Denosumab biosimilar(Teva Pharma)

Teva delivers 3 consecutive years of growth - 2025 revenues of $17.3 billion, an increase of 4% year-over-year (YoY) in U.S. dollars, or 3% in local currency (LC) terms, compared to 2024. Excluding Japan BV, revenues increased 5% YoY in LC.Key Innovative brands continued to drive growth and provide value for patients, with 2025 revenues surpassing $3 billion, +35% YoY in LC: AUSTEDO® global revenues of $2.26 billion, growing 34% YoY in LC. AJOVY® global revenues of $673 million, up 30% YoY in LC.UZEDY® revenues of $191 million, up 63% YoY in LC; underscoring Teva's commitment to drive new advances in neuroscience: Fastest growing long-acting injectable (LAI)1FDA expanded indication approval for Bipolar 1 Disorder. Q4 2025 marks the first quarter in which these key brands collectively delivered ~$1 billion of revenues. Generics portfolio stable: Increased by 2% in the U.S., decreased by 2% in Europe and decreased by 2% in International Markets, all in LC terms compared to 2024. Excluding Japan BV, revenues increased by 1% in International Markets in LC, compared to 2024. Biosimilars pipeline and portfolio fueling growth: – with the second-largest portfolio and most biosimilars launched across the industry since 2020.2 Innovative late-stage pipeline continued to drive transformation: 4 innovative product submissions targeted over the next 5 years.Up to $500 million in funding secured via Teva’s agreement with Royalty Pharma to fund the development of anti-IL-15 (TEV-’408) for vitiligo indication.duvakitug (anti-TL1A) Phase 3 initiated for ulcerative colitis and Crohn's disease.Preparing for olanzapine LAI U.S. launch, subject to regulatory approval; New Drug Application (NDA) submitted to FDA in December 2025.FDA fast track designations for emrusolmin for Multiple System Atrophy and anti-IL-15 for Celiac disease. Transforming and modernizing our business through Teva Transformation programs – combined with innovative product growth, expected to achieve 30% non-GAAP operating income margin by 2027. On track to deliver ~$700 million of net savings by 2027; In 2025, achieved $70 million savings and expect to realize two-thirds of the targeted savings by 2026. Q4 and FY 2025 Highlights: Q4 2025 FY 2025 Revenues $4.7 billion $17.3 billion GAAP diluted earnings per share $0.41 $1.21 Non-GAAP diluted EPS $0.96 $2.93 Cash flow generated from operating activities $1,158 million $1,649 million Free cash flow $1,298 million $2,396 million 2026 Business Outlook: Revenues of $16.4 - $16.8 billionNon-GAAP operating income of $4.55 - $4.8 billionAdjusted EBITDA of $5.0 - $5.3 billionNon-GAAP diluted EPS of $2.57 - $2.77Free cash flow of $2.0 - $2.4 billion TEL AVIV, Israel, Jan. 28, 2026 (GLOBE NEWSWIRE) -- Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today reported results for the year and the quarter ended December 31, 2025. Mr. Richard Francis, Teva's President and CEO, said: “In 2025, our Pivot to Growth strategy drove Teva's third year of consecutive growth, solidifying our transformation into a leading biopharmaceutical company. Our key innovative brands led our growth, reaching $1 billion in revenues in the fourth quarter of 2025 for the first time, and becoming a true engine of sustainable growth. Throughout the year, our teams executed with discipline across the business, driving momentum in innovative medicines, scaling our global generics and biosimilars portfolio, and further optimizing our operations and capital allocation. We also continue to make progress on our deleveraging, in line with our 2027 targets.” Mr. Francis continued: “Looking ahead, 2026 will be a milestone-rich year with multiple late-stage pipeline readouts across immunology and neurology; the anticipated FDA approval of olanzapine LAI, and important data expected for duvakitug, our anti-TL1A, and for our anti-IL-15 programs. Together, these pipeline assets represent a potential of over $10 billion, reinforcing our confidence in Teva’s ability to deliver durable, innovation-driven growth, creating real value for patients and shareholders alike." Pivot to Growth Strategy In 2025, we continued to execute on the four key pillars of our “Pivot to Growth” strategy, which we announced in May 2023. Delivering on our growth engines - We continued to showcase strong performance of our key innovative brands, mainly AUSTEDO, AJOVY, and UZEDY collectively, +35% YoY in revenues for 2025. During 2025, the FDA approved an expansion of AJOVY's indication, to include its use as an anti-CGRP preventive treatment for pediatric episodic migraine, as well as an expansion of UZEDY as treatment for adults living with Bipolar 1 Disorder. Stepping up innovation - We continued to accelerate the development of certain key pipeline assets. Teva submitted a New Drug Application for olanzapine LAI to the FDA in December 2025, and during the year we received FDA fast track designations for both emrusolmin in MSA and our IL-15 (TEV-‘408) for Celiac Disease. Phase 3 programs for duvakitug (anti-TL1A) in ulcerative colitis and Crohn's disease were initiated, and Teva is working with its partner Sanofi on targeting additional indications. By the end of 2025, we achieved the targeted initial enrollment for adult and pediatric populations for DARI’s (Dual-action Asthma Rescue Inhaler) Phase 3 trial. In January 2026, we announced a funding agreement to accelerate the development of anti-IL-15 (TEV-‘408) for vitiligo with Royalty Pharma.Sustaining our generics powerhouse - We continued to optimize our generics business and build a strong pipeline of biosimilars; For biosimilars, we launched SELARSDITM (ustekinumab-aekn) the biosimilar to Stelara® and EPYSQLI®(eculizumab-aagh) the biosimilar to Soliris®, and also received EMA approvals for PONLIMSI® (denosumab) the biosimilar to Prolia® and DEGEVMA® (denosumab) the biosimilar to Xgeva®.Focusing our business - We are actively transforming and modernizing our business through Teva Transformation programs. On May 7, 2025, we announced that these programs are expected to generate ~$700 million of net savings through 2027. In 2025, we achieved $70 million in savings and expect to realize two-thirds of the targeted savings by 2026. We continued to optimize our portfolio and global manufacturing footprint. In addition, we continue our deleveraging efforts, reducing our gross debt levels to $16.8 billion and net debt to $13.3 billion through cash flow, repayment and refinancing, and optimizing our working capital management. In response to our improved capital structure and stronger underlying performance, our credit ratings were upgraded by one level at three credit ratings agencies in 2025. 2025 Annual Consolidated Results Revenues in 2025 were $17,258 million, an increase of 4% in U.S. dollars, or 3%, in local currency terms, compared to 2024. This increase was mainly due to higher revenues from our key innovative products AUSTEDO, AJOVY and UZEDY and from development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), partially offset by lower revenues from our International Markets segment due to the divestment of our business venture in Japan, from certain other innovative products across all our segments, lower proceeds from the sale of certain product rights, and from generic products in our Europe segment. Exchange rate movements during 2025, net of hedging effects, positively impacted revenues by $152 million and negatively impacted both operating income and non-GAAP operating income by $48 million, each as compared to 2024. Gross profit was $8,938 million in 2025, an increase of 11% compared to 2024. Gross profit margin was 51.8% in 2025, compared to 48.7% in 2024. Non-GAAP gross profit was $9,647 million in 2025, an increase of 9% compared to 2024. Non-GAAP gross profit margin was 55.9% in 2025, compared to 53.3% in 2024. This increase in both gross profit margin and non-GAAP gross margin was mainly due to a favorable mix of products, primarily driven by higher revenues from AUSTEDO, and development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), partially offset by lower proceeds from the sale of certain product rights. Research and Development (R&D) expenses, net in 2025 were $1,013 million, an increase of 2% compared to $998 million in 2024. Our higher R&D expenses, net in 2025 compared to 2024, were mainly due to an increase in immunology and in immuno-oncology, as well as in neuroscience (mainly neurodegeneration), partially offset by the non-recurrence of milestone payments related to certain biosimilar projects and lower expenses related to generics projects. Selling and Marketing (S&M) expenses in 2025 were $2,686 million, an increase of 6% compared to 2024. This increase was mainly to support revenue growth in our innovative portfolio, primarily AUSTEDO, and due to a negative impact from exchange rate fluctuations. General and Administrative (G&A) expenses in 2025 were $1,287 million, an increase of 11% compared to 2024. This increase was mainly due to costs related to optimization activities of our global organization and operations in connection with our Transformation programs, as well as a negative impact from exchange rate fluctuations. Operating Income was $2,157 million in 2025, compared to an operating loss of $303 million in 2024. Operating Income as a percentage of revenues was 12.5% in 2025, compared to an operating loss as a percentage of revenues of 1.8% in 2024. This change was mainly due to the goodwill impairment charges incurred in 2024, and in 2025, due to lower other asset impairment, restructuring and other items, as well as higher gross profit and lower legal settlements and loss contingencies in 2025. Non-GAAP operating income was $4,905 million in 2025, or 28.4% of revenues compared to $4,329 million, or 26.2% of revenues in 2024. The increase in non-GAAP operating margin was mainly affected by higher non-GAAP gross profit margin, as discussed above. In 2025, financial expenses, net were $934 million, compared to $981 million in 2024. Financial expenses in 2025 were mainly comprised of net-interest expenses of $824 million. Financial expenses in 2024 were mainly comprised of net-interest expenses of $915 million. In 2025, we recognized a tax benefit of $180 million on a pre-tax income of $1,223 million. In 2024, we recognized a tax expense of $676 million on a pre-tax loss of $1,284 million. Our effective tax rate for 2025 was the result of a variety of factors, including the geographic mix and type of products sold during the year, different effective tax rates applicable to non‐Israeli subsidiaries that have tax rates different than Teva’s average tax rate, adjustments to valuation allowances on deferred tax assets, adjustments to uncertain tax positions and net deferred tax benefits from intellectual property related integration plans. Non-GAAP tax rate for 2025 was 15.8%, compared to 15.3% in 2024. Our non-GAAP tax rate for 2025 was the result of a variety of factors, including the geographic mix and type of products sold during the year, different effective tax rates applicable to non‐Israeli subsidiaries that have tax rates different than Teva’s average tax rate, adjustments to valuation allowances on deferred tax assets, adjustments to uncertain tax positions and net deferred tax benefits from intellectual property related integration plans. Net income attributable to Teva and diluted earnings per share in 2025 were $1,410 million and $1.21, respectively, compared to net loss attributable to Teva and loss per share of $1,639 million and $1.45, in 2024. This change was mainly due to the changes in operating income and income taxes, as discussed above, partially offset by net loss attributable to non-controlling interests in 2024. Non-GAAP net income attributable to Teva and non-GAAP diluted earnings per share in 2025 were $3,411 million and $2.93, respectively, compared to $2,860 million and $2.49 in 2024. Adjusted EBITDA was $5,305 million in 2025, compared to $4,781 million in 2024. As of December 31, 2025 and 2024, the fully diluted share count for purposes of calculating our market capitalization was approximately 1,184 million and 1,174 million, respectively. Non-GAAP information: non-GAAP adjustments for non-GAAP net income attributable to Teva and non-GAAP diluted EPS in 2025 were $2,001 million and consisted of the following adjustments: Amortization of purchased intangible assets totaling $581 million, of which $541 million is included in cost of goods sold and the remaining $40 million in S&M expenses;Legal settlements and loss contingencies of $473 million;Impairment of long-lived assets of $1,029 million;Restructuring expenses of $225 million;Equity compensation expenses of $157 million;Contingent consideration expenses of $54 million;Loss on sale of business of $22 million;Accelerated depreciation of $21 million;Financial expenses of $69 million;Items attributable to non-controlling interests of $2 million;Other non-GAAP items of $186 million; andCorresponding tax effects and unusual tax items of $819 million. We believe that excluding such items facilitates investors’ understanding of our business including underlying trends, thereby improving the comparability of our business performance results between reporting periods. For a reconciliation of the U.S. GAAP results to the adjusted non-GAAP figures and for additional information, see the tables below and the information included under “Non-GAAP Financial Measures.” Investors should consider non-GAAP financial measures in addition to, and not as replacement for, or superior to, measures of financial performance prepared in accordance with GAAP. Cash flow generated from operating activities in 2025 was $1,649 million, compared to $1,247 million in 2024. The increase in 2025 resulted mainly from development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), partially offset by higher legal settlement payments. Net changes in working capital items were neutral. During 2025, we generated free cash flow of $2,396 million, which we define as comprising $1,649 million in cash flow generated from operating activities, $1,214 million in beneficial interest collected in exchange for securitized accounts receivable (under our EU securitization program) and $34 million proceeds from divestitures of businesses and other assets, partially offset by $501 million in cash used for capital investments. During 2024, we generated free cash flow of $2,068 million, which we define as comprising $1,247 million in cash flow generated from operating activities, $1,291 million in beneficial interest collected in exchange for securitized accounts receivables (under our EU securitization program) and $43 million in proceeds from divestitures of businesses and other assets, partially offset by $498 million in cash used for capital investments and $15 million in cash used for acquisition of businesses, net of cash acquired. The increase in 2025 resulted mainly from higher cash flow generated from operating activities. As of December 31, 2025, our debt was $16,807 million, compared to $17,783 million as of December 31, 2024. This decrease was mainly due to repayment at maturity of $1,812 million of our senior notes, partially offset by an increase of $803 million due to exchange rate fluctuations. The portion of total debt classified as short-term as of December 31, 2025 was 11%, compared to 10% as of December 31, 2024. Our average debt maturity was approximately 5.6 years as of December 31, 2025, compared to 5.5 years as of December 31, 2024. Fourth Quarter 2025 Consolidated Results Revenues in the fourth quarter of 2025 were $4,711 million, an increase of 11% in U.S. dollars or 9% in local currency terms, compared to the fourth quarter of 2024. This increase was mainly due to development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A) and from higher revenues from our key innovative products, primarily AUSTEDO, partially offset by lower proceeds from the sale of certain product rights and lower revenues from our International Markets segment due to the divestment of our business venture in Japan. Exchange rate movements during the fourth quarter of 2025, net of hedging effects, positively impacted revenues by $99 million and negatively impacted both operating income and non-GAAP operating income by $18 million, each as compared to the fourth quarter of 2024. Gross profit in the fourth quarter of 2025 was $2,656 million, an increase of 25% compared to $2,120 million in the fourth quarter of 2024. Gross profit margin was 56.4% in the fourth quarter of 2025, compared to 50.1% in the fourth quarter of 2024. Non-GAAP gross profit was $2,840 million in the fourth quarter of 2025, an increase of 22%, compared to $2,319 million in the fourth quarter of 2024. Non-GAAP gross profit margin was 60.3% in the fourth quarter of 2025, compared to 54.8% in the fourth quarter of 2024. The increase in both gross profit margin and non-GAAP gross profit margin was mainly due to the development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), and a favorable mix of products, primarily driven by higher revenues from AUSTEDO, partially offset by lower proceeds from the sale of certain product rights. Research and Development (R&D) expenses, net in the fourth quarter of 2025 were $267 million, an increase of 8% compared to $248 million in the fourth quarter of 2024. Our higher R&D expenses, net in the fourth quarter of 2025, were mainly due to an increase in our late-stage innovative pipeline in immunology, partially offset by a decline in our late-stage innovative pipeline in neuroscience, the non-recurrence of milestone payments related to certain biosimilar projects, as well as lower expenses related to generics projects. Selling and Marketing (S&M) expenses in the fourth quarter of 2025 were $753 million, an increase of 16% compared to the fourth quarter of 2024. This increase was mainly to support revenue growth in our innovative portfolio, primarily AUSTEDO, and due to a negative impact from exchange rate fluctuations. General and Administrative (G&A) expenses in the fourth quarter of 2025 were $367 million, an increase of 22% compared to the fourth quarter of 2024. This increase was mainly due to costs related to optimization activities of Teva’s global organization and operations in connection with Teva’s Transformation programs, as well as a negative impact from exchange rate fluctuations. Operating income in the fourth quarter of 2025 was $300 million, compared to an operating loss of $29 million in the fourth quarter of 2024. Operating income as a percentage of revenues was 6.4% in the fourth quarter of 2025, compared to an operating loss as a percentage of revenues of 0.7% in the fourth quarter of 2024. This increase was mainly due to higher gross profit, as well as goodwill impairment charges in the fourth quarter of 2024, partially offset by higher charges related to other assets impairment, restructuring and other items. Non-GAAP operating income in the fourth quarter of 2025 was $1,532 million representing a non-GAAP operating margin of 32.5%, compared to non-GAAP operating income of $1,168 million representing a non-GAAP operating margin of 27.6% in the fourth quarter of 2024. The increase in non-GAAP operating margin in the fourth quarter of 2025 was due to an increase in non-GAAP gross profit margin, as discussed above. Financial expenses, net in the fourth quarter of 2025 were $220 million, mainly comprised of net-interest expenses of $200 million. In the fourth quarter of 2024, financial expenses, net were $218 million, mainly comprised of net-interest expenses of $224 million. In the fourth quarter of 2025, we recognized a tax benefit of $389 million, on a pre-tax income of $80 million. In the fourth quarter of 2024, we recognized a tax expense of $29 million, on a pre-tax loss of $247 million. Our effective tax rate for the fourth quarter of 2025 was the result of a variety of factors, including the geographic mix and type of products sold during the year, different effective tax rates applicable to non‐Israeli subsidiaries that have tax rates different than Teva’s average tax rate, adjustments to valuation allowances on deferred tax assets, net deferred tax benefits from intellectual property related integration plans and adjustments to uncertain tax positions. Non-GAAP tax rate in the fourth quarter of 2025 was 15.5%, compared to 14.8% in the fourth quarter of 2024. Our non-GAAP tax rate in the fourth quarter of 2025 was the result of a variety of factors, including the geographic mix and type of products sold during the year, different effective tax rates applicable to non‐Israeli subsidiaries that have tax rates different than Teva’s average tax rate, adjustments to valuation allowances on deferred tax assets, net deferred tax benefits from intellectual property related integration plans and adjustments to uncertain tax positions. Net income attributable to Teva and diluted earnings per share in the fourth quarter of 2025 were $480 million and $0.41, respectively, compared to net loss attributable to Teva and diluted loss per share of $217 million and $0.19, respectively, in the fourth quarter of 2024. This change was mainly due to higher gross profit and tax benefits as discussed above. Non-GAAP net income attributable to Teva and non-GAAP diluted earnings per share in the fourth quarter of 2025 were $1,130 million and $0.96, respectively, compared to $816 million and $0.71, respectively, in the fourth quarter of 2024. Adjusted EBITDA was $1,637 million in the fourth quarter of 2025, an increase of 28%, compared to $1,282 million in the fourth quarter of 2024. Non-GAAP information: non-GAAP adjustments for non-GAAP net income attributable to Teva and non-GAAP diluted EPS in the fourth quarter of 2025 were $649 million and consisted of the following adjustments: Amortization of purchased intangible assets of $145 million, of which $135 million is included in cost of sales and the remaining $10 million in S&M expenses;Impairment of long-lived assets in amount of $773 million;Legal settlements and loss contingencies of $164 million;Contingent consideration expenses of $8 million;Equity compensation expenses of $51 million;Restructuring expenses of $29 million;Loss on sale of business of $4 million;Accelerated depreciation of $9 million;Financial expenses of $11 million;Other non-GAAP items of $49 million; andCorresponding tax effects and unusual tax items of $594 million. We believe that excluding such items facilitates investors’ understanding of our business including underlying performance trends, thereby improving the comparability of our business performance results between reporting periods. For a reconciliation of the U.S. GAAP results to the adjusted non-GAAP figures and for additional information, see the tables below and the information included under “Non-GAAP Financial Measures.” Investors should consider non-GAAP financial measures in addition to, and not as replacement for, or superior to, measures of financial performance prepared in accordance with GAAP. Cash flow generated from operating activities during the fourth quarter of 2025 was $1,158 million, compared to $575 million in the fourth quarter of 2024. The higher cash flow generated from operating activities in the fourth quarter of 2025 resulted mainly from development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), as well as improvements in our net working capital, specifically accounts payable. During the fourth quarter of 2025, we generated free cash flow of $1,298 million, which we define as comprising $1,158 million in cash flow generated from operating activities, $282 million in beneficial interest collected in exchange for securitized accounts receivables (under our EU securitization program), partially offset by $142 million in cash used for capital investment. During the fourth quarter of 2024, we generated free cash flow of $790 million, which we define as comprising $575 million in cash flow generated from operating activities, $340 million in beneficial interest collected in exchange for securitized accounts receivables (under our EU securitization program) and $4 million proceeds from divestitures of businesses and other assets, partially offset by $129 million in cash used for capital investment. This increase resulted mainly from higher cash flow generated from operating activities. Segment Results for the Fourth Quarter of 2025 United States Segment The following table presents revenues, expenses and profit for our United States segment for the three months ended December 31, 2025 and 2024: Three months ended December 31, 2025 2024 (U.S. $ in millions / % of Segment Revenues) Revenues $ 2,643 100% $ 1,975 100% Cost of sales 820 31.0% 877 44.4% Gross profit 1,823 69.0% 1,097 55.6% R&D expenses 166 6.3% 158 8.0% S&M expenses 341 12.9% 260 13.2% G&A expenses 135 5.1% 109 5.5% Other § § 1 § Segment profit* $ 1,181 44.7% $ 569 28.8% *Segment profit does not include amortization and certain other items.§ Represents an amount less than $0.5 million or 0.5%, as applicable. Revenues from our United States segment in the fourth quarter of 2025 were $2,643 million, an increase of $668 million, or 34%, compared to the fourth quarter of 2024. This increase was mainly due to the development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), and higher revenues from our key innovative products, primarily AUSTEDO. Revenues by Major Products and Activities The following table presents revenues for our United States segment by major products and activities for the three months ended December 31, 2025 and 2024: Three months endedDecember 31, PercentageChange 2025 2024 2025-2024 (U.S. $ in millions) Generic products (including biosimilars) $ 673 $ 674 § AJOVY 105 63 68% AUSTEDO 725 518 40% BENDEKA®and TREANDA® 35 41 (14%) COPAXONE® 77 63 22% UZEDY 55 43 28% Anda 366 402 (9%) Other* 608 171 255% Total $ 2,643 $ 1,975 34% § Represents an amount less than 0.5%.*Other revenues in the fourth quarter of 2025 were mainly comprised of development milestone payments of $500 million received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A). Other revenues in the fourth quarter of 2024 include the sale of certain product rights. Generic products (including biosimilars) revenues in our United States segment in the fourth quarter of 2025 were $673 million, flat compared to the fourth quarter of 2024. Among the most significant generic products we sold in the United States in the fourth quarter of 2025 were Truxima® (the biosimilar to Rituxan®), epinephrine injectable solution (the generic equivalent of EpiPen® and EpiPen Jr®) and Fidaxomicin tablets (the generic equivalent of Dificid®). In the fourth quarter of 2025, our total prescriptions were approximately 254 million (based on trailing twelve months), representing 6.5% of total U.S. generic prescriptions, compared to approximately 283 million (based on trailing twelve months), representing 7.4% of total U.S. generic prescriptions in the fourth quarter of 2024, all according to IQVIA data. AJOVY revenues in our United States segment in the fourth quarter of 2025 were $105 million, an increase of 68% compared to the fourth quarter of 2024, mainly due to growth in volume. In the fourth quarter of 2025, AJOVY’s exit market share in the United States in terms of total number of prescriptions was 33.3% out of subcutaneous injectable anti-CGRP class, compared to 29.6% in the fourth quarter of 2024. AUSTEDO revenues (which include AUSTEDO XR®) in our United States segment in the fourth quarter of 2025 were $725 million, an increase of 40%, compared to $518 million in the fourth quarter of 2024. This increase was mainly due to growth in volume and a reduction in sales allowances. AUSTEDO XR (deutetrabenazine) extended-release tablets was approved by the FDA on February 17, 2023 in three doses of 6, 12 and 24 mg, and became commercially available in the U.S. in May 2023. The FDA approved AUSTEDO XR as a one pill, once-daily treatment option in doses of 30, 36, 42, and 48 mg in May 2024 and in 18 mg dose in July 2024. AUSTEDO XR is a once-daily formulation indicated in adults for tardive dyskinesia and chorea associated with Huntington’s disease, which is additional to the currently marketed twice-daily AUSTEDO. AUSTEDO XR is protected by 11 Orange Book patents expiring between 2031 and 2041. During 2025, Teva and the Centers for Medicare and Medicaid Services (“CMS”) negotiated a maximum fair price for AUSTEDO and AUSTEDO XR, based on CMS’s list of prescription medicines selected for price-setting discussions, in which they were originally included. The agreement was announced by the CMS in November 2025. The revised prices set by the U.S. Government will become effective on January 1, 2027 and will apply to eligible Medicare patients. UZEDY (risperidone) extended-release injectable suspension revenues in our United States segment in the fourth quarter of 2025 were $55 million, an increase of 28% compared to the fourth quarter of 2024, mainly due to growth in volume. BENDEKA and TREANDA combined revenues in our United States segment in the fourth quarter of 2025 were $35 million, a decrease of 14% compared to the fourth quarter of 2024, mainly due to competition from alternative therapies, as well as from generic bendamustine products. COPAXONE revenues in our United States segment in the fourth quarter of 2025 were $77 million, an increase of 22% compared to the fourth quarter of 2024, mainly due to reduction in sales allowances, partially offset by lower volumes. Anda revenues from third-party products in our United States segment in the fourth quarter of 2025 were $366 million, a decrease of 9%, compared to $402 million in the fourth quarter of 2024. This decrease was mainly due to lower volumes. Anda, our distribution business in the United States, distributes generic and innovative medicines and OTC pharmaceutical products from Teva and various third-party manufacturers to independent retail pharmacies, pharmacy retail chains, hospitals and physician offices in the United States. For information on a change to our reporting segments commencing January 1, 2026, see below under “Post-quarter Developments.” United States Gross Profit Gross profit from our United States segment in the fourth quarter of 2025 was $1,823 million, an increase of 66%, compared to $1,097 million in the fourth quarter of 2024. Gross profit margin for our United States segment in the fourth quarter of 2025 increased to 69.0%, compared to 55.6% in the fourth quarter of 2024. This increase was mainly due to the development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), and a favorable mix of products primarily driven by higher revenues from AUSTEDO. United States Profit Profit from our United States segment consists of revenues less cost of sales, R&D expenses, S&M expenses, G&A expenses and other expenses (income) related to this segment. Segment profit does not include amortization and certain other items. Profit from our United States segment in the fourth quarter of 2025 was $1,181 million, an increase of 108% compared to $569 million in the fourth quarter of 2024. This increase was mainly due to higher gross profit, as discussed above. Europe Segment Our Europe segment includes the European Union, the United Kingdom and certain other European countries. The following table presents revenues, expenses and profit for our Europe segment for the three months ended December 31, 2025 and 2024: Three months ended December 31, 2025 2024 (U.S. $ in millions / % of Segment Revenues) Revenues $ 1,314 100% $ 1,353 100% Cost of sales 606 46.1% 561 41.4% Gross profit 708 53.9% 792 58.6% R&D expenses 65 5.0% 56 4.2% S&M expenses 250 19.0% 221 16.3% G&A expenses 84 6.4% 75 5.6% Other 1 § 2 § Segment profit* $ 308 23.4% $ 438 32.4% *Segment profit does not include amortization and certain other items.§ Represents an amount less than $0.5 million or 0.5%, as applicable. Revenues from our Europe segment in the fourth quarter of 2025 were $1,314 million, a decrease of 3%, or $39 million, compared to the fourth quarter of 2024. In local currency terms, revenues decreased by 10% compared to the fourth quarter of 2024, mainly due to lower proceeds from the sale of certain product rights, lower revenues from generic and OTC products and COPAXONE, partially offset by higher revenues from AJOVY. In the fourth quarter of 2025, revenues were positively impacted by exchange rate fluctuations of $90 million, net of hedging effects, compared to the fourth quarter of 2024. Revenues in the fourth quarter of 2025 included a negligible hedging impact. Revenues in the fourth quarter of 2024 included $20 million from a positive hedging impact, which is included in “Other” in the table below. Revenues by Major Products and Activities The following table presents revenues for our Europe segment by major products and activities for the three months ended December 31, 2025 and 2024: Three months endedDecember 31, PercentageChange 2025 2024 2025-2024 (U.S. $ in millions) Generic products (including OTC and biosimilars) $ 1,033 $ 979 5% AJOVY 76 58 30% COPAXONE 45 50 (9%) Respiratory products 65 61 6% Other* 96 205 (53%) Total $ 1,314 $ 1,353 (3%) *Other revenues in the fourth quarter of 2025 and 2024 include the sale of certain product rights. Generic products revenues (including OTC and biosimilar products) in our Europe segment in the fourth quarter of 2025, were $1,033 million, an increase of 5% compared to the fourth quarter of 2024. In local currency terms, revenues decreased by 4%, mainly due to lower volumes and price reductions as a result of market dynamics, and lower sales of seasonal OTC products, partially offset by higher revenues from recently launched products. AJOVY revenues in our Europe segment in the fourth quarter of 2025 increased by 30% to $76 million, compared to $58 million in the fourth quarter of 2024. In local currency terms revenues increased by 19% due to growth in volume. COPAXONE revenues in our Europe segment in the fourth quarter of 2025 were $45 million, a decrease of 9% compared to the fourth quarter of 2024. In local currency terms revenues decreased by 17%, due to price reductions and lower volumes resulting from the availability of alternative therapies. Respiratory products revenues in our Europe segment in the fourth quarter of 2025 were $65 million, an increase of 6% compared to the fourth quarter of 2024. In local currency terms, revenues decreased by 2%, mainly due to net price reductions and lower volumes. Europe Gross Profit Gross profit from our Europe segment in the fourth quarter of 2025 was $708 million, a decrease of 11% compared to $792 million in the fourth quarter of 2024. Gross profit margin for our Europe segment in the fourth quarter of 2025 decreased to 53.9%, compared to 58.6% in the fourth quarter of 2024. This decrease was mainly due to lower proceeds from the sale of certain product rights, a negative impact from hedging activities and an unfavorable change in the mix of products. Europe Profit Profit from our Europe segment consists of revenues less cost of sales, R&D expenses, S&M expenses, G&A expenses and other expenses (income) related to this segment. Segment profit does not include amortization and certain other items. Profit from our Europe segment in the fourth quarter of 2025 was $308 million, a decrease of 30%, compared to $438 million in the fourth quarter of 2024. This decrease was mainly due to lower gross profit and higher operating expenses. International Markets Segment Our International Markets segment includes all countries in which we operate other than the United States and the countries included in our Europe segment. The International Markets segment covers a substantial portion of the global pharmaceutical industry, including more than 35 countries. The countries in our International Markets segment include highly regulated, mainly generic markets, such as Canada and Israel, and branded generics-oriented markets, such as Russia and certain Latin America markets. On March 31, 2025, we divested our Teva-Takeda business venture in Japan, which included generic products and legacy products. Since the establishment of the business venture and until the completion of its sale, Teva held 51% of the outstanding common stock of the business venture. On March 31, 2025, we deconsolidated the business venture from our financial statements. The following table presents revenues, expenses and profit for our International Markets segment for the three months ended December 31, 2025 and 2024: Three months ended December 31, 2025 2024 (U.S. $ in millions / % of Segment Revenues) Revenues $ 528 100% $ 661 100% Cost of sales 281 53.1% 315 47.7% Gross profit 247 46.9% 346 52.3% R&D expenses 27 5.2% 27 4.1% S&M expenses 121 23.0% 137 20.7% G&A expenses 40 7.6% 42 6.3% Other (11) § (1) § Segment profit* $ 70 13.3% $ 141 21.4% *Segment profit does not include amortization and certain other items.§ Represents an amount less than $0.5 million or 0.5%, as applicable. Revenues from our International Markets segment in the fourth quarter of 2025 were $528 million, a decrease of 20% in both U.S. dollars and local currency terms, compared to the fourth quarter of 2024. This decrease was mainly due to the divestment of our business venture in Japan, lower proceeds from the sale of certain product rights, as well as a negative hedging impact, partially offset by higher revenues from generic products in other markets and AJOVY. In the fourth quarter of 2025, revenues were positively impacted by exchange rate fluctuations of $2 million, net of hedging effects, compared to the fourth quarter of 2024. Revenues in the fourth quarter of 2025 included $14 million from a negative hedging impact, compared to a positive hedging impact of $13 million in the fourth quarter of 2024, which are included in “Other” in the table below. The following table presents revenues for our International Markets segment by major products and activities for the three months ended December 31, 2025 and 2024: Three months endedDecember 31, PercentageChange 2025 2024 2025-2024 (U.S. $ in millions) Generic products (including OTC and biosimilars) $ 422 $ 497 (15%) AJOVY 30 22 40% AUSTEDO 9 7 29% COPAXONE 6 9 (31%) Other* 60 126 (52%) Total $ 528 $ 661 (20%) *Other revenues in the fourth quarter of 2025 and 2024 include the sale of certain product rights. Generic products revenues (including OTC and biosimilar products) in our International Markets segment were $422 million in the fourth quarter of 2025, a decrease of 15% in U.S. dollars or 20% in local currency terms, compared to the fourth quarter of 2024, mainly due to the divestment of our business venture in Japan, partially offset by higher revenues in other markets. AJOVY revenues in our International Markets segment in the fourth quarter of 2025 were $30 million, compared to $22 million in the fourth quarter of 2024. In local currency terms, revenues increased by 35%, mainly due to growth in volume. AUSTEDO revenues in our International Markets segment in the fourth quarter of 2025 were $9 million compared to $7 million in the fourth quarter of 2024. In local currency terms, revenues increased by 21%. In February 2024, we announced a strategic partnership for the marketing and distribution of AUSTEDO in China. In April 2025, AUSTEDO received marketing authorization in South Korea. We continue to evaluate additional submissions in various other markets. COPAXONE revenues in our International Markets segment in the fourth quarter of 2025 were $6 million compared to $9 million in the fourth quarter of 2024. International Markets Gross Profit Gross profit from our International Markets segment in the fourth quarter of 2025 was $247 million, a decrease of 28% compared to $346 million in the fourth quarter of 2024. Gross profit margin for our International Markets segment in the fourth quarter of 2025 decreased to 46.9%, compared to 52.3% in the fourth quarter of 2024. This decrease was mainly due to lower proceeds from the sale of certain product rights and a negative hedging impact, partially offset by price increases due to inflationary pressures in certain markets and a favorable mix of products. International Markets Profit Profit from our International Markets segment consists of revenues less cost of sales, R&D expenses, S&M expenses, G&A expenses and other expenses (income) related to this segment. Segment profit does not include amortization and certain other items. Profit from our International Markets segment in the fourth quarter of 2025 was $70 million, a decrease of 50%, compared to $141 million in the fourth quarter of 2024. This decrease was mainly due to lower proceeds from the sale of certain product rights, a negative hedging impact, as well as the divestment of our business venture in Japan. Other Activities We have other sources of revenues, primarily the sale of APIs to third parties, certain contract manufacturing services and an out-licensing platform offering a portfolio of products to other pharmaceutical companies through our affiliate Medis. Our other activities are not included in our United States, Europe or International Markets segments described above. For information on a change to our reporting segments commencing January 1, 2026, see below under “Post Quarter Developments.” Revenues from other activities in the fourth quarter of 2025 were $226 million, a decrease of 6% in U.S. dollars, or 9% in local currency terms, compared to the fourth quarter of 2024, mainly due to a decrease in revenues from contract manufacturing services. API sales to third parties in the fourth quarter of 2025 were $136 million, a decrease of 4% in both U.S. dollars and local currency terms, compared to the fourth quarter of 2024. Post Quarter Developments To align with Teva's Pivot to Growth strategy, commencing January 1, 2026, Anda will no longer be reported under Teva's United States segment. This shift will allow the United States segment to continue to manage its entire product portfolio in the region, while strengthening focus on its biopharmaceutical business, growth engines and innovation. As a result, from that date, Anda will be reported as part of the Company’s Other Activities. In January 2026, we announced a funding agreement to accelerate the development of anti-IL-15 (TEV-‘408) for vitiligo with Royalty Pharma; in addition, Teva and Abingworth signed an amendment to the development funding agreement to increase the total development funding by an additional $50 million for DARI (ICS-SABA). 2026 Financial Outlook $ billions, except diluted EPS or as noted 2026 Outlook Revenues 16.4 - 16.8 AUSTEDO ($m) 2,400 - 2,550 AJOVY ($m) 750 - 790 UZEDY ($m) 250 - 280 Operating Income* 4.55-4.8 Adjusted EBITDA* 5.0-5.3 Finance Expenses* ($m) ~800 Tax Rate* 16% - 19% Diluted EPS* ($) 2.57 - 2.77 Free Cash Flow* 2.0 - 2.4 CAPEX 0.5 Foreign Exchange Volatile swings in FX can negativelyimpact revenue and income 1,177M shares *Certain items above are non-GAAP financial measures. For more information, see “Non-GAAP Financial Measures” below. Free Cash Flow includes cash flow generated from operating activities net of capital expenditures and deferred purchase price cash component collected for securitized trade receivables. Annual Report on Form 10-K Teva's Annual Report on Form 10-K for the year ended December 31, 2025, which will be filed with the SEC, will be available on Teva’s website: http://ir.tevapharm.com, as well as on the SEC’s website: http://www.sec.gov. Conference Call Teva will host a conference call and live webcast along with a slide presentation on Wednesday, January 28, 2026 at 8:00 a.m. ET to discuss its fourth quarter of 2025 and annual 2025 financial results and overall business environment. A question & answer session will follow. In order to participate, please register in advance here to obtain a local or toll-free phone number and your personal pin.A live webcast of the call will be available on Teva's website at: https://ir.tevapharm.com/Events-and-Presentations. About Teva Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is transforming into a leading innovative biopharmaceutical company, enabled by a world-class generics business. For over 120 years, Teva’s commitment to bettering health has never wavered. From innovating in the fields of neuroscience and immunology to providing complex generic medicines, biosimilars and pharmacy brands worldwide, Teva is dedicated to addressing patients’ needs, now and in the future. At Teva, We Are All In For Better Health. To learn more about how, visit www.tevapharm.com. Some amounts in this press release may not add up due to rounding. All percentages have been calculated using unrounded amounts. Non-GAAP Financial Measures This press release contains certain financial information that differs from what is reported under accounting principles generally accepted in the United States ("GAAP"). These non-GAAP financial measures, including, but not limited to, non-GAAP operating income, non-GAAP operating margin, non-GAAP gross profit, non-GAAP gross profit margin, Adjusted EBITDA, free cash flow, non-GAAP tax rate, non-GAAP net income (loss) attributable to Teva and non-GAAP diluted EPS, are presented in order to facilitate investors' understanding of our business. We utilize certain non-GAAP financial measures to evaluate performance in conjunction with other performance metrics. The following are examples of how we utilize the non-GAAP measures: our management and board of directors use the non-GAAP measures to evaluate our operational performance and, to compare our results against work plans and budgets, and ultimately to evaluate the performance of management; our annual budgets are prepared on a non-GAAP basis; and senior management’s annual compensation is derived, in part, using these non-GAAP measures. See the attached tables for a reconciliation of the GAAP results to the adjusted non-GAAP measures. Investors should consider non-GAAP financial measures in addition to, and not as replacements for, or superior to, measures of financial performance prepared in accordance with GAAP. We are not providing the most comparable forward-looking GAAP measures for non-GAAP metrics included in our financial outlook or a quantitative reconciliation of forward-looking non-GAAP financial measures to the most directly comparable GAAP measures because we are unable to predict with reasonable certainty the ultimate outcome of certain significant items including, but not limited to, the amortization of purchased intangible assets, legal settlements and loss contingencies, impairment of long-lived assets and goodwill impairment, without unreasonable effort. These items are uncertain, depend on various factors, and could be material to our results computed in accordance with GAAP. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. These forward-looking statements include statements concerning our plans, strategies, objectives, future performance and financial and operating targets, and any other information that is not historical information. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe,” "outlook" and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully compete in the marketplace, including: that we are substantially dependent on our generic products; concentration of our customer base and commercial alliances among our customers; competition faced by our generic medicines from other pharmaceutical companies and changes in regulatory policy that may result in costs and delays; delays in launches of new generic products; our ability to develop and commercialize additional pharmaceutical products in a timely manner; intense competition for our innovative medicines; our ability to achieve expected results from investments in our product pipeline; our ability to successfully execute our Pivot to Growth strategy, including to expand our innovative and biosimilar medicines pipeline and profitably commercialize our innovative medicines and biosimilar portfolio, whether organically or through business development, to sustain and focus our portfolio of generic medicines, and to execute on our organizational transformation and to achieve expected cost savings; and the effectiveness of our patents and other measures to protect our intellectual property rights;our significant indebtedness, which may limit our ability to incur additional indebtedness, engage in additional transactions or make new investments; and our potential need to raise additional funds in the future, which may not be available on acceptable terms or at all;our business and operations in general, including: the impact of global economic conditions and other macroeconomic developments and the governmental and societal responses thereto, and our exposure to changes in international trade policies, including the imposition of tariffs in the jurisdictions in which we operate, and any effects of such developments on sales of our products and the pricing and availability of our raw materials; effectiveness of our optimization efforts; significant disruptions of information technology systems, including cybersecurity attacks, as well as risks and uncertainties related to the adoption of artificial intelligence technologies, and breaches of our data security; interruptions in our supply chain or problems with internal or third party manufacturing; challenges associated with conducting business globally, including political or economic instability, prolonged government shutdowns, widespread outbreaks of major diseases and major hostilities or acts of terrorism, such as the ongoing conflicts between Russia and Ukraine and in the Middle East; our ability to attract, hire, integrate and retain highly skilled personnel; our ability to successfully bid for suitable acquisition targets or licensing opportunities, or to consummate and integrate acquisitions; and our prospects and opportunities for growth if we sell assets or business units and close or divest plants and facilities, as well as our ability to successfully and cost-effectively consummate such sales and divestitures, including our planned divestiture of our API business;compliance, regulatory and litigation matters, including: failure to comply with complex legal and regulatory requirements, the effects of regulatory uncertainty and changes and the results of increased regulatory oversight, including expenditures required to ensure compliance with research, production and quality control regulations and remedial actions taken to address product issues, such as delayed product launches, product recalls, and facility shutdowns; the effects of governmental, regulatory and civil proceedings and litigation which we are, or in the future become, party to; the effects of reforms in healthcare regulation and related reductions in pharmaceutical pricing, reimbursement and coverage, including as a result of the One Big Beautiful Bill signed into law in the U.S. in July 2025 (“OBBBA”), which will likely reduce the number of insured in Medicaid and Health Insurance Exchange markets, which may alter utilization patterns and shift negotiating leverage among payors, U.S. Executive Orders issued in April and May 2025 intended to reduce the prices paid by Americans for prescription medicines, including Most-Favored-Nation pricing; legal and regulatory actions in connection with public concern over the abuse of opioid medications; our ability to timely make payments required under our nationwide opioids settlement agreement and provide our generic version of Narcan® (naloxone hydrochloride nasal spray) in the amounts and at the times required under the terms of such agreement; scrutiny from competition and pricing authorities around the world, including our ability to comply with and operate under our deferred prosecution agreement (“DPA”) with the U.S. Department of Justice (“DOJ”); potential liability for intellectual property right infringement; significant product liability claims; claims brought by regulatory agencies; failure to comply with complex Medicare, Medicaid and other governmental programs’ reporting and payment obligations; compliance with sanctions and trade control laws; environmental risks and changes in governmental, investor and societal responses to climate change and sustainability related issues; other financial and economic risks, including: our exposure to currency fluctuations and restrictions as well as credit risks; impairments of our long-lived assets; potential significant increases in tax liabilities; the effect on our overall effective tax rate of the termination or expiration of governmental programs or tax benefits, or of a change in our business; and the impact of any failure to maintain effective internal control over our financial reporting; and other factors discussed in this press release, in our Annual Report on Form 10-K for the year ended December 31, 2024, including in the section captioned "Risk Factors” and in other periodic reports we subsequently file with the SEC available on the SEC’s website: http://www.sec.gov. Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward‐looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements. Consolidated Statements of Income(U.S. dollars in millions, except share and per share data)Unaudited Three months ended Year ended December 31, December 31, 2025 2024 2025 2024Net revenues 4,711 4,229 17,258 16,544Cost of sales 2,056 2,109 8,320 8,481Gross profit 2,656 2,120 8,938 8,064Research and development expenses 267 248 1,013 998Selling and marketing expenses 753 650 2,686 2,541General and administrative expenses 367 302 1,287 1,161Intangible assets impairments 32 81 259 251Goodwill impairment - 280 - 1,280Other asset impairments, restructuring and other items.................................................... 778 457 1,050 1,388Legal settlements and loss contingencies........................................................................... 155 123 467 761Other (income) loss ............................................................................................................ 3 8 18 (14)Operating income (loss) 300 (29) 2,157 (303)Financial expenses, net 220 218 934 981Income (loss) before income taxes 80 (247) 1,223 (1,284)Income taxes (benefit)..................................................................................... (389) 29 (180) 676Share in (profits) losses of associated companies, net (11) (1) (15) (1)Net income (loss) 481 (275) 1,418 (1,959)Net income (loss) attributable to non-controlling interests § (58) 7 (320)Net income (loss) attributable to Teva 480 (217) 1,410 (1,639) Earnings (loss) per share attributable to Teva:Basic ($)0.42 (0.19) 1.23 (1.45) Diluted ($)0.41 (0.19) 1.21 (1.45)Weighted average number of shares (in millions):Basic1,149 1,133 1,145 1,131 Diluted1,173 1,133 1,163 1,131 Non-GAAP net income attributable to Teva for diluted earnings per share:* 1,130 816 3,411 2,860 Non-GAAP earnings per share attributable to Teva:*Diluted ($)0.96 0.71 2.93 2.49 Non-GAAP average number of shares (in millions):Diluted1,173 1,157 1,163 1,150 Amounts may not add up due to rounding. § Represents an amount less than $0.5 million. * See reconciliation attached. Condensed Consolidated Balance Sheets (U.S. dollars in millions)Audited December 31, December 31, 2025 2024 ASSETS Current assets: Cash and cash equivalents 3,556 3,300Accounts receivables, net of allowance for credit losses of $81 million and $78 million as of December 31, 2025 and December 31, 2024 3,709 3,059Inventories 3,179 3,007Prepaid expenses 1,122 1,006Other current assets 539 409Assets held for sale 1,842 1,771Total current assets 13,946 12,552Deferred income taxes 2,191 1,799Other non-current assets 405 462Property, plant and equipment, net 4,080 4,581Operating lease right-of-use assets 345 367Identifiable intangible assets, net 3,781 4,418Goodwill 16,000 15,147Total assets 40,748 39,326 LIABILITIES & EQUITY Current liabilities: Short-term debt 1,820 1,781Sales reserves and allowances 4,143 3,678Trade payables 2,531 2,203Employee-related obligations 739 624Accrued expenses 2,687 2,792Other current liabilities 1,182 1,020Liabilities held for sale 354 698Total current liabilities 13,456 12,796 Long-term liabilities: Deferred income taxes 296 483Other taxes and long-term liabilities 3,808 4,028Senior notes and loans 14,986 16,002Operating lease liabilities 288 296Total long-term liabilities 19,379 20,809Redeemable non-controlling interests - 340 Equity: Teva shareholders’ equity: 7,910 5,373Non-controlling interests....................................................... 4 7Total equity 7,914 5,380Total liabilities and equity 40,748 39,326 TEVA PHARMACEUTICAL INDUSTRIES LIMITEDCONSOLIDATED STATEMENTS OF CASH FLOWS(U.S. dollars in millions)Unaudited Year ended Three months ended December 31, December 31, 2025 2024 2025 2024 Operating activities: (Audited) (Audited) Unaudited UnauditedNet income (loss)........................................................................................... 1,418 —(1,959) $480 $(275)Adjustments to reconcile net income (loss) to net cash provided by operations: Impairment of goodwil - 1,280 - 280Impairment of long-lived assets and assets held for sale........... 1,028 1,275 773 517Depreciation and amortization....................................................................... 1,002 1,059 260 269Net change in operating assets and liabilities............................................... (1,366) (435) 181 (246)Deferred income taxes — net and uncertain tax positions......................... (671) (634) (595) 32Stock-based compensation............................................................................. 157 123 51 34Net loss (gain) from sale of business and long-lived assets - (22) - -Other items,net* ..................................................................................................... 81 560 8 (37)Net cash provided by (used in) operating activities.......................................................................................1,649 1,247 1,158 575 Investing activities: Beneficial interest collected in exchange for securitized trade receivables 1,214 1,291 282 340Purchases of property, plant and equipment and intangible assets............. (501) (498) (142) (129)Proceeds from sale of business and long lived assets................................. 34 43 - 4Purchases of investments and other assets................................................... (57) (71) (17) (15)Proceeds from sale of investments............................................................... 42 40 41 -Acquisitions of businesses, net of cash acquired ........................................ - (15) - -Other investing activities................................................................................ 5 2 1 2Net cash provided by (used in) investing activities............................... 737 792 165 202 Financing activities: Repayment of senior notes and loans and other long term liabilities........ (4,112) (1,641) - (685)Proceeds from senior notes, net of issuance costs..................................... 2,298 - - -Purchase of shares from redeemable and non-redeemable non-controlling interests (38) (64) - -Dividends paid to redeemable and non-redeemable non-controlling interests (340) (78) - -Other financing activities............................................................................... 41 (8) 40 10Net cash provided by (used in) financing activities.............................. (2,151) (1,791) 40 675Translation adjustment on cash, cash equivalents and restricted cash 21 (174) (10) (121)Net change in cash, cash equivalents and restricted cash$256 $74 $1,353 $(19)Balance of cash, cash equivalents and restricted cash at beginning of year 3,300 3,227 2,203 3,319Balance of cash, cash equivalents and restricted cash at end of year 3,556 3,300 3,556 3,300 Reconciliation of cash, cash equivalents and restricted cash reported in the consolidated balance sheets: Cash and cash equivalents 3,556 3,300 3,556 3,300Restricted cash included in other current assets - - - -Total cash, cash equivalents and restricted cash shown in the statements of cash flows 3,556 3,300 3,556 3,300 *"Other items, net" in the year ended December 31, 2024 includes mainly amounts related to an agreement with the Israeli Tax Authorities. Reconciliation of net income (loss) attributable to Tevato Non-GAAP net income (loss) attributable to Teva Unaudited Three months ended Year ended December 31, December 31,($ in millions except per share amounts) 20252024 2025 2024Net income (Loss) attributable to Teva($)480(217) ($)1,410 (1,639)Increase (decrease) for excluded items: Amortization of purchased intangible assets 145144 581 588 Legal settlements and loss contingencies(1) 164123 473 761 Goodwill impairment(2) -280 - 1,280 Impairment of long-lived assets(3) 773517 1,029 1,275 Restructuring costs(4) 2922 225 74 Equity compensation 5134 157 123 Contingent consideration(5) 8(2) 54 303 Loss (Gain) on sale of business 46 22 (15) Accelerated depreciation 95 21 13 Financial expenses 1113 69 49 Items attributable to non-controlling interests(3) -(63) 2 (339) Other non-GAAP items(6) 4967 186 229 Corresponding tax effects and unusual tax items(7) (594)(114) (819) 157Non-GAAP net income attributable to Teva($)1,130816 ($)3,411 2,860Non-GAAP tax rate(8) 15.5%14.8% 15.8% 15.3%GAAP diluted earnings (loss) per share attributable to Teva($)0.41(0.19) ($)1.21 (1.45)EPS difference(9) 0.550.90 1.72 3.94Non-GAAP diluted EPS attributable to Teva(9)($)0.960.71 ($)2.93 2.49Non-GAAP average number of shares (in millions)(9) 1,1731,157 1,163 1,150 (1)For the forth quarter of 2025, adjustments of legal settlements and loss contingencies mainly consisted of $81 million related to the provision for the opioid cases (mainly the effect of the passage of time on the net present value of the discounted payments), an update of $56 million related to the provision recorded for the carvedilol patent litigation. Adjustments for legal settlements and loss contingencies in 2025 were mainly related to an update to the estimated settlement provision of $220 million for the opioid cases (mainly the effect of the passage of time on the net present value of the discounted payments), an update of $56 million related to the provision recorded for the carvedilol patent litigation, an update of $55 million related to the estimated provision recorded for the claims brought by attorneys general representing states and territories throughout the United States in the generic drug antitrust litigation, as well as a provision of $35 million recorded for the antitrust litigation related to QVAR. Adjustments for legal settlements and loss contingencies in 2024 were mainly related to legal expenses of $357 million recorded in connection with a decision by the European Commission in its antitrust investigation into COPAXONE, and an update to the estimated settlement provision of $278 million for the opioid cases (mainly the effect of the passage of time on the net present value of the discounted payments and the settlement agreement with the city of Baltimore).(2)During the fourth quarter of 2024 a goodwill impairment charge of $280 million was recorded related to our API reporting unit. During the year ended December 31, 2024 goodwill impairment charges of $1,280 million were recorded related to our API reporting unit.(3)Adjustments for impairment of long-lived assets in the fourth quarter of 2025 primarily consisted of $726 million impairment charge in connection with manufacturing facility in Europe. Adjustments for impairment of long-lived assets and items attributable to non-controlling interests, in the fourth quarter of 2024 primarily consisted of $129 million and $63 million, respectively, related to the classification of the business venture in Japan as held for sale. In addition, in the fourth quarter of 2024 we recognized an impairment of $275 million related to the classification of our API business (including its R&D, manufacturing and commercial activities) as held for sale. Adjustments for impairment of long-lived assets in 2025 were mainly related to a $726 million impairment charge in connection with manufacturing facility in Europe. Adjustments for impairment of long-lived assets and items attributable to non-controlling interests in 2024 primarily consisted of $715 million and $342 million, respectively, related to the classification of our business venture in Japan as held for sale. In addition, in 2024 we recognized an impairment of $275 million related to the classification of our API business (including its R&D, manufacturing and commercial activities) as held for sale.(4)In 2025, Teva recorded $225 million of restructuring expenses primarily related to optimization activities in connection with Teva's Transformation programs related to Teva’s global organization and operations, mainly through headcount reduction.(5)Adjustments in 2024 primarily related to a change in the estimated future royalty payments to Allergan in connection with lenalidomide capsules (the generic version of Revlimid®) of $270 million.(6)Other non-GAAP items include other exceptional items that we believe are sufficiently large that their exclusion is important to facilitate an understanding of trends in our financial results, primarily related to the rationalization of our plants, certain inventory write-offs, material litigation fees and other unusual events.(7)Adjustments for corresponding tax effects and unusual tax items in the fourth quarter and year ended december 2025 include an income tax item in an amount of $246 million related to a valuation allowance release in the U.S. Adjustments for corresponding tax effects and unusual tax items in 2024 include a tax item in an amount of $495 million related to the settlement agreement with the ITA to settle certain litigation with respect to taxes payable for the Company’s taxable years 2008 through 2020.(8)Non-GAAP tax rate is tax expenses (benefit) excluding the impact of non-GAAP tax adjustments presented above as a percentage of income (loss) before income taxes excluding the impact of non-GAAP adjustments presented above.(9)EPS difference and diluted non-GAAP EPS are calculated by dividing our non-GAAP net income attributable to Teva by our non-GAAP diluted weighted average number of shares. Reconciliation of gross profit (loss) to Non-GAAP gross profit (loss) Unaudited Three months ended Year ended December 31, December 31,($ in millions) 20252024 20252024GAAP gross profit($)2,6562,120 ($)8,9388,064GAAP gross profit margin 56.4%50.1% 51.8%48.7%Increase (decrease) for excluded items:(1) Amortization of purchased intangible assets 135135 541543 Costs related to regulatory actions taken in facilities 53 68 Equity compensation 75 2423 Accelerated Depreciation 95 2013 Other non-GAAP items 2851 117164Non-GAAP gross profit($)2,8402,319 ($)9,6478,814Non-GAAP gross profit margin(2) 60.3%54.8% 55.9%53.3% (1)For further explanations, refer to the footnotes under the "Reconciliation of net income (loss) attributable to Teva to Non-GAAP net income (loss) attributable to Teva" table.(2)Non-GAAP gross profit margin is non-GAAP gross profit as a percentage of revenue. Reconciliation of net income (loss) to adjusted EBITDA Unaudited Three months ended Year ended, December 31, December 31,($ in millions) 20252024 20252024Net income (loss)$481(275) $1,418(1,959)Increase (decrease) for excluded items:(1) Financial expenses 220218 934981 Income taxes (389)29 (180)676 Share in profits (losses) of associated companies –net (11)(1) (15)(1) Depreciation 114119 421465 Amortization 145144 581588EBITDA 560235 3,159750 Legal settlements and loss contingencies 164123 473761 Goodwill impairment -280 -1,280 Impairment of long lived assets 773517 1,0291,275 Restructuring costs 2922 22574 Equity compensation 5134 157123 Contingent consideration 8(2) 54303 Loss (Gain) on sale of Business -6 -(15) Other non-GAAP items 5367 208229Adjusted EBITDA$1,6371,282 $5,3054,781 (1) For further explanations, refer to the footnotes under the "Reconciliation of net income (loss) attributable to Teva to Non-GAAP net income (loss) attributable to Teva" table. Reconciliation of operating income (loss) to Non-GAAP operating income (loss)Unaudited Three months ended Year ended, December 31, December 31,($ in millions) 20252024 20252024Operating income (loss)($)300(29) ($)2,157(303)Operating margin 6.4%(0.7%) 12.5%(1.8%)Increase (decrease) for excluded items:(1) Amortization of purchased intangible assets 145144 581588 Legal settlements and loss contingencies 164123 473761 Goodwill impairment -280 -1,280 Impairment of long-lived assets 773517 1,0291,275 Restructuring costs 2922 22574 Equity compensation 5134 157123 Contingent consideration 8(2) 54303 Loss (gain) on sale of business 46 22(15) Accelerated depreciation 95 2113 Other non-GAAP items 4967 186229Non-GAAP operating income (loss)($)1,5321,168 ($)4,9054,329Non-GAAP operating margin(2)($)32.5%27.6% ($)28.4%26.2% (1)For further explanations, refer to the footnotes under the "Reconciliation of net income (loss) attributable to Teva to Non-GAAP net income (loss) attributable to Teva" table.(2)Non-GAAP operating margin is Non-GAAP operating income as a percentage of revenues. Segment InformationUnaudited United States Europe International Markets Three months ended December 31, Three months ended December 31, Three months ended December 31, 2025 2024 2025 2024 2025 2024 (U.S. $ in millions) (U.S. $ in millions) (U.S. $ in millions) Revenues$2,643 $1,975 $1,314 $1,353 $528 $661Cost of sales 820 877 606 561 281 315Gross profit 1,823 1,097 708 792 247 346R&D expenses 166 158 65 56 27 27S&M expenses 341 260 250 221 121 137G&A expenses 135 109 84 75 40 42Other § 1 1 2 (11) (1)Segment profit*$1,181 $569 $308 $438 $70 $141 * Segment profit does not include amortization and certain other items. § Represents an amount less than $0.5 million. Segment InformationUnaudited United States Europe International Markets Year ended December 31, Year ended December 31, Year ended December 31, 2025 2024 2025 2024 2025 2024 (U.S. $ in millions) (U.S. $ in millions) (U.S. $ in millions) Revenues$9,186 $8,034 $5,040 $5,103 $2,162 $2,463Cost of sales 3,568 3,646 2,293 2,197 1,116 1,229Gross profit 5,618 4,388 2,747 2,905 1,046 1,235R&D expenses 633 633 247 229 103 112S&M expenses 1,172 1,049 902 826 475 534G&A expenses 458 410 295 272 147 150Other income § § 1 3 (14) (2)Segment profit$3,356 $2,296 $1,303 $1,575 $336 $440 * Segment profit does not include amortization and certain other items. § Represents an amount less than $0.5 million. Reconciliation of our segment profitto consolidated income (loss) before income taxesUnaudited Three months ended December 31, 2025 2024 (U.S.$ in millions) United States profit $1,181 $569Europe profit 308 438International Markets profit 70 141Total reportable segment profit 1,559 1,148Profit (loss) of other activities (27) 19Amounts not allocated to segments: Amortization 145 144Other asset impairments, restructuring and other items 778 458Goodwill impairment - 280Intangible asset impairments 32 81Legal settlements and loss contingencies 164 123Other unallocated amounts 112 110Consolidated operating income (loss) 300 (29)Financial expenses - net 220 218Consolidated income (loss) before income taxes $80 $(247) Reconciliation of our segment profitto consolidated income (loss) before income taxesUnaudited Year ended December 31, 2025 2024 (U.S.$ in millions) United States profit $3,356 $2,296Europe profit 1,303 1,575International Markets profit 336 440Total reportable segment profit 4,995 4,311Profit (loss) of other activities (90) 18Amounts not allocated to segments: Amortization 581 588Other asset impairments, restructuring and other items 1,050 1,388Goodwill impairment - 1,280Intangible asset impairments 259 251Legal settlements and loss contingencies 473 761Other unallocated amounts 384 364Consolidated operating income (loss) 2,157 (303)Financial expenses - net 934 981Consolidated income (loss) before income taxes $1,223 $(1,284) Segment revenues by major products and activitiesUnaudited Three months ended December 31, Percentage Change 2025 2024 2024-2025 (U.S.$ in millions) United States segment Generic products (including biosimilars)$673 $674 §AJOVY 105 63 68%AUSTEDO 725 518 40%BENDEKA/TREANDA 35 41 (14%)COPAXONE 77 63 22%UZEDY 55 43 28%Anda 366 402 (9%)Other* 608 171 255%Total 2,643 1,975 34% *Other revenues in the fourth quarter of 2025 were mainly comprised of development milestone payments of $500 million received in the fourth quarter of 2025, in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A). Other revenues in the fourth quarter of 2024 include the sale of certain product rights. Three months ended December 31, Percentage Change 2025 2024 2024-2025 (U.S.$ in millions) Europe segment Generic products (including biosimilars)$1,033 $979 5%AJOVY 76 58 30%COPAXONE 45 50 (9%)Respiratory products 65 61 6%Other* 96 205 (53%)Total 1,314 1,353 (3%) *Other revenues in the fourth quarter of 2025 and 2024 include the sale of certain product rights. Three months ended December 31, Percentage Change 2025 2024 2024-2025 (U.S.$ in millions) International Markets segment Generic products (including biosimilars)$422 $497 (15%)AJOVY 30 22 40%AUSTEDO 9 7 29%COPAXONE 6 9 (31%)Other* 60 126 (52%)Total 528 661 (20%) *Other revenues in the fourth quarter of 2025 and 2024 include the sale of certain product rights. Segment revenues by major products and activitiesAudited Year ended December 31, Percentage Change 2025 2024 2025-2024 (U.S.$ in millions) United States segment Generic products (including biosimilars) $3,657 $3,599 2%AJOVY 295 207 42%AUSTEDO 2,217 1,642 35%BENDEKA / TREANDA 147 168 (13%)COPAXONE 255 242 6%UZEDY 191 117 63%Anda 1,496 1,536 (3%)Other* 929 523 78%Total 9,186 8,034 14% * Other revenues in 2025 were mainly comprised of development milestone payments of $500 million received in the fourth quarter of 2025, in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A) (see note 2 to our consolidated financial statements). Other revenues in 2024 include the sale of certain product rights. Year ended December 31, Percentage Change 2025 2024 2025-2024 (U.S.$ in millions) Europe segment Generic products (including biosimilars) $4,044 $3,926 3%AJOVY 270 216 25%COPAXONE 181 213 (15%)Respiratory products 227 244 (7%)Other* 319 504 (37%)Total 5,040 5,103 (1%) *Other revenues in 2025 and 2024 include the sale of certain product rights. Year ended December 31, Percentage Change 2025 2024 2025-2024 (U.S.$ in millions) International Markets segment Generic products (including biosimilars) $1,721 $1,937 (11%)AJOVY 108 84 28%Austedo 43 46 (6%)COPAXONE 32 48 (34%)Other* 259 349 (26%)Total 2,162 2,463 (12%) *Other revenues in 2025 and 2024 include the sale of certain product rights. Free cash flow reconciliationUnaudited Three months ended December 31, 2025 2024 (U.S. $ in millions) Net cash provided by (used in) operating activities 1,158 575Beneficial interest collected in exchange for securitized account receivables 282 340Purchases of property, plant and equipment and intangible assets (142) (129)Proceeds from divestitures of businesses and other assets - 4Free cash flow$1,298 $790 Free cash flow reconciliationAudited Year ended December 31 2025 2024 (U.S. $ in millions) Net cash provided by (used in) operating activities 1,649 1,247Beneficial interest collected in exchange for securitized account receivables 1,214 1,291Purchases of property, plant and equipment and intangible assets (501) (498)Acquisition of businesses, net of cash acquired - (15)Proceeds from divestitures of businesses and other assets 34 43Free cash flow$2,396-$2,068 Net debt reconciliationAudited Year ended December 31, 2025 2024 (U.S. $ in millions) Short-term debt 1,820 1,781Senior notes and loans 14,986 16,002Total debt 16,807 17,783 Net of cash and cash equivalents 3,556 3,300 Net debt$13,251-$14,482

骨质疏松从来不是小病。在风湿免疫、内分泌、老年医学和骨科门诊，我们常见骨密度长期隐匿下降，最终以脆性骨折集中「爆雷」，带来功能丧失、再骨折和过早死亡等后果。到 2025 年，治疗已不再局限于「钙 + 维生素 D + 双膦酸盐」，多条通路的新药与序贯/联合策略推动治疗向个体化发展 [1]。 一  当前治疗格局：从经典到最新 01 抗骨吸收治疗（Antiresorptives） （1）双膦酸盐 [2] 双膦酸盐仍为多数情形下首选，代表药物包括阿仑膦酸盐、利塞膦酸盐、伊班膦酸盐和唑来膦酸等。其通过与骨羟基磷灰石结合，干扰破骨细胞的黏附、分化与存活，从而抑制骨吸收。口服制剂对胃肠耐受性有要求；对依从性差或有口服禁忌者，可选静脉唑来膦酸。长期用药需关注下颌骨坏死（MRONJ）和不典型股骨骨折（AFF），在用药 3~5 年后按个体风险评估是否考虑 「drug holiday」。 （2）地舒单抗（Denosumab） 地舒单抗是抗-RANKL 人源化单抗，每 6 个月皮下注射一次，给药方便且降骨折风险显著，适用于不能耐受口服双膦酸盐或肾功能不全患者。地舒单抗不掺入骨基质，其作用可逆，停药后可能出现快速的骨量丢失与反跳性骨折，因此务必在停药前预先安排序贯抗骨吸收治疗以巩固效果，并需按期注射以避免「漏针」。使用时还需监测血钙，肾功能不全患者尤其需注意低钙的风险。 （3）选择性雌激素受体调节剂（SERMs） 代表药物雷洛昔芬，可在骨组织发挥类雌激素作用，降低椎体骨折风险的同时可降低乳腺癌风险，但其会增加静脉血栓风险并可能加重潮热等症状，适用时需权衡利弊，主要考虑于需兼顾乳腺肿瘤风险的绝经后女性。 （4）激素替代治疗（HRT） HRT 在围绝经期或新绝经且合并明显更年期症状的女性既可缓解症状又能保护骨密度，但因可能增加乳腺癌、心血管事件与 VTE 风险，须严格个体化评估，不宜作为单纯骨保护的常规首选。 （5）降钙素（Calcitonin） 作用较弱，整体疗效不及上述药物，临床上多为无法耐受其他药物时的备选。 02 促成骨治疗（Anabolics）[3] 促成骨药物通过激活成骨通路直接增加新骨形成。 特立帕肽（teriparatide，PTH 1-34）与阿巴帕肽（abaloparatide）均为间断给药的 PTH/PTHrP 类药，能在数月内显著提升成骨标志物并增加 BMD，适用于严重骨质疏松、既往脆性骨折或糖皮质激素所致骨质疏松等高危人群。临床上应将总疗程限定在 24 个月以内，疗程结束后必须立即序贯抗骨吸收药以巩固骨量增益并维持骨折风险降低。使用促成骨药需监测血钙并评估患者是否能配合随后的长期巩固治疗。 03 双重作用药物 Romosozumab[4] 为抗 sclerostin 单抗，具有同时促进成骨和抑制骨吸收的 「双重作用」，在短期内对腰椎与髋部 BMD 的提升速度与幅度均较显著，适合骨折风险「非常高」的患者起始使用（例如近期脆性骨折或多发既往骨折、T ≤ −3.0 等）。Romosozumab 疗程通常限制为 12 个月，停用后需无缝接抗骨吸收药以维持获益。总体耐受性良好，但存在心血管事件增加的信号，既往 1 年内发生心肌梗死或脑卒中的患者禁用，心血管高危患者需谨慎评估。 04 联合与序贯治疗 （1）联合治疗（同时用两种） 理论上可利用促成骨与抗吸收药的互补机制以获得更快、更大 BMD 增益。临床研究显示【特立帕肽 ＋ 地舒】可在短期内显著提高腰椎与髋部 BMD，但【特立帕肽 ＋ 阿仑膦酸】未见叠加效果甚至可能抑制成骨反应。由于成本与管理复杂，联合治疗宜限于极高危或特殊病例。 （2）序贯治疗（先后衔接用药） 临床常用「先攻后守」策略：先用促成骨或 Romosozumab 快速建骨，随后紧接抗骨吸收药以维持增益。注意转换时机：长期口服双膦酸后再上促成骨，成骨反应可能减弱；由地舒直接转换为促成骨时髋部 BMD 可能短期下降，需个体化设计并密切监测。对近期骨折或 FRAX 高者，先促成骨 /Romosozumab 再接抗吸收药是当前证据支持的主要路径。 05 支持治疗 钙以饮食为主，目标 1000-1200 mg/日；维生素 D 800-1000 IU/日（建议缺乏者补充，治疗前及治疗中应监测血清 25 羟维生素 D 水平）。避免常规大剂量钙补，且需结合心血管风险综合评估。 运动以负重和抗阻训练为主，配合平衡训练与跌倒危险因素干预，按功能状态制定个体化方案。 二 炎症控制类生物制剂对骨的潜在益处 炎症与骨丢失密切相关：促炎细胞因子（TNF-α、IL-1、IL-6、IL-17 等）可上调 RANKL，促进破骨。对风湿病人群而言，抗炎治疗常能改善骨转换标志物并在一定程度上稳定或小幅提升 BMD，但目前证据不足以将这些药物作为专门的防骨折药 [5]。 01 TNF-α 抑制剂（阿达木单抗、依那西普、英夫利昔单抗） 可抑制炎症驱动的破骨过程。在类风湿关节炎等炎症性疾病中，使用 TNF 抑制剂后常见骨转换标志物下降和腰髋 BMD 稳定或略升。然而尚无确凿证据显示其能独立替代抗骨吸收或促成骨治疗以预防脆性骨折。 02 IL-6 抑制剂（托珠单抗） 阻断 IL-6 信号可降低骨吸收相关标志物（如 CTX），临床上在活动期类风湿患者中常见腰髋 BMD 稳定或小幅增加，ACPA 阳性亚组效应更明显。当前证据仍以「炎症控制后附带获益」为主，独立降低骨折的证据不足。 03 T 细胞共刺激阻断（阿巴西普） 通过抑制 T 细胞活化，阻断炎症级联的上游环节，间接影响 RANKL。真实世界队列提示 阿巴西普对 BMD 的保护或优于部分对照，可能是合并骨质疏松风险的 RA 患者的合理治疗考量之一。 04 B 细胞清除抗体（利妥昔单抗） B 细胞对骨代谢的作用复杂，既能产生促破骨因子（如 RANKL），也能产生抗吸收因子（如 OPG）。达到良好炎症控制者可见 RANKL 下降与 BMD 稳定，但病情波动时效果不一致，主要收益仍来自对原发炎症的控制。 05 IL-17 抑制剂（赛库奇珠单抗） 对脊柱关节病相关的局灶性骨破坏有保护潜力，系统性对抗骨质疏松的证据有限，临床上多表现为 BMD 稳定，作用更偏向控制局部炎性损害。 06 IL-23 抑制剂（ustekinumab、guselkumab、risankizumab） 通过下游抑制 Th17/IL-17 轴间接控制炎症，针对全身骨代谢的临床数据稀少，护骨效果多被视为炎症控制的二次结果。 07 JAK 抑制剂（tofacitinib、baricitinib、upadacitinib、filgotinib）[6] JAK 抑制剂可同时阻断多种促炎细胞因子的信号。基础研究提示可能有利于成骨，但临床数据混杂：部分研究显示骨转换标志物改善，药物监测数据（如 VigiBase）亦提示骨折报告率的安全信号，需警惕并继续观察真实世界结局。 08 IL-1β（canakinumab） 可降低骨吸收标志物，但临床证据有限，需更多研究确认对 BMD/骨折的实际益处。 综上，对于风湿免疫病患者，有效控制原发病的炎症活动是保护骨健康的基础。在炎症控制达标后，若患者仍属骨折高危人群，应依据通用的骨质疏松治疗指南启动或优化抗骨质疏松治疗，而非仅依赖生物制剂的『附带』护骨作用。 三  正在开发的新型治疗 01 Wnt 通路调节剂：Sclerostin 与 DKK1 抑制剂 [7] Sclerostin 抑制剂除了罗莫苏单抗外，blosozumab 在临床早期也显示出希望，在一项 120 例的 II 期试验中，皮下给药 1 年使腰椎 BMD 增加 17.7%、全髋 6.7%，但其后开发被终止，具体原因未披露。 DKK1 也是 Wnt 的内源性抑制子，阻断其可促进成骨。但需注意，全身性增强 Wnt 信号存在潜在致瘤等安全顾虑。 02 Strontium ranelate[8] 口服可降低绝经后妇女骨折风险，兼具抑骨吸收与促成骨作用，但与心血管事件、VTE 和罕见严重过敏反应相关，因在多国未获批，临床应用极为有限。 03 Cathepsin K 抑制剂 [9] 以 odanacatib 为代表，LOFT III 试验显示每周给药可降低各类骨折并增加 BMD，但延长期观察到卒中事件增多，导致开发终止，其它同类药物亦因安全性问题未推进。 04 Calcilytics 口服小分子模拟间歇 PTH 的促成骨效应，动物与早期研究有积极信号（成骨标志物与 BMD 提升），但 II 期试验未显示显著 BMD 提高，开发受挫。 05 基于 PTH 的新策略 在特立帕肽/阿巴帕肽基础上开发的新方向包括骨锚定（PTH-CBD）与长效前药（TransCon-PTH）等，目标是提高疗效与给药便利性 [10]。这些方案仍在临床验证阶段。 06 其他早期候选药物 包括 AChE 抑制剂、降钙素受体激动剂、天然产物（如 tiliroside）、NLRP3/TLR4 等炎症相关靶点，以及 FAP、FGF21、SIRT3、P2X7、基因/细胞疗法等，多数证据来自动物或早期研究，作用与适应症尚不明确，安全性为主要限制。 07 临床开发亮点 若干地舒单抗生物类似药已进入 II/III 期试验（如 CT-P41、RGB-14-P、QL1206、Bmab1000、AVT03、TVB-009 等），双特异性或新机制抗体（如同时抑制 sclerostin + DKK1 的 AGA2118）及改善给药方式的候选（如口服 PTH 类似物 EB613）在研。总体上，生物相似药可提升可及性，其它新药仍需更多抗骨折与安全数据支持。 四  总结 当前骨质疏松治疗的核心不再是「有没有药」，而是把「风险识别 → 药物档位选择 → 序贯/接力设计 → 规范监测」形成临床流程。风湿科患者天然高风险，我们的价值就在于早期识别极高危患者、及时给予促成骨或双重作用起始并妥善安排后续巩固，从而最大限度减少脆性骨折的发生。 Take-home message 风险分层后再用药：极高危先促成骨或罗莫尤单抗，疗程后立即接抗吸收药巩固。 药物安全性：Romosozumab 前评估心血管史；PTH 类/地舒单抗监测血钙；长期双膦酸盐注意 MRONJ 与 AFF。 疗效监测：DXA 按药物调整频率；骨转换标志物可作为早期反应指标。 地舒单抗停药管理：提前安排双膦酸盐接力，按时给药，防反跳性骨丢失和椎体骨折。 基础治疗不可少：保证充足钙 + 维 D，常规推荐负重/抗阻训练。 ✩ 本文仅供医疗卫生等专业人士参考 投稿邮箱：huanghaihua@dxy.cn 编辑：黄海花   题图来源：站酷海洛 参考资料： [1] Inderjeeth C, Inderjeeth DC. Novel therapies in osteoporosis - Clinical update - 2025. Best Pract Res Clin Rheumatol. Dec 2025;39(4):102100. doi:10.1016/j.berh.2025.102100 [2] Watts NB, Camacho PM, Lewiecki EM, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis-2020 Update. Endocr Pract. Apr 2021;27(4):379-380. doi:10.1016/j.eprac.2021.02.001 [3] Inderjeeth CA, Inderjeeth DC. The use of anabolic agents in the treatment of osteoporosis: a clinical update. Curr Opin Endocrinol Diabetes Obes. Aug 1 2024;31(4):157-163. doi:10.1097/med.0000000000000867 [4] McClung MR. Role of bone-forming agents in the management of osteoporosis. Aging Clin Exp Res. Apr 2021;33(4):775-791. doi:10.1007/s40520-020-01708-8 [5] Kim Y, Kim GT. Positive Effects of Biologics on Osteoporosis in Rheumatoid Arthritis. J Rheum Dis. 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Dec 2019;7(12):899-911. doi:10.1016/s2213-8587(19)30346-8 [10] Clarke BL, Khan AA, Rubin MR, et al. Efficacy and Safety of TransCon PTH in Adults With Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial. J Clin Endocrinol Metab. Mar 17 2025;110(4):951-960. doi:10.1210/clinem/dgae693