场竞争来看，Amneal的Releuko于去年11月上市，打破了多年以来仅有两家严格意义上的生物类似药在市的局面。如果将Teva特殊时期的351(a)产品Granix包括在内，原研产品份额已不足20%，非格司亭成为当前渗透率最高的分子。Zarxio依旧以一半以上的份额领跑竞争，除在当前已上市生物类似药中上市时间最早外也是当前已上市生物类似药中份额比例最大的产品，Pfizer的Nivestym排名末尾。Amgen多年来坚持不降价策略硬磕到底，份额大幅流失，当前最低平均销售价格（来自Zarxio）已降至0.22美元/1mcg，相当于原研品价格的24%。 原研产品/公司：Neulasta/Amgen 美国获批时间：2002/01 Neulasta历年全球销售额一览 2022年Neulasta美国市场销售额降至9.59亿美元，在全球销售额中的占比依旧高达85%。130万支的市场总量保持稳定，其中目前只有原研品一家在售的自动注射器产品份额已经降至45%，占据另外55%份额的预装注射器产品之争在Amgen与Viatris、Coherus、Sandoz和Pfizer四家公司之间展开，Sandoz的三仿产品Ziextenzo通过大幅降价策略将预装注射器产品份额迅速提升至28%，微弱优势超越霸榜多年的Udenyca顺利登顶；Viatris的Fulfila原地踏步，成为目前表现不及预期的首仿生物类似药产品之一；Pfizer的Nyvepria沉沦依旧，价格太高真的很难卖动。尽管Amgen在Neulasta定价上紧随生物类似药步步跟进，但在大趋势下也仅能延缓份额的逐渐流失，将两种形式产品合并计算，生物类似药的份额已经由2018年刚进入市场时的1.3%提升至2022年的42%。当前最低平均销售价格（来自Ziextenzo）已降至1018美元/支，相当于原研品价格的67%，原研产品Neulasta与另外两个生物类似药Udenyca和Fulfila的价格持平。 Fresenius的Stimufend于今年2月进入市场，成为第五个上市的该产品生物类似药，聚乙二醇化非格司亭也与曲妥珠单抗并列成为了在市生物类似药数量最多的分子，Amneal已经获批的Fylnetra预计将于今年上半年上市，Lupin的该产品生物类似药目前处于FDA审评中，预计将于今年二季度获批。Coeherus和Fresenius已经申报了自动注射器版本的生物类似药，均有望于今年获批，其上市后各家价格的变化将直接决定未来市场竞争的走势。 7.依那西普（Etanercept） 原研产品/公司：Enbrel/Amgen 美国获批时间：2000/02 竞争难度：★★★★★ 一身转战三千里，一剑曾挡百万师。Amgen在完成美国的专利狙击后成功续命至2029年，缺少了生物类似药竞争的Enbrel并没有因此而高枕无忧。2022年，Enbrel在美国市场受流通渠道相关政策措施变化影响在销量和药价上都出现了下滑，由Pfizer负责的北美外市场在生物类似药的进一步渗透下同样步履蹒跚，两线均受挫导致全球销售额相比上年下滑了近10%，最终定格在51.2亿美元。 Enbrel历年全球销售额一览 2022年，Enbrel美国市场销售额降至40.44亿美元（-7%），占到了其全球销售额的79%，依然是Amgen当前的头号重磅产品，在Amgen全部单品销售额中占比为23%。美国市场整体销量约为650万支，粉针产品份额基本已消失殆尽，注射液产品包括了西林瓶、卡式瓶、预装注射器、自动注射笔四种包装形式，自动注射笔已经占到了68%的市场总量。 鉴于美国当前的专利障碍，已在欧盟和日本等全球多个市场实现上市的Lupin暂时已经不再计划进行美国申报，此前处于临床阶段的Coherus也已经停掉该项目，后续暂时已无其他新的潜在竞争对手在短期内寻求在美申报该产品。随着适应症重叠的阿达木单抗在今年迎来众多生物类似药的美国集体入市，Enbrel的美国市场销售预计将收到一定影响。 8.英夫利昔单抗（Infliximab） 原研产品/公司：Remicade/J&J 美国获批时间：1998/08 竞争难度：★★★☆☆ 待到来年九月八，我花开后百花杀。作为美国生物类似药发展史上的大事件之一，J&J与Pfizer历时四年的不正当竞争诉讼大战被载入史册。J&J此后通过降价策略继续围堵生物类似药，份额虽有丢失，但已是目前生物类似药渗透速率最慢的分子，原研产品的荣耀暂时得以捍卫。2022年，随着美国市场失手后的逐步沦陷，Remicade全球销售额降至29亿美元（-26%）。 Remicade历年全球销售额一览 2022年，Remicade美国市场销售额为16.21亿美元，在全球销售额中占比降至56%，相比上年下滑了28%，英夫利昔单抗美国整体市场销售量增加到了960万支，在逐渐回暖的形势下，生物类似药已经将整体份额由2020年的15.8%提升至41%。目前共有Pfizer/Inflectra、Organon/Renflexis以及Amgen/Avsola三家生物类似药在售，其中首仿产品Inflectra在过去一年中将份额提升28%，实现了2.89亿美元（-25%）的销售额，Renflexis和Avsola的销量份额占比均不足10%。生物类似药于2016年进入市场后带动了整体市场价格的持续下滑，当前生物类似药最低平均销售价格相比首仿上市时原研价格已经下降了70%，当前生物类似药最低平均销售价格（来自Inflectra）为23.4美元/10mg，相当于原研品价格的71%。 2022年底，Celltrion在美国完成了其皮下注射版英夫利昔单抗Remsima SC的申报，因原研无此形式产品参照，只能以351(a)形式申报BLA，未来该皮下注射版本将在Celltrion其现有在市产品Inflectra（合作伙伴Pfizer销售）的基础上进一步增添火力，此前该产品已在欧盟、加拿大和澳大利亚等多国获批后续暂时已无其他进展较快的潜在竞争对手在短期内寻求在美申报英夫利昔单抗生物类似药。 9.阿法依伯汀/依泊汀α（Epoetin Alfa） 原研产品/公司：Epogen&Procrit/Amgen 美国获批时间：1989/06 竞争难度：★★☆☆☆ 青山依旧在，几度夕阳红。现有生物类似药涉及分子原研产品中年龄最大的老将在坚持中再战一年，安进负责的美国市场部分2022年销售额降至5.06亿美元(-3%)，J&J负责的美国及全球其他市场部分因销售额过低已不在财报中单独列出，考虑到去年全球销售额已经跌至10亿美元以及下滑的整体趋势，推测2022年全球整体销售额在9-10亿美元之间，美国市场销售额在7亿美元左右。 Epogen/Procrit历年全球销售额一览 2021年时，阿法依伯汀美国市场销售额下降到了7.44亿美元（-15%），占到了全球销售额的74%，两个原研品牌产品Epogen（来自Amgen）和Procrit（来自J&J，Amgen授权）分别贡献了70%和30%。自Pfizer的生物类似药Retacrit于2018年底上市以来，一直未有新的生物类似药获批，2022年该产品的美国市场整体销量下滑至980万支，Retacrit的全年市场份额下降至42%，美国市场收入达到了3.12亿美元（-9%），占到了其全球销售额的79%。当前最低平均销售价格（来自Retacrit）已降至0.76美元/100units，与原研品价格基本持平。 暂时没有更多关于后续有计划在美国市场开发该产品生物类似药的其他公司的相关进展报道，两个原研品与一个生物类似药竞争的局面仍将继续维持下去。 11.甘精胰岛素（Insulin Glargine） 原研产品/公司：Lantus /Sanofi 美国获批时间：2000/04 竞争难度：★★★☆☆ 年年岁岁花相似，岁岁年年人不同。自原研产品Lantus在美由NDA化药转为BLA生物药已经过去了三年，在包括美国在内的多国政府通过多种举措降低胰岛素产品垄断和药价的努力下加之生物类似药产品的不断渗透，胰岛素产品的价格得到了有效的控制。2022年Lantus全球销售额已降至22.59亿欧元（折合25.7亿美元），迎来了自2016年以来的7连跌。 Lantus历年全球销售额一览 美国市场甘精胰岛素注射液各产品信息一览 Sanofi在Lantus之外于2015年推出了升级版本Toujeo，又在去年5月由其负责销售授权仿制药的子公司Winthrop上市了非品牌版本，本质上几个版本都属于生物品牌新药范畴；Viatris的Semglee在2020年胰岛素转为生物产品后以351(a)途径获批，其具有可互换资格的生物类似药于2021年7月获批，11月上市时同时推出了以Semglee为品牌的版本以及非品牌版本产品，两者均具有可互换资格，同时前述以351(a)途径获批的Semglee产品开始撤市退出舞台；Eli Lilly于2021年获批的甘精胰岛素生物类似药Rezvoglar已于去年底被授予可互换资格，截止目前还未上市，旗下仍有此前以化药获批并于2020年完成转换的的Basaglar在售。 去年11月，Viatris具有可互换资格的Semglee以及非品牌版本产品上市后份额相比之前明显提升，特别是在新病人群体中，2022年全年份额已经提升至10%（不含Basaglar）。比起其他已有生物类似药上市的分子而言，胰岛素领域相对比较特殊，更多的依赖于药房零售渠道，渠道各方的运作机制和相互关系更加复杂，具体自动替换的实施也收到产品是否被保险目录覆盖等多重因素的影响。政府对于降低胰岛素产品价格的努力仍在继续，近期拜登在国情咨文演讲中指出希望所有美国人的胰岛素价格上限为每月35美元，面对生物类似药来袭的Sanofi和Eli Lilly也分别采取了降价措施加以应对，未来的竞争将更加激烈。 美国市场甘精胰岛素各产品用药 来源分布及转换关系一览 Sandoz和Gan&Lee合作的甘精胰岛素生物类似药已经于今年2月被FDA接受审评；Lannett和HEC合作的产品目前处于临床数据分析中，预计将于2023年中申报BLA，有望于2024上半年在美上市；Civica在去年宣布与印度GeneSys Biologics合作共同开发甘精、赖脯和门冬三大胰岛素生物类似药的基础上，又分别选定Profil和Ypsomed两家欧洲公司分别作为临床及注射笔生产合作伙伴，产品有望于2024年上市。 12.雷珠单抗（Ranibizumab） 原研产品/公司：Lucentis/Roche 美国获批时间：2000/04 竞争难度：★★★☆☆ 爆竹声中一岁除, 春风送暖入屠苏。随着美国两个雷珠单抗生物类似药的相继上市，Lucentis在此前竞争压力主要来自于同领域其他创新药竞品及其生物类似药的基础上进一步加剧，美国市场历史性暴跌近30%使其全球销售额经历了上市以来的最大跌幅，最终以29亿美元（-19%）结束了2022年的征程。负责美国市场销售的Roche和美国外其他市场销售的Novartis分别贡献了其中的36%和64%。 Lucentis历年全球销售额一览 2022年Lucentis美国市场销售额为10.7亿美元(-25%)，市场总量下降至108万支(-17%)，预装注射器产品占到了总量的99%。Samsung Bioepis的雷珠单抗首仿产品Byooviz以及Coherus的二仿产品Cimerli先后于今年6月和10月上市，均为西林瓶装产品，因上市时间较短，四季度生物类似药份额仅有4%。当前Lucentis最新的平均销售价格为223美元/0.1mg，与生物类似药价格基本持平，相比Byooviz上市之前的自身价格已经下降了16%。 由Xbrane研发、Bausch + Lomb负责美国市场销售的雷珠单抗生物类似药Xlucane在去年撤回BLA后已补充修改完成，预计将于今年一季度完成再次申报。Lupin的LUBT010在完成III期临床后有望今年在美申报BLA。 未来展望 距离Zarxio获批已经过去了整整八年，从备受质疑、不被看好到举步维艰、困难重重，再从初露锋芒、小试牛刀到多点开花、捷报频传，美国生物类似药向阳而生、逆风而行，实现了一次次不同寻常的超越和突破。随着首个阿达木单抗生物类似药Amjevita在年初的顺利上市，2023年的群雄鏖战正式拉开了帷幕，悬念迭起、暗藏玄机、看点多多、期待满满。 在研发方面，目前针对美国市场的在研项目总数已经破百，研发涉及的大分子数量已有近40个，在纵向延伸的同时实现了横向拓展，在之前主要集中在抗肿瘤和自体免疫两大领域的基础之上进一步覆盖了眼科、胰岛素和骨健康等多个其他治疗领域。在以预计未来两年可以进入市场的乌司奴单抗等三大重磅产品为代表的的第三波生物类似药的研发争夺战已经进入末期，针对未来十年后可以进入市场的第四波生物类似药的研发也已初步开启，经过八年的洗礼与积淀，各家公司在策略明确的同时均针对性的进行了剥离或补强，圈子里的各路诸强在一番洗牌和资源整合之后彼此之间的实力差距已经愈发缩小。天下武功，唯快不破，在建立在研发硬实力之上的速度为先基础上，覆盖成本、质量和供应链等多环节的综合实力将最终决定成败归属，做得快很重要，但也要做得稳和准。 在注册方面，随着疫情阴霾的逐渐消散，FDA的海外现场检查将逐渐恢复常态，此前多个海外生产的生物类似药产品因为审计推迟导致批准延期的经历或再鲜有出现。随着乌司奴单抗、托珠单抗等一系列新分子生物类似药于去年的申报，今年已获批生物类似药涉及分子数量或将突破15个，改变多年来九大分子之外新增分子数量增长缓慢的局面。新的一年里将实施BsUFAIII（生物类似药用户付费法案）在授权后新的生物类似药开发各项目收费，2023财年生物类似药申请费和项目费用仍旧保持与上一财年持平，生物类似药产品开发费(BPD)再次下调，其中的初始BPD费、年度BPD费用和再激活费用均下降了17.2%。 在流通方面，生物类似药的自动替换已经在眼科和胰岛素产品领域开始实施并取得了一定的成效，Semglee作为先驱者试水也带动了后续生物类似药对于可互换资格申请的热潮。今年多个阿达木单抗生物类似药产品的集体上市将进一步检验自动替换在流通层面的实施效果并洞察保险公司、PBM等渠道中的多方策略的最新变化。随着过去一年雷珠单抗生物类似药的正式上市，眼科这一特殊领域对于生物类似药的认可和接受程度相比此前也得到了明显的提高，新的一年里各大分子生物类似药的渗透将进一步增强。 在竞争方面，降价潮在过去一年里席卷了多个产品，随着竞争的逐步加剧和日趋常态化，价格杠杆调节将被更多的运用到大分子领域生物类似药之间以及与原研产品的抗衡中。在价格因素之外，生物类似药也在不断努力冲破原研公司在产品差异化升级方面设置的重重障碍，Coherus的自动注射器生物类似药产品以及Alvotech为代表的的多个高浓度阿达木单抗产品的问世都是此类变化的典型代表。在被动应战之外，部分生物类似药也选择了更加积极的主动出击，Celltrion的皮下注射版英夫利昔单抗完美的诠释了专业之上极致研发的魅力。 在政策方面，拜登政府在生物类似药领域降低药价、打击不正当竞争、专利诉讼和推动自动替换实施等方面的一系列举措极大的推动了生物类似药冲破重重阻碍的快速发展，极大的节省了政府在医药领域的巨额开支，政策层面的持续助力仍将继续，为生物类似药发展大环境的日益完善贡献力量。