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Amgen hosted an investor event focused on its rare disease portfolio Thursday, but while Mizuho analysts found details from the meeting to be "only incrementally positive," they believe obesity – where the company recently gave an early glimpse at its AMG 133 candidate – "is still the more important story for 2024."AMG 133, also known as maridebart cafraglutide, is a bispecific molecule that activates GLP-1 and inhibits GIP. Earlier this month, results from a small, early-stage study published in Nature Metabolism showed that patients given a monthly injection of the drug lost up to 14.5% of their body weight in 12 weeks. Some people kept the weight off for up to 150 days after stopping the drug.The company's presentation instead focused on a pair of rare disease therapies – Tepezza (teprotumumab) for thyroid eye disease and Krystexxa (pegloticase) for gout – that it acquired through its $27.8-billion takeout of Horizon Therapeutics, while also spotlighting some clinical-stage pipeline assets.Expanding Tepezza internationally seem important for Amgen's growth, Mizuho analysts noted. In the US, reaching patients with low clinical activity scores and developing a subcutaneous form of the drug, where a pivotal Phase III programme is set to get underway in the first half, are expected to help it grow. Outside the country, Amgen said Japan and Europe are high-priority markets, with plans to file for approval in Europe in the first half of 2024 and to launch in Japan in 2025.Plenty of room for more uptakeAccording to Barclays analysts, Amgen struck an overall positive tone by highlighting the "high level [of] addressable patients" across its rare disease portfolio. The company estimates there are about 100,000 potential patients in the US who could benefit from Tepezza, but only a small percentage of them are using it at the moment. A similar story plays out for Krystexxa; although there are over 100,000 potential patients, Amgen pegs current uptake at only around 6000.It also emphasised three other programmes it expects will be key growth drivers – the CD40 ligand antagonist dazodalibep which recently entered Phase III for Sjögren's disease; the anti-ILT7 lupus candidate daxdilimab, and the LPA1 antagonist fipaxalparant. Amgen currently has a pair of Phase II studies evaluating fipaxalparant for idiopathic pulmonary fibrosis and systemic sclerosis. A readout from the first of these studies is due in the second half.Barclays noted that the company wouldn't discuss differentiation against Bristol Myers Squibb's own LPA1 drug obexelimab, but "highlighted the unmet need and confidence in the mechanism." Obexelimab, which simultaneously binds CD19 and FcγRIIb, is currently in Phase III for IgG4-related disease. Bristol Myers Squibb acquired regional rights to the drug from Zenas BioPharma for $50 million upfront last year.

THOUSAND OAKS, Calif., Feb. 6, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced financial results for the fourth quarter and full year 2023 versus comparable periods in 2022. "2023 was another year of performance and progress for our company," said Robert A. Bradway, chairman and chief executive officer. "Our marketed products are reaching many more patients around the world, and we anticipate more than a dozen significant pipeline milestones in 2024." Key results include: For the fourth quarter, total revenues increased 20% to $8.2 billion in comparison to the fourth quarter of 2022. Product sales grew 20%, driven by 23% volume growth, partially offset by 3% lower net selling price. Nine brands(1) achieved record sales in the quarter, and Repatha® (evolocumab), EVENITY® (romosozumab-aqqg), Prolia® (denosumab) and BLINCYTO® (blinatumomab) delivered double-digit volume growth globally. U.S. volume grew 26% and ex-U.S. volume grew 15%, including 46% volume growth in the Asia Pacific region. Our performance included $954 million of sales for the period of Oct. 6 - Dec. 31 from our recent Horizon Therapeutics (Horizon) acquisition, driven by several first-in-class, early-in-lifecycle medicines such as TEPEZZA® (teprotumumab-trbw), KRYSTEXXA® (pegloticase) and UPLIZNA® (inebilizumab-cdon). Excluding the impact of these sales from Horizon, our product sales grew 5%, driven by volume growth of 9%. For the full year, total revenues increased 7% to $28.2 billion, resulting from a 9% increase in product sales. Product sales growth was driven by 15% volume growth, partially offset by 3% lower net selling price, 1% unfavorable changes from estimated sales deductions and 1% negative impact from foreign exchange. GAAP earnings per share (EPS) decreased 53% from $3.00 to $1.42 in the fourth quarter, driven by acquisition-related expenses and incremental operating expenses from Horizon, partially offset by increased revenues. For the full year, GAAP EPS increased 3% from $12.11 to $12.49 driven by net gains on our BeiGene, Ltd equity investment in 2023 and higher revenues, partially offset by higher operating expenses, including acquisition-related expenses and incremental expenses from Horizon. For the fourth quarter, GAAP operating income decreased from $2.2 billion to $1.3 billion, and GAAP operating margin decreased 17.8 percentage points to 16.2%. For the full year, GAAP operating income decreased from $9.6 billion to $7.9 billion, and GAAP operating margin decreased 9.3 percentage points to 29.3%. Non-GAAP EPS increased 15% from $4.09 to $4.71 in the fourth quarter and increased 5% from $17.69 to $18.65 for the full year, driven by increased revenues, partially offset by higher operating expenses, including incremental expenses from Horizon. Fourth quarter non-GAAP EPS was also unfavorably impacted by higher interest expense. For the fourth quarter, non-GAAP operating income increased from $3.0 billion to $3.7 billion, and non-GAAP operating margin increased 0.8 percentage points to 46.7%. For the full year, non-GAAP operating income increased from $12.8 billion to $13.4 billion, and non-GAAP operating margin decreased 1.7 percentage points to 49.8%. The Company generated $7.4 billion of free cash flow for the full year versus $8.8 billion in 2022. The decrease in 2023 was primarily driven by transaction expenses related to the Horizon acquisition and higher repatriation tax payments. (1) Includes product sales for the full fourth quarter of 2023 from UPLIZNA and KRYSTEXXA in connection with Horizon acquisition. 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), "EBITDA, or earnings before interest, taxes, depreciation and amortization" (computed by adding interest expense, provision for income taxes, and depreciation and amortization expense to GAAP net income) and "debt leverage ratio" (calculated as the ratio of GAAP total debt to EBITDA) 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 20% for the fourth quarter of 2023 versus the fourth quarter of 2022. Volume grew 23%, partially offset by 3% lower net selling price. Full year product sales increased 9% versus 2022, driven by 15% volume growth, partially offset by 3% lower net selling price, 1% unfavorable changes from estimated sales deductions and 1% negative impact from foreign exchange. General Medicine Repatha® sales increased 25% year-over-year for the fourth quarter, driven by 35% volume growth, partially offset by lower net selling price. Full year sales increased 26%, driven by 37% volume growth, partially offset by lower net selling price. Repatha remains the global proprotein convertase subtilisin/kexin type 9 (PCSK9) segment leader, with over 2.5 million patients treated since launch. Prolia® sales increased 12% year-over-year, to a record $1.1 billion for the fourth quarter, and 12% for the full year, primarily driven by volume growth and higher net selling price. Volume grew 10% for the quarter and 9% for the full year. In 2023, over 7.5 million patients were treated with Prolia. EVENITY® sales increased 41% year-over-year to a record $318 million for the fourth quarter and 47% for the full year, driven by strong volume growth. U.S. volume grew 44% year-over-year and volume outside the U.S. grew 55% for the full year. Aimovig® (erenumab-aooe) sales decreased 32% year-over-year for the fourth quarter and 22% for the full year, driven by lower net selling price. Oncology BLINCYTO® sales increased 47% year-over-year to a record $241 million for the fourth quarter and 48% for the full year, driven by 55% and 49% volume growth, respectively. Volume growth was supported by broad prescribing across academic and community settings for patients with B-cell precursor acute lymphoblastic leukemia. Vectibix® (panitumumab) sales increased 5% year-over-year for the fourth quarter and 10% for the full year, driven by 5% and 10% volume growth, respectively. KYPROLIS® (carfilzomib) sales increased 8% year-over-year for the fourth quarter and 13% for the full year, driven by 8% and 12% volume growth, respectively. LUMAKRAS®/LUMYKRAS™ (sotorasib) sales increased 8% year-over-year for the fourth quarter, driven by 5% volume growth and higher net selling price. Full year sales decreased 2%, driven by unfavorable changes to estimated sales deductions, including changes related to ongoing reimbursement negotiations in France. Full year sales were also impacted by lower net selling price and lower inventory levels, partially offset by 16% volume growth. XGEVA® (denosumab) sales increased 9% year-over-year for the fourth quarter and 5% for the full year, primarily driven by higher net selling price. Nplate® (romiplostim) sales decreased 18% year-over-year for the fourth quarter, driven by volume decline related to timing of orders placed by the U.S. government, partially offset by volume growth across our U.S. and ex-U.S. regions. U.S. government orders were $207 million in Q4'22 compared to $62 million in Q4'23. Full year sales increased 13%, primarily driven by volume growth, including U.S. government orders. U.S. government orders were $207 million for FY'22 compared to $286 million for FY'23. Excluding these U.S. government orders, Nplate sales grew 23% year-over-year for the fourth quarter and 8% for the full year. MVASI® (bevacizumab-awwb) sales decreased 8% year-over-year for the fourth quarter, primarily driven by lower net selling price, partially offset by 12% volume growth. Full year sales decreased 11%, primarily driven by lower net selling price, partially offset by 13% volume growth. Going forward, we expect continued net selling price erosion driven by increased competition. KANJINTI® (trastuzumab-anns) sales decreased 33% year-over-year for the fourth quarter and 50% for the full year, driven by lower net selling price and volume decline. Inflammation TEZSPIRE® (tezepelumab-ekko) generated $177 million of sales in the fourth quarter. Quarter-over-quarter sales increased 10%, driven by 18% volume growth that benefited from the pre-filled, single-use pen, which was approved for self-administration by the U.S. Food and Drug Administration (FDA) in the first quarter. Healthcare providers recognize TEZSPIRE's unique, differentiated profile and its broad potential to treat the 2.5 million patients worldwide with severe asthma who are uncontrolled, without any phenotypic or biomarker limitation. Otezla® (apremilast) sales increased 2% year-over-year for the fourth quarter, driven by favorable changes to estimated sales deductions and 3% volume growth, partially offset by lower inventory levels and lower net selling price. Full year sales decreased 4%, driven by lower net selling price and lower inventory levels, partially offset by 2% volume growth. We expect future growth for Otezla to be driven by its established efficacy and safety profile, strong payer coverage with limited prior authorization requirements and ease of administration. Otezla remains the only approved oral systemic therapy with a broad indication and is well-positioned to help the 1.5 million U.S. patients with mild-to-moderate psoriasis who cannot be optimally addressed by a topical and can benefit from a systemic treatment like Otezla. Enbrel® (etanercept) sales decreased 8% year-over-year for the fourth quarter, driven by a 4% impact from unfavorable changes to estimated sales deductions and lower net selling price. Full year sales decreased 10%, driven by lower net selling price, lower inventory levels and a 3% impact from unfavorable changes to estimated sales deductions. Year-over-year volume remained flat, with U.S. volume growing 1% in the fourth quarter, supported by an increase in new patients starting treatment as a result of improved payer coverage. Going forward, we expect net selling price to continue to decline year-over-year, driven by higher rebates to maintain broad first-line payer coverage and changes in patient mix. We expect Otezla and Enbrel to follow the historical pattern of lower sales in the first quarter relative to subsequent quarters due to the impact of benefit plan changes, insurance reverification and increased co-pay expenses as U.S. patients work through deductibles. AMJEVITA®/AMGEVITA™ (adalimumab) sales increased 34% year-over-year for the fourth quarter and 36% for the full year, primarily driven by 35% and 46% volume growth, respectively. Ex-U.S. sales increased 9% for the full year, driven by 20% volume growth, partially offset by lower net selling price. U.S. sales increased 43% quarter-over-quarter, driven by higher inventory levels and higher net selling price, partially offset by volume decline. Rare Disease Excluding TAVNEOS®, the products listed below were acquired from our Horizon transaction on Oct. 6, 2023. Sales figures reflect only sales in the period from Oct. 6 2023 through the end of the year, and not the full quarter. TEPEZZA® (teprotumumab-trbw) generated $448 million of sales for the period. TEPEZZA is the first and only FDA-approved treatment for thyroid eye disease (TED). KRYSTEXXA® (pegloticase) generated $272 million of sales for the period. KRYSTEXXA is the first and only FDA-approved treatment for chronic refractory gout. UPLIZNA® (inebilizumab-cdon) generated $65 million of sales for the period. UPLIZNA is used to treat adults with neuromyelitis optica spectrum disorders (NMOSD). TAVNEOS® (avacopan) generated $44 million of sales in the fourth quarter. Quarter-over-quarter sales increased 19%, primarily driven by volume growth. U.S. volume grew 23% quarter-over-quarter. In the U.S., approximately 2,700 patients have now been treated with TAVNEOS. Ultra rare products, which consist of RAVICTI® (glycerol phenylbutyrate), PROCYSBI® (cysteamine bitartrate), ACTIMMUNE® (interferon gamma-1b), BUPHENYL® (sodium phenylbutyrate) and QUINSAIR® (levofloxacin) generated $164 million of sales for the period. Established Products Total sales of our established products, which consist of EPOGEN® (epoetin alfa), Aranesp® (darbepoetin alfa), Parsabiv® (etelcalcetide) and Neulasta® (pegfilgrastim), decreased 10% year-over-year for the fourth quarter, primarily driven by lower net selling price and volume declines, partially offset by favorable changes to estimated sales deductions. Full year sales decreased 19%, driven by lower net selling price and volume declines. In the aggregate, we expect the year-over-year net selling price and volume declines for this portfolio of products to continue. Product Sales Detail by Product and Geographic Region Operating Expense, Operating Margin and Tax Rate Analysis On a GAAP basis: Total Operating Expenses increased 50% year-over-year for the fourth quarter. For the full year, Total Operating Expenses increased 21%. Cost of Sales as a percentage of product sales increased 13.0 percentage points in the fourth quarter primarily driven by higher amortization expense from acquisition-related assets as well as higher profit share and royalties, partially offset by Puerto Rico excise tax, changes in product mix, and lower manufacturing cost. For the full year, cost of sales as a percentage of product sales increased 5.6 percentage points primarily driven by higher amortization expense from acquisition-related assets, higher profit share and royalties, and changes in product mix, partially offset by Puerto Rico excise tax. Research & Development (R&D) expenses increased 16% in the fourth quarter and increased 8% for the full year driven by higher spend in later-stage clinical programs and marketed products support, including spend from programs acquired from the Horizon acquisition. Selling, General & Administrative (SG&A) expenses increased 45% in the fourth quarter and increased 14% for the full year primarily driven by higher acquisition-related costs, in addition to commercial and general administrative expenses related to the Horizon acquisition. For the full year, this was partially offset by a decline in other marketed product spend. Other operating expenses for the full year consisted of net impairment charges for AMG 340 and Teneobio IPR&D assets in addition to expenses related to our restructuring plan initiated in the first quarter of 2023. Operating Margin as a percentage of product sales decreased 17.8 percentage points to 16.2% in the fourth quarter and decreased 9.3 percentage points for the full year to 29.3%. Tax Rate increased 2.4 percentage points in the fourth quarter and increased 3.7 percentage points for the full year, primarily driven by the 2022 Puerto Rico tax law change that replaced the excise tax with an income tax beginning in 2023. For the fourth quarter this was partially offset by the change in earnings mix. On a non-GAAP basis: Total Operating Expenses increased 18% for the fourth quarter and increased 9% for the full year. Cost of Sales as a percentage of product sales remained flat in the fourth quarter primarily driven by higher profit share and royalties, offset by Puerto Rico excise tax, changes in product mix, and lower manufacturing cost. For the full year, cost of sales as a percentage of product sales increased 1.1 percentage points primarily driven by higher profit share and royalties and changes in product mix, partially offset by Puerto Rico excise tax. R&D expenses increased 16% in the fourth quarter and increased 8% for the full year driven by higher spend in later-stage clinical programs and marketed products support, including spend from programs acquired from the Horizon acquisition. SG&A expenses increased 20% in the fourth quarter and increased 5% for the full year primarily driven by higher commercial and general administrative expenses related to the Horizon acquisition. For the full year, this was partially offset by a decline in other marketed product spend. Operating Margin as a percentage of product sales increased 0.8 pts. percentage points to 46.7% in the fourth quarter and decreased 1.7 percentage points for the full year to 49.8%. Tax Rate increased 2.5 percentage points in the fourth quarter and increased 2.7 percentage points for the full year primarily due to the 2022 Puerto Rico tax law change that replaced the excise tax with an income tax beginning in 2023. Cash Flow and Balance Sheet The Company generated $0.3 billion of free cash flow in the fourth quarter of 2023 versus $2.3 billion in the fourth quarter of 2022, primarily driven by timing of federal and repatriation tax payments. The Company generated $7.4 billion of free cash flow for the full year 2023 versus $8.8 billion in 2022. The Company's fourth quarter 2023 dividend of $2.13 per share was declared on October 24, 2023, and was paid on December 8, 2023, to all stockholders of record as of November 17, 2023, representing a 10% increase from 2022. During the fourth quarter, there were no repurchases of shares of common stock. Cash and investments totaled $10.9 billion and debt outstanding totaled $64.6 billion as of December 31, 2023. Debt leverage was approximately 4.4 times EBITDA as of December 31, 2023. 2024 Guidance For the full year 2024, the Company expects: Total revenues in the range of $32.4 billion to $33.8 billion. On a GAAP basis, EPS in the range of $8.42 to $9.87, and a tax rate in the range of 11.5% to 13.0%. On a non-GAAP basis, EPS in the range of $18.90 to $20.30, and a tax rate in the range of 16.0% to 17.0%. Capital expenditures to be approximately $1.1 billion. Share repurchases not to exceed $500 million. Fourth Quarter Product and Pipeline Update The Company provided the following updates on selected product and pipeline programs: General Medicine Maridebart cafraglutide (AMG 133) A Phase 2 study of maridebart cafraglutide, a multispecific molecule that inhibits the gastric inhibitory polypeptide receptor (GIPR) and activates the glucagon like peptide 1 (GLP-1) receptor, in overweight or obese adults with or without type 2 diabetes mellitus has completed enrollment, with topline data anticipated in late 2024. The Company recently added a Part 2 to this study which explores durable weight loss beyond 52 weeks. Planning for a comprehensive Phase 3 program across multiple indications remains on track. In February 2024, results of preclinical studies and the Phase 1 study of maridebart cafraglutide were published in Nature Metabolism. AMG 786 A Phase 1 study of AMG 786, a small molecule obesity program, is ongoing with initial data readout anticipated in H1 2024. This molecule has a different target than maridebart cafraglutide and is not an incretin-based therapy. Olpasiran (AMG 890) A Phase 3 cardiovascular outcomes study of olpasiran, a potentially best-in-class small interfering ribonucleic acid (siRNA) molecule that reduces lipoprotein(a) (Lp(a)) synthesis in the liver, in patients with atherosclerotic cardiovascular disease and elevated Lp(a) continues to enroll patients. To date, over 7,000 patients have been enrolled, with enrollment completion anticipated in H1 2024. Repatha EVOLVE-MI, a Phase 4 study of Repatha administered within 10 days of an acute myocardial infarction to reduce the risk of cardiovascular events, continues to enroll patients. A Phase 3 cardiovascular outcomes study (VESALIUS-CV) in patients at high cardiovascular risk without prior myocardial infarction or stroke is ongoing. Oncology Tarlatamab (AMG 757) The U.S. Food and Drug Administration (FDA) has granted Priority Review for the Company's Biologics License Application (BLA) for tarlatamab, a first-in-class investigational delta-like ligand 3 (DLL3) targeting BiTE® (bispecific T-cell engager) molecule. The BLA is based on the results from the Phase 2 DeLLphi-301 clinical trial, which demonstrated antitumor activity with a durable response and encouraging survival outcomes in previously treated small cell lung cancer (SCLC). The safety profile was consistent with the Phase 1 trial. Based on the Priority Review designation, the Prescription Drug User Fee Act (PDUFA) date for tarlatamab is June 12, 2024. DeLLphi-304, a Phase 3 study comparing tarlatamab with standard of care chemotherapy in second-line SCLC, continues to enroll patients. DeLLphi-306, a Phase 3 study comparing tarlatamab with placebo in limited-stage SCLC, was initiated. DeLLphi-305, a Phase 3 study comparing tarlatamab and durvalumab with durvalumab alone in first-line, extensive-stage SCLC, will be initiated in H1 2024. DeLLphi-300, a Phase 1 study of tarlatamab in relapsed/refractory SCLC, continues to enroll patients. DeLLphi-302, a Phase 1b study of tarlatamab in combination with AMG 404, an anti-programmed cell death protein 1 (PD1) monoclonal antibody, in second-line or later SCLC, is ongoing.   DeLLphi-303, a Phase 1b study of tarlatamab in combination with standard of care in first-line SCLC, continues to enroll patients. DeLLpro-300, a Phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer, is ongoing. BLINCYTO The FDA granted Priority Review for the Company's supplemental BLA for BLINCYTO in early-stage, CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) based in part on the Phase 3 E1910 study conducted by the National Cancer Institute, the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network Cancer Research Group. Based on the Priority Review designation, the PDUFA date for BLINCYTO is June 21, 2024. Additional global regulatory authority submissions are underway. Golden Gate, a Phase 3 study of BLINCYTO alternating with low-intensity chemotherapy in older adults with newly diagnosed Philadelphia chromosome-negative (Ph-) B-ALL, continues to enroll patients. The Company is planning to amend the Golden Gate Phase 3 study to include an evaluation of blinatumomab subcutaneous administration with initiation anticipated in H2 2024. A Phase 1/2 study of subcutaneous blinatumomab in adults with relapsed or refractory Ph- B-ALL continues to enroll patients. Xaluritamig (AMG 509) A Phase 1b monotherapy and combination dose-escalation and -expansion study of xaluritamig, a first-in-class bispecific T-cell engager targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1) in metastatic castrate resistant prostate cancer continues to enroll patients in the dose-expansion portion of the study, where enrollment is almost complete. A reduced monitoring cohort was also initiated. Two additional Phase 1 studies of xaluritamig to evaluate preliminary efficacy and safety in patients with early prostate cancer are planned. AMG 193 The Phase 1/1b/2 study of AMG 193, a first-in-class small molecule methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, continues to enroll patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors. To date, responses have been seen in nine patients across seven tumor types. Master protocols in thoracic and gastrointestinal malignancies exploring combinations with standard of care will be initiated in H1 2024. A Phase 1/2 study of AMG 193 in combination with IDE397, an investigational methionine adenosyltransferase 2A (MAT2A) inhibitor, is enrolling patients. Nplate A Phase 3 study of Nplate in chemotherapy-induced thrombocytopenia in gastrointestinal, pancreatic, or colorectal malignancies is fully enrolled. Data readout is anticipated in H2 2024. LUMAKRAS/LUMYKRAS A U.S. regulatory submission is planned for the Phase 3 CodeBreaK 300 trial in H1 2024. This study evaluated two doses of LUMAKRAS (960 mg or 240 mg) in combination with Vectibix in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer (CRC). A Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI in first-line KRAS G12C-mutated CRC was initiated. A Phase 3 study of LUMAKRAS plus chemotherapy vs. pembrolizumab plus chemotherapy in first-line KRAS G12C-mutated and programmed cell death protein ligand-1 (PD-L1) negative advanced non-small cell lung cancer (NSCLC) is enrolling patients. Regulatory review by the European Medicines Agency (EMA) of the CodeBreaK 200 Phase 3 trial of adults with previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC along with data from the Phase 2 dose-comparison substudy is ongoing. The FDA completed its review of the Company's supplemental New Drug Application seeking full approval of LUMAKRAS based on the CodeBreaK 200 trial results. The FDA issued a new postmarketing requirement for an additional confirmatory study to support full approval to be completed no later than February 2028, while also concluding that LUMAKRAS at 960 mg once-daily will remain the dose for patients with KRAS G12C-mutated NSCLC under accelerated approval. Bemarituzumab FORTITUDE-101, a Phase 3 study of bemarituzumab, a first-in-class fibroblast growth factor receptor 2b (FGFR2b) targeting monoclonal antibody, plus chemotherapy in first-line gastric cancer, continues to enroll patients. FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab in first-line gastric cancer, continues to enroll patients in the Phase 3 portion of the study. FORTITUDE-103, a Phase 1b/2 study of bemarituzumab plus oral chemotherapy regimens with or without nivolumab in first-line gastric cancer, continues to enroll patients. FORTITUDE-301, a Phase 1b/2 basket study of bemarituzumab monotherapy in solid tumors with FGFR2b overexpression, is ongoing. Inflammation TEZSPIRE In severe asthma, the WAYFINDER Phase 3b study is fully enrolled. The PASSAGE Phase 4 real-world effectiveness study and the SUNRISE Phase 3 study continue to enroll patients. A Phase 3 study of TEZSPIRE in chronic rhinosinusitis with nasal polyps is fully enrolled. Primary analysis is anticipated in H2 2024. A Phase 3 study of TEZSPIRE in eosinophilic esophagitis continues to enroll patients. A Phase 2 study of TEZSPIRE in chronic obstructive pulmonary disease is fully enrolled. Data readout is anticipated in H1 2024. Rocatinlimab (AMG 451/KHK4083) The ROCKET Phase 3 program, now composed of eight studies evaluating rocatinlimab, a first in class monoclonal antibody targeting OX40, in moderate to severe atopic dermatitis, continues to enroll adult and adolescent patients. To date, over 2,400 patients have been enrolled in the ROCKET program. The Phase 3 HORIZON study (part of the ROCKET program) evaluating rocatinlimab monotherapy vs. placebo in adults with moderate to severe atopic dermatitis is fully enrolled. Data readout is anticipated in H2 2024. A Phase 2 study of rocatinlimab in asthma will be initiated in H1 2024 and a Phase 3 study of rocatinlimab in prurigo nodularis will be initiated in H2 2024. Otezla In November 2023, data were presented from the MOSAIC and FOREMOST studies: In the MOSAIC Phase 4 study, primary and key secondary outcomes highlighted that Otezla led to better inflammatory disease control in psoriatic arthritis patients with moderate clinical disease activity than in patients with high disease activity. In the FOREMOST Phase 4 study, Otezla when added to standard of care, significantly improved disease activity in patients with early oligoarticular (few joints involved) psoriatic arthritis at 16 weeks compared to placebo. Efavaleukin alfa (AMG 592) A Phase 2b study of efavaleukin alfa, an interleukin 2 (IL 2) mutein Fc fusion protein, in ulcerative colitis continues to enroll patients. Ordesekimab (AMG 714/PRV-015) A Phase 2b study of AMG 714, a monoclonal antibody that binds interleukin-15, in nonresponsive celiac disease has completed enrollment. Rare Disease TAVNEOS In November 2023, data were presented from the Phase 3 ADVOCATE trial demonstrating that outcomes in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis favored TAVNEOS versus a prednisone taper across subgroups of patients 65 years and older, patients with kidney involvement and albuminuria, and patients with diffuse alveolar hemorrhage at baseline. TEPEZZA In December 2023, TEPEZZA received orphan drug designation in Japan for patients with moderate to severe active thyroid eye disease (TED). A New Drug Application was submitted for TEPEZZA in Japan based on the results from the OPTIC-J study evaluating TEPEZZA in patients with active TED. A Phase 3 study of TEPEZZA in Japan for chronic or low clinical activity score (CAS) TED continues to enroll patients. The Company plans to initiate a Phase 3 study evaluating the subcutaneous route of administration of TEPEZZA in patients with TED in H1 2024. UPLIZNA A Phase 3 study of UPLIZNA in myasthenia gravis is fully enrolled. Data readout is anticipated in H2 2024. A Phase 3 study of UPLIZNA for the prevention of flare in immunoglobulin G4- (IgG4) related disease is fully enrolled. Data readout is anticipated in H2 2024. Dazodalibep A Phase 3 study of dazodalibep, a cluster of differentiation 40 (CD40) ligand inhibitor fusion protein in Sjögren's syndrome is enrolling patients. Daxdilimab A Phase 2 study of daxdilimab, a fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7), in moderate-to-severe active primary discoid lupus erythematosus refractory to standard of care is enrolling patients. A Phase 2 study of daxdilimab in dermatomyositis and antisynthetase inflammatory myositis is enrolling patients. Fipaxalparant (formerly AMG 670 / HZN 825) A Phase 2 study of fipaxalparant, a lysophosphatidic acid receptor 1 (LPAR1) antagonist, in idiopathic pulmonary fibrosis is enrolling patients. Data readout is anticipated in H2 2024. A Phase 2 study of fipaxalparant in diffuse cutaneous systemic sclerosis is enrolling patients. Biosimilars The clinical comparative study portion of a randomized, double-blind pivotal study evaluating pharmacokinetic (PK) similarity of ABP 206 compared with OPDIVO® (nivolumab) in resected stage III or stage IV melanoma patients in the adjuvant setting is enrolling patients. 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, a Sanofi Company. For the purposes of the collaboration, Provention Bio conducts a clinical trial and leads certain development and regulatory activities for the program. Xaluritamig, formerly AMG 509, is being developed pursuant to a research collaboration with Xencor, Inc. IDE397 is an investigational MAT2A inhibitor from IDEAYA Biosciences. OPDIVO is a registered trademark of Bristol-Myers Squibb Company. Non-GAAP Financial Measures In this news release, management has presented its operating results for the fourth quarters and full years 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 2024 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. Management has presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the fourth quarters and full years 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 Earnings Before Interest, Taxes, Depreciation and Amortization (EBITDA) and debt leverage ratio for 2023, both of which are non-GAAP financial measures. EBITDA is computed by adding interest expense, provision for income taxes, and depreciation and amortization expense to GAAP net income. Debt leverage ratio is calculated as the ratio of GAAP total debt to EBITDA. 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 normal and recurring business activities by facilitating comparisons of results of normal and recurring 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 its debt leverage ratio provides a supplemental operating metric for the full year period as it compares the amount of cash generated by our operations for the year. 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 2023, Amgen was named one of "America's Greatest Workplaces" by Newsweek, one of "America's Climate Leaders" by USA Today and one of the "World's Best Companies" by TIME. For more information, visit Amgen.com and follow us on X (formerly known as Twitter), LinkedIn, Instagram, TikTok, YouTube and Threads. 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. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon (including the prospective performance and outlook of Horizon's business, performance and opportunities and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this 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. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. ### CONTACT: Amgen, Thousand Oaks Jessica Akopyan, 805-440-5721 (media) Justin Claeys, 805-313-9775 (investors) * The known adjustments are presented net of their related tax impact, which amount to approximately $2.60 per share. (a) The adjustments include noncash amortization of intangible assets and fair value step-up of inventory acquired in business combinations. 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, asset impairments, litigation, changes in fair value of our contingent consideration obligations and changes in fair value of our equity investments. SOURCE Amgen

“全球药物研发进展一周速递”精选本周新药研发领域最新动态，新药研发进展、竞争格局、前沿技术等信息一文速览。药物研发进展1.泽璟制药重组人促甲状腺激素III期研究成功，拟申报上市9月18日，泽璟制药发布公告，其自主研发的注射用重组人促甲状腺激素（rhTSH）对比停服甲状腺激素疗法用于分化型甲状腺癌患者术后辅助诊断的III期ZGTSH004研究达到主要终点。注射用重组人促甲状腺激素（rhTSH）是泽璟制药自主研发的生物大分子药物，属于治疗用生物制品。人体内源性的促甲状腺激素是糖蛋白激素家族成员，主要在人垂体表达、分泌入血并和表达于甲状腺细胞和高分化的甲状腺癌细胞表面的hTSHR蛋白结合，可刺激碘摄取和有机化，以及甲状腺球蛋白（Tg）、三碘甲状腺原氨酸（T3）和甲状腺素（T4）的合成和释放。rhTSH与人天然TSH氨基酸序列完全一致。rhTSH激活甲状腺细胞的效应是增加放射碘的摄取，可以扫描检测或者放射碘杀伤甲状腺癌细胞。rhTSH激活也可以导致甲状腺细胞释放甲状腺球蛋白，甲状腺球蛋白是血液标本中甲状腺癌的肿瘤标志物。ZGTSH004研究是一项开放、单臂、自身对照、多中心的III期临床研究，在中国医学科学院北京协和医院、河南省肿瘤医院等研究中心开展，这项临床试验主要目的是评价分化型甲状腺癌术后辅助诊断131I全身显像（WBS）中，使用rhTSH处理的显像效果不劣于甲状腺激素撤除疗法（THW）。 结果显示，该研究有效性和安全性结果符合预期，达到方案预设的主要终点。泽璟制药将向CDE递交Pre-BLA的沟通交流申请，推进注射用重组人促甲状腺激素的上市进程。有关该项研究的详细数据，后续将在国际或国内临床学术会议上公布。2.百时美施贵宝创新分子胶iberdomide在中国启动3期临床9月18日，中国药物临床试验登记与信息公示平台官网公示，百时美施贵宝公司及旗下新基（Celgene）公司在中国启动了iberdomide胶囊的国际多中心3期临床研究，针对适应症为新诊断的多发性骨髓瘤。公开资料显示，iberdomide是一款靶向Ikaros/Aiolos（IKZF1/3）的蛋白降解疗法，也是一款基于度胺类分子进一步优化产生的分子胶类化合物。多发性骨髓瘤（MM）是一种危及生命的血癌，它是由于骨髓中的浆细胞癌变影响正常血细胞的生成，导致血细胞指数下降、骨骼和肾脏损伤。多发性骨髓瘤的主要治疗方案包括化疗、免疫调节药物（IMiDs，如来那度胺）和/或蛋白酶体抑制剂（PIs，如硼替佐米）联合或不联合干细胞移植。尽管有可用的治疗方法，MM仍然是一种无法治愈的恶性肿瘤，并且与显著的患者负担相关。公开资料显示，百时美施贵宝公司的蛋白稳态（Protein Homeostasis）技术平台使用多种不同的方法来达到降解靶标蛋白的效果，其中包括被称为CELMoD的分子胶类化合物。它们通过与E3泛素连接酶Cereblon结合，改变其底物特异性，让它能够标记与癌症相关的蛋白，促使它们降解。其中，基于度胺类分子进一步优化产生的多款CELMoD已经进入临床开发阶段，包括本次在中国启动临床的iberdomide（CC-220）。来那度胺和泊马度胺已经是治疗多发性骨髓瘤的常用免疫调节药物。研究人员发现，这两种度胺类分子抗癌的作用机制之一是与E3连接酶Cereblon结合，导致与癌症相关的蛋白的降解。基于这一机理进一步优化开发的CELMoD与Cereblon结合后，能够促进对IKZF1/3蛋白的降解，不但提高肿瘤“自杀”的活性，而且刺激效应免疫细胞的增殖。3.常山药业每周1次GLP-1R激动剂艾本那肽两项III期研究成功9月18日，常山药业发布公告，宣布每周1次艾本那肽（CJC-1134-PC）治疗糖尿病的两项III期研究达到主要终点。艾本那肽是常山凯捷健开发的一种长效胰高血糖素样肽-1受体激动剂（GLP-1RA），是利用药物亲和力偶合物（DACTM）技术，将艾塞那肽进行化学修饰后，与重组人血白蛋白结合形成的一个全新且稳定的化合物。常山凯捷健为常山药业与美国ConjuChem LLC公司设立的合资公司，目的是将ConjuChem LLC拥有的DAC技术平台及包括艾本那肽在内的在研产品的亚太地区所有权转移到中国，并实现药品的注册销售。常山药业持有常山凯捷健51%股份。试验方案编号为CSCJC DM301的研究是一项多中心、随机、双盲、安慰剂对照III期临床试验，旨在评价艾本那肽在接受二甲双胍单药或二甲双胍联合胰岛素促泌剂治疗后血糖控制不佳的2型糖尿病患者中的有效性和安全性。主要疗效分析提示，试验组和安慰剂组双盲治疗24周后，统计数据表明试验组相对于安慰剂组的优效性成立。次要疗效分析结果显示，艾本那肽可提高接受二甲双胍单药或二甲双胍联合胰岛素促泌剂治疗后血糖控制不佳的2型糖尿病患者的HbA1c达标率，维持HbA1c在目标水平。安全性方面，艾本那肽在这类2型糖尿病患者中具有较好的安全性，未出现新增的非预期安全性风险，与其他GLP-1RA的安全性特征基本一致。4.麓鹏制药新一代BTK抑制剂获批关键注册2期临床9月18日，麓鹏制药宣布，该公司核心产品新一代BTK抑制剂LP-168治疗既往接受过含CD20单抗免疫化疗方案和BTK抑制剂治疗后复发或难治的套细胞淋巴瘤（R/R MCL）的关键性注册2期临床研究（ROCK-1研究）获得中国国家药监局药品审评中心（CDE）批准。据悉，基于LP-168在1期研究中获得的安全性和有效性数据，CDE同意以ROCK-1研究为关键性注册研究支持LP-168在目标人群中的附条件上市申请。套细胞淋巴瘤（MCL）是一种严重威胁患者生命的疾病。BTK抑制剂（BTKi）的应用是近些年R/R MCL治疗上重要的进展。相对于传统化疗，BTKi治疗R/R MCL缓解率较高，安全性较好。然而，共价结合的BTK抑制剂（cBTKi）不能根治MCL，绝大部分患者终将出现疾病进展，耐药问题日趋显著。cBTKi治疗后的R/R MCL患者的生命受到疾病极其严重的威胁，该领域具有极高的未被满足的医疗需求，亟待新型药物的研发。LP-168是麓鹏制药自主研发的具有高活性、超高选择性的新一代口服BTKi，兼具以共价和非共价方式结合靶点的能力。临床前数据显示，LP-168可以克服共价结合的BTK抑制剂（cBTKi）的获得性耐药。LP-168在中国和美国同步开展早期临床研究，已在多种B细胞淋巴瘤中观察到显著的疗效，如MCL等。本次获批的ROCK-1研究是一项开放性、多中心的单臂2期临床研究，用以评价LP-168在R/R MCL患者中的有效性和安全性，主要终点指标为总体缓解率（ORR）。5.创新疗法2期试验完成首例患者给药9月18日，NeuroBo Pharmaceuticals宣布其在研新型G-蛋白偶联受体119（GPR119）激动剂DA-1241用于治疗非酒精性脂肪性肝炎（NASH）的2a期临床试验已完成首例患者给药。该试验设计分成两部分，预计在2024年上半年可进行中期分析，并预计在2024下半年获得完整数据。NASH是非酒精性脂肪性肝病（NAFLD）的更晚期形式。据估计，全球超过20%的成年人患有NAFLD。NASH是导致肝脏相关死亡的主要原因，对全球卫生系统造成日益加重的负担。此外，NASH患者，特别是那些具有更多代谢风险因素（高血压、合并2型糖尿病）的患者，心血管不良事件的风险增加，发病率和死亡率也相应提高。一旦NASH发展为显著的肝纤维化（F2和F3阶段），患者产生不良肝损伤结果的风险急剧上升。DA-1241是一种新型GPR119激动剂，开发作为NASH和2型糖尿病的单药或联合疗法。临床前研究证明，DA-1241可促进关键肠肽GLP-1、GIP和PYY的释放，对肝脏炎症、脂质代谢、体重减轻和葡萄糖代谢具有潜在益处。该公司已在多个NASH和2型糖尿病临床前动物模型中证实DA-1241的治疗潜力，其中DA-1241可减少肝脏脂肪变性、肝脏炎症和肝纤维化，同时改善血糖控制。此外，在1a期和1b期试验中，DA-1241在健康志愿者和2型糖尿病患者中均展现良好的耐受性。DA-1241临床2a期试验的两部分均设计为多中心、随机双盲、安慰剂对照、平行临床试验，为期16周，旨在评估DA-1241在可能推测患有NASH的病患和2型糖尿病前期或确诊为2型糖尿病患者中的疗效和安全性。6.恒瑞医药阿帕替尼2期临床获积极结果9月18日，恒瑞医药发布新闻稿称，其创新药阿帕替尼治疗复发或转移性腺样囊性癌的一项跨国多中心2期研究成果发表于Clinical Cancer Research（CCR）。结果显示，试验组盲法独立审查委员会（BIRC）评估的客观缓解率（ORR）为9.7%，研究者评估的ORR为15.3%，中位无进展生存期（mPFS）为9.0个月，中位总生存期（mOS）未达到，整体安全性可控。这为阿帕替尼治疗复发或转移性腺样囊性癌提供了新依据。腺样囊性癌（ACC）是起源于分泌腺的罕见肿瘤，常见于唾液腺。原发肿瘤切除和放疗后，局部和远处复发很常见，其中肺外远处转移以及诊断复发/转移（R/M）后3年内需要治疗的患者生存期明显缩短。因此，探索有效且安全的治疗复发或转移腺样囊性癌的方案很有必要。阻断血管内皮生长因子受体（VEGFRs）的多靶点酪氨酸激酶抑制剂（TKIs）的研究显示出积极前景。同时，在ACC的手术切除标本和转移ACC的细胞系中，VEGFR表达广泛。阿帕替尼是口服的选择性靶向VEGFR2的TKI。该药目前有3个适应症获批，分别为单药用于晚期胃腺癌或胃-食管结合部腺癌、既往接受过至少一线系统性治疗后失败或不可耐受的晚期肝细胞癌、联合卡瑞利珠单抗用于不可切除或转移性肝细胞癌。此次发表的研究是一项开放标签、单臂、多中心的2期临床试验，由加利福尼亚大学旧金山分校Hyunseok Kang教授牵头开展，旨在评估阿帕替尼治疗复发/转移腺样囊性癌的有效性和安全性。试验主要终点是研究者及BIRC评估的ORR，关键次要终点包括缓解持续时间（DOR）、无进展生存期（PFS）、总生存期（OS）和安全性。研究结果显示，2020年1月至2021年5月，共招募80例受试者，可以评估其中72例受试者的有效性。研究者评估11例患者达到部分缓解（PR），ORR达15.3%。BIRC评估7例患者达到PR，ORR为9.7%。7.欧加隆降脂复方制剂依折麦布阿托伐他汀钙片在华获批9月19日，欧加隆（Organon）中国宣布，其心血管领域创新复方制剂益立妥（依折麦布阿托伐他汀钙片(Ⅰ)/(Ⅱ)）获得中国国家药品监督管理局（NMPA）上市许可批准，用于治疗高胆固醇血症和纯合子型家族性高胆固醇血症（HoFH）。高胆固醇血症作为动脉粥样硬化性心血管疾病（ASCVD）重要的危险因素 ，是血脂异常的常见表现之一。高胆固醇血症以低密度脂蛋白胆固醇（LDL-C）或总胆固醇（TC）的升高为特点，有效降低LDL-C水平对管理血脂健康尤为关键，尤其对危险程度较高的患者而言。严格控制LDL-C水平，可显著减少ASCVD的发病及死亡危险。 据欧加隆新闻稿介绍，DYSIS-China研究显示，在已接受常规调脂治疗三个月（绝大部分为他汀单药治疗）的中国血脂异常患者中，二级预防LDL-C达标率仅有33.09%，其中极高危患者达标率更低，仅为26.86%。大部分患者需调整现有的降脂治疗方式以实现降脂达标。药物联用逐步成为中国降脂治疗的基本趋势和重要策略。依折麦布阿托伐他汀钙片是依折麦布与阿托伐他汀的固定复方制剂，在临床中，这两种药物成分均已广泛用于降低低LDL-C水平。其中，阿托伐他汀通过抑制胆固醇合成途径的限速酶——羟甲基戊二酰辅酶 A 还原酶，从而减少肝脏胆固醇的合成。依折麦布通过选择性抑制小肠胆固醇转运蛋白，减少肠道内胆固醇吸收，降低肝脏胆固醇储量。研究表明，阿托伐他汀与依折麦布两种药物分别影响胆固醇的合成和吸收，可产生良好协同作用。依折麦布阿托伐他汀钙片于2013年获得美国FDA批准，用于治疗原发性或混合性高脂血症患者LDL-C升高，以及用于降低纯合子家族性高胆固醇血症（FH）患者的胆固醇水平。8.安斯泰来AR抑制剂恩扎卢胺新适应症在中国申报上市9月19日，安斯泰来（Astellas）宣布，中国国家药监局药品审评中心（CDE）已受理恩扎卢胺软胶囊（商品名为安可坦）的新适应症上市申请，用于治疗转移性激素敏感性前列腺癌（mHSPC）。公开资料显示，恩扎卢胺是一款特异性雄激素受体（AR）抑制剂，此前已在中国获批治疗去势抵抗性前列腺癌。本次申请也是恩扎卢胺在中国晚期前列腺癌治疗领域获得受理的第三项申请。前列腺癌是男性泌尿生殖系统癌症中常见的肿瘤疾病。一旦前列腺癌扩散到前列腺以外的身体其他部位，如远处淋巴结、骨骼、肺部和肝脏，就被视为转移性癌症。如果男性患者对降低睾酮水平的药物或手术治疗仍有效果，则被认为对激素（或去势）敏感。转移性激素敏感性前列腺癌（mHSPC）男性患者开始接受雄激素剥夺疗法（ADT）治疗后的中位生存期约为3-4年。恩扎卢胺（enzalutamide）是一种雄激素受体信号抑制剂，它不但能够阻断雄激素与受体的结合，还能够抑制受体向细胞核内转移，以及雄激素受体与DNA的结合。因此它不仅仅是雄激素受体的拮抗剂，对雄激素信号通路也有抑制作用。2009年10月，Medivation（现为辉瑞[Pfizer]旗下公司）和安斯泰来签订商业协议，在美国对恩扎卢胺进行联合开发和商业化，安斯泰来负责全球范围内的生产和所有附加监管审批文件的提交，以及产品在美国以外地区的商业化。在中国，恩扎卢胺此前已获批用于治疗转移性去势抵抗性前列腺癌（mCRPC）和非转移性去势抵抗性前列腺癌（nmCRPC）患者。9.卒中预防药物显著优于标准疗法，Anthos 2期大型试验积极结果公布9月19日，Anthos Therapeutics宣布，在1287名具有中至高卒中风险房颤（AF）患者中开展的AZALEA-TIMI 71临床2期研究达到主要终点。与使用标准治疗药物的患者相比，使用其在研药品abelacimab患者的大出血和临床相关非大出血的复合终点显著降低，数据监测委员会建议终止该研究。此外，根据新闻稿，与直接口服抗凝血剂相比，abelacimab是首个显示显著降低大出血的凝血因子XI抑制剂。该试验的完整结果将在即将召开的科学大会上公布。心房颤动是最常见的心律失常类型，影响全世界约3350万人。随着人们预期寿命的增加，预计发病率在未来十年也将会随之增加，据预估，直至2030年，欧美地区将有约2400万人罹患此病。AF的特征是心脏上腔即心房的电活动混乱，导致心率不规则和高心率。AF与生活质量受损、住院率增加和卒中风险增加5倍相关。然而，40%-60%的房颤患者没有使用处方抗凝剂。这种抗凝血药物在卒中预防中的使用不足被认为是心血管患者面临的最大公共卫生问题之一。在一项医生调查中，避免患者服用口服抗凝剂的最大原因是与出血相关的事件。Abelacimab是一种新型、高选择性、全人源单克隆抗体，可靶向凝血因子XI并将之锁定在无活性状态，因此对凝血因子XI及其活化形式凝血因子XIa产生双重抑制。在《新英格兰医学杂志》上所发表的概念验证研究显示，与标准对照药物相比，abelacimab使患者减少约80%的静脉血栓栓塞（VTE）。Abelacimab曾获美国FDA授予快速通道资格，用于预防房颤患者卒中和全身性栓塞。10.Orchard基因疗法Libmeldy有望明年初获批，治疗这种致命疾病9月19日，Orchard Therapeutics宣布，美国FDA已接受其基因疗法Libmeldy（atidarsagene autotemcel）治疗异染性脑白质营养不良（MLD）的生物制品许可申请（BLA），并授予优先审评资格。FDA预计于2024年3月18日前完成审查。试验数据表明，施以该一次性基因疗法能够持续保留患者的运动功能和认知发育能力。MLD是一种罕见且危及生命的机体代谢系统遗传性疾病，根据现有文献估计发生率约为1/10万新生儿。MLD是由芳基硫酸酯酶-a（ARSA）基因突变引起的，导致硫酸盐在脑和身体其他区域蓄积，包括肝脏、胆囊、肾脏和/或脾脏。随着时间的推移，患者的神经系统会受损，导致其在运动、行为和认知上退化，并发生严重痉挛和癫痫发作等神经问题。MLD患者会逐渐丧失活动、说话、吞咽、进食和视物的能力。在婴儿晚期，发病后5年的死亡率估计为50%，10年的死亡率估计为44%。Libmeldy（又名OTL-200）使用慢病毒载体将编码芳基硫酸酯酶-A的ARSA转基因导入到患者自体CD34阳性造血干细胞和祖细胞中，该疗法已在欧盟获批用于治疗以ARSA基因双等位基因突变导致儿童ARSA酶活性降低为特征的MLD患者。Libmeldy是首个获批用于符合资格的早发性MLD患者的疗法。该BLA申请是基于39例早发性MLD儿科患者的数据，这些患者入组了两项前瞻性非随机临床研究（n=30）或在扩大使用框架下接受治疗（n=9），给予Libmeldy并与49例未接受治疗患者的自然史数据进行比较。在临床试验中，与疾病自然史相比，Libmeldy治疗可使大多数患者的运动功能和认知发育得以保留，随访时间长达12年（中位数6.76年）。11.全球首款！拜耳KEAP1激活剂启动I期临床9月18日，拜耳宣布其子公司Vividion Therapeutics开发的KEAP1激活剂VVD-130037（BAY 3605349）正式启动I期临床试验并完成了首例受试者给药。该试验旨在评估VVD-130037（口服，每日1次）在晚期实体瘤患者中的安全性、药代动力学和药效学以及初步疗效。VVD-130037是一款靶向Kelch样ECH相关蛋白1（KEAP1）的小分子激活剂。KEAP1是一种主要在细胞质中表达的E3泛素连接酶的亚基蛋白，负责调控下游核因子红系2相关因子2（NRF2）的水平。KEAP1与NRF2结合后，促进其泛素化并使其降解。研究表明，KEAP1-NRF2通路激活后，通过重组代谢来增强肿瘤细胞的增殖，抑制多种应激反应，促进免疫逃逸。Vividion于2021年8月被拜耳收购，是一家旨在利用新颖的发现技术针对高价值、不可成药靶点为毁灭性癌症和免疫性疾病开发精准疗法的生物制药公司。12.药物牧场ALPK1抑制剂完成1期试验首位受试者给药9月19日，药物牧场（Drug Farm）宣布，在健康志愿者中评估DF-003的1期临床试验的第一个受试者已经顺利完成给药。DF-003是通过药物牧场原创的IDInVivo+和MedChem5平台技术开发的ALPK1抑制剂小分子在研药物，已于今年7月在美国获批临床。ALPK1是心脏和肾脏病理中调节炎症通路的关键靶点。ALPK1的高活（Gain-of-function）突变也会导致一种罕见的遗传疾病ROSAH综合征，导致失明。因此，DF-003被认为有望治疗全球数亿患有心脏病和慢性肾脏疾病的患者，并为ROSAH综合征提供精准靶向药物。DF-003是一种高效的在研抑制剂，可抑制ALPK1和导致ROSAH患者患病的ALPK1 T237M驱动突变。该产品在心脏和肾脏动物疾病模型以及ROSAH转基因小鼠模型中展现出显著的临床前活性。此外，DF-003具有良好的类药特性，包括较低的脱靶风险和药物相互作用风险，以及符合人体每日一次给药的半衰期。13.新码生物新一代长效IL-2药物获批临床9月18日，浙江医药发布公告称，其下属子公司新码生物申报的1类新药注射用NCB003获批临床，拟开发适应症为晚期恶性实体瘤。NCB003是新码生物自主研发的新一代定点偶联长效人白介素-2药物，拟用于标准治疗失败的晚期恶性实体瘤，属于创新生物技术药物。公开资料显示，白介素-2（IL-2）是一种在维持T淋巴细胞和天然杀伤（NK）细胞的正常功能中起着重要作用的球状糖蛋白。IL-2主要由活化的T细胞生成，它能促进T细胞的增殖和分化，维持T细胞活性，刺激NK细胞的生成、增殖和活化，并诱导细胞毒性T淋巴细胞的生成，诱导和激活淋巴因子激活的杀伤细胞及肿瘤浸润淋巴细胞。基于白介素-2具有显著的增强免疫作用和很好的抗肿瘤临床应用潜力，目前已有多种重组人白介素-2上市产品应用于癌症治疗。但是白介素-2在临床上有半衰期短、副作用大的缺点，NCB003正是针对这些缺点而开发。据新码生物新闻稿介绍，临床前研究结果显示，NCB003对多种体内移植瘤有显著的抑制作用。该产品在血液循环中相对稳定，较白介素-2半衰期获得延长，且在起效剂量附近安全可耐受，有一定的安全窗口。14.云顶新耀注射用头孢吡肟/他尼硼巴坦拟被CDE纳入优先审评9月19日，CDE官网显示，云顶新耀注射用头孢吡肟/他尼硼巴坦拟纳入优先审评，用于治疗包括肾盂肾炎的成人复杂性尿路感染（cUTI）。注射用头孢吡肟/他尼硼巴坦是一种β-内酰胺/β-内酰胺酶抑制剂（BL/BLI）抗菌药物，云顶新耀与Venatorx正在开发其作为潜在治疗选择针对由抗菌药物耐药的革兰阴性菌引起的严重细菌感染，尤其是产超广谱β内酰胺酶（ESBL）肠杆菌目细菌、碳青霉烯耐药肠杆菌目细菌（CRE）和多重耐药铜绿假单胞菌（MDR-PA），其中包括碳青霉烯耐药铜绿假单胞菌（CRPA）。2018年9月25日，云顶新耀与Venatorx达成授权合作，将共同开发注射用头孢吡肟/他尼硼巴坦。云顶新耀拥有在大中华区、韩国和部分东南亚国家进行开发和商业化该药物的权益。FDA已于2023年8月受理注射用头孢吡肟/他尼硼巴坦新药上市申请(NDA) 并授予优先审评，预计将于2024年2月22日前做出审评决定。该新药上市申请是基于关键性III期临床研究CERTAIN-1的试验结果，该研究评估了注射用头孢吡肟/他尼硼巴坦与美罗培南在成人复杂性尿路感染（包括急性肾盂肾炎）中的疗效和安全性。在微生物学意向治疗（microITT）人群中，注射用头孢吡肟/他尼硼巴坦在疗效判定（TOC）访视（第19-23天）的微生物学和临床复合成功率的主要疗效终点上优于美罗培南。注射用头孢吡肟/他尼硼巴坦耐受性良好，未发现新的安全性信号。15.针对青少年湿疹，辉瑞JAK1抑制剂上市申请拟纳入优先审评9月19日，中国国家药品监督管理局药品审评中心（CDE）官网公示，辉瑞（Pfizer）口服JAK1抑制剂阿布昔替尼片（abrocitinib）上市申请拟纳入优先审评，拟定适应症为：用于对其他系统治疗（如激素或生物制剂）应答不佳或不适宜上述治疗的难治性、中重度特应性皮炎12岁及以上青少年患者。此前，该产品已在中国获批用于治疗难治性、中重度特应性皮炎成人患者。特应性皮炎（AD，又名湿疹）是一种以皮肤炎症和皮肤屏障缺陷为特征的慢性皮肤病，其特征为红/紫斑、瘙痒、硬结/丘疹、渗液/结痂。它也是常见的慢性复发性儿童皮肤病，在全球范围影响约10%的成人和约20%的儿童。许多中重度患者的病情控制不佳，需要额外的治疗方案来缓解症状。阿布昔替尼是一款口服JAK1抑制剂。JAK1抑制被认为可调节参与特应性皮炎病理生理学的多种细胞因子，包括白细胞介素IL-4、IL-13、IL-31、IL-22和胸腺基质淋巴细胞生成素（TSLP）。2022年4月，阿布昔替尼在中国获批上市，用于治疗对其他系统治疗（如激素或生物制剂）应答不佳或不适宜上述治疗的难治性、中重度特应性皮炎成人患者。根据CDE公示，此次阿布昔替尼拟纳入优先审评，针对适应症为12岁及以上青少年中重度特应性皮炎患者。阿布昔替尼治疗青少年特应性皮炎的疗效已在多项临床试验中得已证实。其中，包括随机、双盲、安慰剂对照的3期JADE TEEN研究，以及随机、双盲、安慰剂对照的3期JADE MONO-1研究和JADE MONO-2研究。JADE TEEN研究评估了阿布昔替尼在285例中度至重度特应性皮炎青少年（12至<18岁）患者中的疗效和安全性。16. 国产口服阿尔茨海默病新药III期研究成功，即将申报上市9月20日，通化金马药业发布公告，旗下1类新药琥珀八氢氨吖啶片用于治疗轻、中度阿尔茨海默病的III期临床试验已完成揭盲和主要数据的统计分析，达到主要终点。琥珀八氢氨吖啶片是一种新的乙酰胆碱酯酶抑制剂，具有双重胆碱酯酶抑制功能，可以同时抑制乙酰胆碱酯酶和丁酰胆碱酯酶。体外试验表明，琥珀八氢氨吖啶片对乙、丁两种胆碱酯酶的抑制能力分别是常规一线用药的数倍，故有更好的临床治疗效果，同时I期、II期临床也验证了其临床效果；并且，琥珀八氢氨吖啶片的安全性相对更可靠、更安全。本次III期临床试验结果显示，琥珀八氢氨吖啶片对AD评定量表认知部分（ADAS-cog）的改善具有明显的临床意义；在安全性上，治疗组不良事件及不良反应的发生率均低于两个对照组。与安慰剂组比较，结果具有显著的统计学意义（P<0.001）。新闻稿指出，琥珀八氢氨吖啶片III期临床试验揭盲后，将进入统计报告、临床研究总结报告及新药注册申请资料撰写阶段。阿尔茨海默病（AD）是一种以进行性认知障碍和记忆力损害为主的中枢神经系统退行性疾病，主要病理特征是大脑萎缩、脑组织内老年斑、脑血管沉淀物和神经原纤维缠结。根据 2020 年第七次全国人口普查，国内 60 岁及以上人口264018 766 人，占人口的18.70%。与 2010 年第六次全国人口普查相比，中国老龄化人口增长加快，而AD在老年人中患病率高。阿尔茨海默病发病率持续上升，其社会和经济负担正在放大，给中国城乡居民带来重大的医疗和社会问题。17.默沙东“first-in-class”疗法获FDA优先审评资格，治疗晚期癌症患者9月20日，默沙东（MSD）宣布，美国FDA已接受其“first-in-class”缺氧诱导因子-2α（HIF-2α）抑制剂Welireg（belzutifan）的补充新药申请（sNDA），并授予优先审评资格，用于晚期肾细胞癌（RCC）成人患者的治疗，这些患者接受免疫检查点和抗血管生成疗法后发生疾病进展。FDA预定在2024年1月17日以前完成审评。肾细胞癌是最常见的肾癌类型，10例肾癌诊断中约9例为肾细胞癌。肾细胞癌男性约为女性的2倍。大多数病例是在其他腹部疾病的影像学检查中偶然发现的。约15%的肾癌患者确诊时已处于晚期。Welireg是FDA加速批准的首个HIF-2α抑制剂，目前已在美国、英国、加拿大和其他几个国家和地区获批，基于2期LITESPARK-004试验的客观缓解率（ORR）和缓解持续时间（DOR）数据，用于治疗相关肾细胞癌、中枢神经系统血管母细胞瘤或胰腺神经内分泌肿瘤、不需要立即手术的von Hippel-Lindau（VHL）疾病成人患者。此次sNDA的申请主要是基于LITESPARK-005试验的数据，基于由独立数据监查委员会进行的预定中期分析显示，在在接受过PD-1/PD-L1检查点抑制剂和血管内皮生长因子酪氨酸激酶抑制剂（VEGF-TKI）治疗后发生疾病进展的晚期RCC患者中，与依维莫司（everolimus）相比，Welireg组患者的无进展生存期（PFS）有统计学显著并具临床意义的改善。该试验的关键次要终点客观缓解率（ORR）亦显示具统计学显著改善。18.创新微生物组疗法2a期试验达主要终点9月20日，MRM Health报告了其在研疗法MH002治疗轻中度溃疡性结肠炎（UC）2a期临床试验的积极结果。该试验达成安全性的主要终点，接受MH002治疗患者亦展现初步UC缓解的疗效。该试验完整数据分析预计于2023年年底公布，公司已将该疗法推进至2/3期试验。溃疡性结肠炎是一种慢性、特发性、免疫介导的炎症性肠病（IBD），可引起从直肠延伸至更近端结肠不同程度的持续性粘膜炎症。溃疡性结肠炎的标志性体征和症状包括直肠出血、腹痛、血性腹泻、里急后重（压迫感）、尿急和大便失禁。溃疡性结肠炎的病程因患者而异，在某些情况下可能会引起并发症（包括癌症和死亡）或导致患者需要进行手术。该病症状的严重程度和病程的不可预测性给患者带来了沉重的负担，甚至常常会致残。MH002是款微生物组联合疗法，旨在富集UC患者的肠道微生物组，从而解决造成疾病的根本原因。MH002-UC-201试验是一项在45名UC患者中开展的多中心、随机双盲、安慰剂对照的2a期试验，旨在评估8周的MH002治疗在患者中的安全性（主要终点）、初始疗效和机制，该试验并包含另外8周的扩展期。该试验初步分析结果如下：达到主要终点：安全且耐受性良好，MH002给药达16周时并无观察到相关不良反应。观察到临床相关的初始疗效，包括在第8周时，在中心评估的Mayo内窥镜检查严重程度评分上，MH002组患者显示高于安慰剂组17%的显著改善（p=0.05），并且从治疗2周开始，观察到患者在粪便稠度上的显著改善（p=0.006）。在机制水平上，与安慰剂（18%）相比，粪便钙卫蛋白（肠道炎症标志物）中位数降低42%，证明该疗法的抗炎作用。19.晚期癌症82%客观缓解率！Scancell癌症疫苗2期试验数据亮眼9月20日，Scancell公布其2期SCOPE试验第一阶段的积极数据，该试验检视其在研癌症疫苗SCIB1联合检查点抑制剂（CPIs）治疗晚期黑色素瘤的疗效与安全性。分析显示，11例患者的初始客观缓解率（ORR）达82%，优于试验预定疗效目标70%的ORR。根据新闻稿，在不可切除转移性黑色素瘤中，该疗法展现的ORR高于其他双检查点抑制剂联合疗法。SCIB1是一种脱氧核糖核酸（DNA）质粒疫苗，编码来自黑色素瘤抗原酪氨酸酶相关蛋白-2（TRP-2）和糖蛋白100（GP100）的两个CD8表位，加上来自GP100的两个CD4表位。SCOPE是一项在接受PD-1抑制剂Opdivo（nivolumab）联合靶向CTLA-4抗体Yervoy（ipilimumab）或PD-1抑制剂Keytruda（pembrolizumab）治疗的晚期不可切除黑色素瘤患者中开展的SCIB1开放标签、多中心、2期试验。本研究的目的是确定与单独使用检查点抑制剂相比，在标准治疗检查点抑制剂中添加SCIB1是否可以改善晚期黑色素瘤患者的客观缓解率。在SCOPE试验的第一阶段，患者通过无针装置接受SCIB1联合目前可用的有效疗法，即nivolumab和ipilimumab。SCOPE试验的第一个里程碑是达成15例患者中超过8例获得缓解，这表明SCIB1联合二联CPI治疗可能有意义地改善这些患者的治疗结局。分析显示，9名患者达客观缓解，相当于ORR为82%，且为观察到毒性增加。在该时间点，肿瘤体积减少31%-94%。有4例患者达到25周成像评估，2例患者达到37周评估，显示总肿瘤负荷分别降低69%-94%和87%-94%。与此相比，在现实世界环境中仅接受该CPI双药治疗患者报告的ORR为50%，无进展生存期为11.5个月。20.默沙东帕博利珠单抗新适应症申报上市，治疗新诊断宫颈癌9月20日，默沙东宣布，帕博利珠单抗（Keytruda，K药）的补充生物制品许可申请（sBLA）获FDA优先审评，适应症为联合同步放化疗治疗新诊断的高风险局部晚期宫颈癌患者。PDUFA日期为2024年1月20日。如果获批，K药将成为这类人群的首个免疫疗法。此次sBLA主要是基于III期KEYNOTE-A18研究的积极结果。该研究是一项随机、双盲、平行对照的III期临床试验，共纳入1060例未接受过任何治疗的高风险（伴淋巴结阳性IB2-IIB期或III-IVA期）局部晚期宫颈癌患者，旨在评估K药联合同步放化疗对比同步放化疗的有效性和安全性。研究的主要终点为无进展生存期（PFS）和总生存期（OS）。试验组患者需接受20次K药（前5次Q3W，后15次Q6W）治疗并接受同步放化疗，外加外照射放疗（external beam radiotherapy，EBRT），随后接受同步放化疗。对照组患者则接受安慰剂治疗并接受同步放化疗，外加EBRT，随后接受同步放化疗。结果显示，该研究达到了PFS的主要终点。此外，总生存期（OS）也有延长的趋势，不过数据尚未成熟。此前，K药在宫颈癌适应症上已获批①单药治疗接受化疗后疾病进展的PD-L1阳性复发性或转移性宫颈癌②联合贝伐珠单抗和铂类化疗治疗持续性、复发性或转移性PD-L1阳性宫颈癌。宫颈癌是全球女性第四大常见癌症，主要由高危型人乳头瘤病毒（HPV）持续感染引起。据估计，2023年美国约1.4万例宫颈癌新发病例和4000例死亡病例。2020年，中国宫颈癌新发病例约11万例，死亡病例约6万例。21.华东医药司美格鲁肽生物类似药3期完成首例入组9月20日，华东医药宣布，其全资子公司中美华东和重庆派金生物（简称“重庆派金”）共同开展的司美格鲁肽注射液生物类似药3期临床试验完成首例受试者入组和给药。这是一项多中心、随机、开放、平行对照的3期临床研究，主要目的是在二甲双胍治疗后血糖控制不佳的2型糖尿病患者中，论证试验药物司美格鲁肽注射液与原研药在治疗32周后血糖控制的等效性。司美格鲁肽是一种长效人胰高糖素样肽-1（GLP-1）类似物，与天然GLP-1的氨基酸序列具有94%的同源性，能起到GLP-1受体激动剂的作用。司美格鲁肽原研药由诺和诺德（Novo Nordisk）开发，已经在海外获批用于治疗2型糖尿病以及控制普通肥胖或超重，并在中国获批用于2型糖尿病治疗。公开资料显示，司美格鲁肽通过刺激胰岛素分泌、降低胰高血糖素分泌来降低血糖。该药降低血糖的机制还涉及轻微延迟餐后早期胃排空。同时，司美格鲁肽还可降低食欲、减少食物摄入量、诱导减肥，并且能显著降低2型糖尿病患者重大心血管事件风险。华东医药在研的司美格鲁肽注射液为一款生物类似药，是一种高效能、高选择性的GLP-1受体激动剂，拟用于成人2型糖尿病的临床治疗。2020年10月，中美华东与重庆派金签署产品合作开发协议，就司美格鲁肽注射液在全球范围内进行合作开发及商业化。重庆派金负责完成司美格鲁肽注射液的临床前研究工作，达到在中国申报IND的标准；中美华东负责该产品后续的全球开发、注册及商业化。据华东医药新闻稿介绍，已完成的1期临床试验已证明该公司的司美格鲁肽注射液与原研产品在健康人中的药代动力学具有相似性。22.亚虹医药光动力药械组合产品3期临床达终点，拟申报上市！9月20日，亚虹医药宣布，其用于非手术治疗宫颈高级别鳞状上皮内病变（HSIL）的光动力药械组合产品APL-1702的国际多中心3期临床试验达到主要研究终点，有望成为一款针对宫颈HSIL疗效确证的非手术类产品。该公司将于近期与监管部门沟通递交该产品的新药上市申请事宜。宫颈癌的主要诱因是HPV病毒持续感染导致的宫颈癌前病变，其中约20%的HSIL人群可能在10年内进展为浸润性宫颈癌。随着两癌筛查和宫颈细胞学检查的普及，越来越多的宫颈癌前病变患者在其癌变前阶段被检测出来，预计患者人数将持续增加。宫颈HSIL患者传统治疗方式为局部手术，手术易产生宫颈出血、感染、宫颈功能不全等不良反应。宫颈功能不全会引起早产、流产、剖宫产率增加等一系列生育问题。在宫颈癌前病变的治疗领域，目前还缺乏经3期临床试验确证有临床疗效的非手术类产品获批上市。APL-1702是集药物和器械为一体的光动力治疗产品，作为非创伤性的新疗法，治疗过程简单，易于操作，不影响患者日常生活，有望让HSIL患者免除手术治疗的痛苦和副作用，特别针对育龄期女性，能够减少因手术治疗对未来生育带来的不利影响。此次达到主要终点的研究是一项前瞻、随机、双盲、安慰剂对照的国际多中心3期临床试验，目的是评估APL-1702对宫颈高级别鳞状上皮内病变的疗效及安全性。该研究由中国医学科学院北京协和医院郎景和院士担任主要研究者，共计入组402例受试者。目前，该研究已达到主要疗效终点，安全性良好。有关该项临床试验的详细数据，后续将在相关学术会议及期刊上公布。23.信达 PD-1/IL-2 双特异性抗体融合蛋白获批新临床9 月 20 日，据 CDE 官网显示，信达生物递交的 IBI363 临床试验申请获默示许可，联用贝伐珠单抗或仑伐替尼或呋喹替尼或/和化疗用于晚期肿瘤（受理号：CXSL2300471）。IBI363 是由信达生物自主研发的潜在同类首创（First-in-Class）新药，有效成分为 PD-1/IL-2 双特异性抗体融合蛋白。白细胞介素 2（Interleukin-2，IL-2）是第一个被发现和鉴定在 T 细胞发育和扩增中起重要作用的细胞因子，早在 20 世纪 90 年代，阿地白介素（IL-2）即被美国 FDA 批准用于转移性肾细胞癌和转移性黑色素瘤的治疗，然而由于其选择性差、治疗窗窄、副反应大，未能广泛应用于临床。IL-2 作为一个双功能的细胞因子，既可以通过 IL-2 受体 αβγ 三聚体诱导激活 CD4+调节性 T 细胞（Regulatory T cell, Treg），维持机体免疫抑制，又可以通过 IL-2 受体 βγ 二聚体刺激 CD8+T 细胞和自然杀伤细胞，维持机体抗肿瘤作用。绝大多数开发者采取去除 IL-2 与 IL-2 受体 α 的结合的策略，来减少 IL-2 突变对 Treg 细胞刺激，从而降低免疫抑制并最大化 IL-2 的抗肿瘤效果。然而这些 IL-2 的突变体（not-α IL-2）在临床上表现却不尽人意。信达的双特异性抗体中IL-2 臂采用 α-biased 设计，在提高疗效的同时降低 IL-2 相关毒性， PD-1 结合臂可以实现对 PD-1 的阻断和 IL-2 的选择性递送。因此，IBI363 具有同时阻断 PD-1/PD-L1 通路和激活 IL-2 通路两项功能，可以更精确和有效地实现对肿瘤特异性 T 细胞的靶向和激活。IBI363 不仅在多种荷瘤药理学模型中展现出了良好抗肿瘤活性，在 PD-1 耐药和转移模型中也表现出了突出的抑瘤效力。同时，在临床前模型中，IBI363 安全性特征良好，整体安全性可控。24.同宜医药第二代双配体偶联药物获FDA孤儿药资格9月20日，同宜医药宣布，该公司自主研发的第二代双配体偶联药物CBP-1019已经获得美国FDA授予孤儿药资格，用于治疗胰腺癌。据同宜医药新闻稿介绍，CBP-1019已经于今年1月在美国获批临床，孤儿药资格将有助于CBP-1019未来在美国开展胰腺癌适应症的注册申报、临床开展及商业化进程。同宜医药成立于2016年，致力于双靶向XDC药物的研发及产业化。据同宜医药创始人、董事长兼首席执行官（CEO）黄保华博士在此前接受药明康德内容团队采访时介绍：“XDC是各种偶联药物的统称，抗体偶联药物（ADC）是XDC中的一种。同宜医药正在开发的Bi-XDC是一种新型的靶向偶联药物。在这类药物的设计中，可使用双配体将所需的药物有效载荷精准、有效地传递到特定细胞中。同时，由于将一个抗体换成了一对分子量小得多的配体组合，降低了对单个靶点的成药要求，使得Bi-XDC药物可选择的靶点也更多。此外，Bi-XDC分子量更小，因而进入细胞更快，半衰期更短，药效和安全性也更好。”本次获得孤儿药资格的CBP-1019是同宜医药Bi-XDC技术平台的第二代产品，通过双配体系统搭载喜树碱衍生物。在同宜医药开发的第一款Bi-XDC药物CBP-1008的基础上，CBP-1019进一步进行了创新和优化，保留、优化了双配体部分，并对连接子进行改造，使其具有更好的稳定性和更高的安全性。据悉，CBP-1019的临床应用目标是治疗转移或复发的相关靶点受体双表达的晚期恶性肿瘤患者，包括但不限于晚期胰腺癌、晚期肺癌、晚期结直肠癌、晚期卵巢癌、晚期子宫内膜癌以及晚期宫颈癌等。在临床前的药效学评价中，CBP-1019在PDX肿瘤模型中表现出明显的抑制肿瘤效果，并且与剂量呈正相关。此外，动物在接受CBP-1019治疗时几乎没有体重下降，显示出良好的安全性。25.北海康成引进的IBAT抑制剂氯马昔巴特口服溶液拟纳入优先审评9月21日，中国国家药监局药品审评中心（CDE）官网最新公示，北海康成申请的氯马昔巴特口服溶液拟纳入优先审评，用于治疗2月龄及以上进行性家族性肝内胆汁淤积症（PFIC）患者的胆汁淤积瘙痒症。此前，该产品已在中国获批用于治疗1岁及以上阿拉杰里综合征（ALGS）患者胆汁淤积性瘙痒。PFIC是一种可导致进行性肝病的罕见遗传性疾病，已在中国被纳入《第一批罕见病目录》。PFIC患者的肝脏分泌胆汁的能力较差，胆汁在肝内积聚会导致肝病，严重的会导致肝衰竭。该病的体征和症状通常始于婴儿期，患者会出现严重的瘙痒、黄疸、生长缓慢或无法生长，以及肝功能的逐渐丧失。目前已鉴定出6种类型的PFIC，均以胆汁流动受损和进展性肝病为特征。氯马昔巴特口服溶液（maralixibat）是一种几乎不被吸收的回肠胆汁酸转运蛋白（IBAT）抑制剂，可阻断胆汁酸肠肝回圈，降低肝内和血清中的胆汁酸水平，减少由此介导的肝脏损伤，缓解胆汁淤积瘙痒（极度瘙痒）。根据与Mirum公司的协议，北海康成拥有氯马昔巴特口服溶液在大中华区开发和商业化以及在特定条件下生产的独家授权，用于治疗包括胆道闭锁（BA）、阿拉杰里综合征（ALGS）和进行性家族性肝内胆汁淤积症（PFIC）在内的三种罕见肝病以及其他可选择的适应症。此前，氯马昔巴特口服溶液已在治疗PFIC的3期MARCH研究中取得了积极顶线数据。该研究评估了候选药在广泛亚型PFIC患者的疗效，共有93例年龄介于1-17岁的患者入组。结果显示，与接受安慰剂的患者相比，接受了氯马昔巴特口服溶液治疗的所有PFIC亚型的患者，主要与次要终点均获得了高度的统计学意义上的改善。其中主要终点为与基线时相比瘙痒严重程度的改善，而次要终点则是与基线相比的血清胆汁酸水平。26.重磅偏头痛新药！诺华依瑞奈尤单抗注射液在华获批上市9月21日，诺华的依瑞奈尤单抗（Erenumab）注射液在华获批上市，每月仅需1次，用于预防成人偏头痛。Erenumab是安进和诺华共同开发的一款通过阻断降钙素基因相关肽（CGRP）活性来预防偏头痛的全人源单克隆抗体。2018年5月，Erenumab获FDA批准上市，成为全球首个获批的针对CGRP受体的抗体药物；2018年7月在欧盟上市。根据公司财报，Erenumab在2022年的销售收入为6.32亿美元。2021年3月，诺华宣布DRAGON III期研究取得积极结果，达到主要终点。这是一项随机双盲、多中心、安慰剂对照的III期临床试验，旨在评估Erenumab预防性治疗成人慢性偏头痛的有效性和安全性。该研究共入组557例患者，以亚洲为中心、中国人群为主。结果表明，Erenumab 70mg组在12周双盲治疗期最后4周相比基线降低每月偏头痛天数（MMD）疗效终点（主要终点）上显著优于安慰剂组。此外，Erenumab 70mg组每月偏头痛天数相比基线减少50%以上的应答率显著高于安慰剂组。同时，Erenumab的安全耐受性特征与安慰剂组相似，未发现新的安全性问题。偏头痛是一种常见的慢性神经血管性疾病，其病情特征为反复发作、一侧或双侧搏动性剧烈头痛且多发生于侧偏头部，并伴有恶心、呕吐和对光、声和气味的敏感性，约1/3的患者在发病前可出现神经系统先兆症状。它被世界卫生组织定义为最致残的慢性疾病之一。中国偏头痛患病率为9.3%，约有超过1.3亿患者，是全球偏头痛患病人数最多的国家。通过规范的预防性治疗可有效提高急性期的治疗效果、降低发作频率和程度、减少对工作和生活的影响。27.过半患者抑郁症状消失！Relmada创新药物3期试验积极结果公布9月21日，Relmada Therapeutics宣布其在研药品REL-1017治疗重度抑郁症（MDD）患者的3期试验积极结果。分析显示，接受REL-1017初始治疗长达一年的患者在抑郁症状和相关功能障碍方面展现快速、有临床意义且持续的改善。抑郁症是一种常见的严重心理疾病，根据世界卫生组织（WHO）的统计，全球约有2.8亿患者，而且患者人数正在不断增加。抑郁症被WHO列为导致全球残疾的最主要原因之一，它不但影响患者的社会功能，严重情况下还会导致住院以及自杀。REL-1017是一种属于新化学实体（NCE）的NMDA受体通道阻断剂，它会优先靶向过度活化的通道，并同时维持生理性谷氨酸的神经递送，目前开发用于重度抑郁症的辅助治疗。这次所公布的REL-1017-310试验是一项长期、开放标签的3期试验，旨在评估MDD患者在接受每日一次REL-1017长达1年的疗效和安全性。总共入组了627例患者，包括从REL-1017安慰剂对照试验中入组的423例患者和既往未参加REL-1017试验的204例初治治疗患者。分析显示，分别有12.1%、30.1%、44.0%、47.8%与54.4%的患者在第7天、第1个月、第3个月、第6个月与第12个月几乎没有抑郁症状（临床缓解）。临床缓解定义为MADRS总分≤10。根据临床总体印象改善量表的评估，初治患者表现出有意义的改善，与MADRS疗效改善一致。第6个月时，REL-1017治疗使初治患者在Sheehan残疾量表（SDS）中所有三个独立领域的功能损害平均改善约50%，并进一步改善至第12个月。Sheehan残疾量表是一种广泛使用的患者评定量表，用于测量与MDD相关的三种个体领域的功能障碍：工作、社会生活和家庭生活。28.复宏汉霖抗PD-1单抗斯鲁利单抗在中国获批第4项适应症9月22日，中国国家药监局（NMPA）官网最新公示，复宏汉霖抗PD-1单抗斯鲁利单抗注射液的新适应症上市申请已获得批准。根据复宏汉霖早前发布的新闻稿，此次为该产品在中国获批的第4项适应症，具体为：联合化疗一线治疗局部晚期/复发或转移性食管鳞状细胞癌（ESCC）。斯鲁利单抗（HLX10）是一款重组人源化抗PD-1单抗注射液。这类产品通过与受体结合并阻断PD-1/L1通路，从而恢复机体的抗肿瘤免疫力。此前，斯鲁利单抗已在中国获批3项适应症，分别是：1）用于治疗经既往标准治疗失败的、不可切除或转移性微卫星高度不稳定（MSI-H）晚期实体瘤；2）联合化疗一线治疗局部晚期或转移性鳞状非小细胞肺癌；3联合化疗一线治疗广泛期小细胞肺癌（ES-SCLC）。公开资料显示，此次斯鲁利单抗在中国获批的新适应症为一线治疗食管鳞状细胞癌。该新适应症上市申请主要基于一项代号为ASTRUM-007的随机、双盲、多中心、3期临床研究。该研究由中国医学科学院肿瘤医院黄镜教授担任主要研究者，比较了斯鲁利单抗联合化疗或安慰剂联合化疗一线治疗局部晚期/复发或转移性ESCC的疗效和安全性。该研究结果已先后在2022年中国临床肿瘤学会（CSCO）年会和欧洲肿瘤内科学会亚洲年会（ESMO Asia）上进行了口头报告，并于2023年2月在《自然-医学》（Nature Medicine）上发表。该试验入组了551例既往未接受治疗、PD-L1阳性（综合阳性评分≥1）的晚期ESCC患者。数据显示，斯鲁利单抗联合化疗组的中位无进展生存期（PFS）和中位总生存期（OS）分别达到5.8个月和15.3个月，相比安慰剂联合化疗组均有明显改善（5.3个月和11.8个月）。研究中斯鲁利单抗联合化疗的安全性良好，未发现新的安全性信号。29.赛诺菲/再生元度普利尤单抗在中国获批新适应症，治疗成人结节性痒疹9月22日，中国国家药监局（NMPA）官网最新公示，由赛诺菲（Sanofi）和再生元（Regeneron）联合开发的度普利尤单抗注射液新适应症上市申请已获得批准。根据中国国家药监局药品审评中心（CDE）官网优先审评公示，该产品此次获批用于治疗成人结节性痒疹。值得注意的是，该药已于2022年9月获得FDA批准成为美国首个专门用于治疗结节性痒疹的药物。结节性痒疹是一种慢性2型炎症性皮肤病，会引起强烈的慢性瘙痒，并可能在全身出现皮肤增厚病变（结节）。该病是对生活质量所产生的负面影响最严重的炎症皮肤疾病之一，影响包括心理健康、日常生活活动和社会交往。目前患者缺乏有效疗法，通常使用高剂量外用类固醇减轻症状，但若长期使用，则存在安全性风险。度普利尤单抗（dupilumab，英文商品名：Dupixent）是一种全人源化单克隆抗体，可以抑制白细胞介素-4（IL-4）和白细胞介素-13（IL-13）蛋白的信号传导。研究表明，IL-4和IL-13是2型炎症的关键驱动因素，2型炎症在哮喘、慢性鼻窦炎伴鼻息肉病、特应性皮炎等炎症性疾病中发挥重要作用。度普利尤单抗能够通过IL-4和IL-13“双靶点”的创新作用机制阻断2型炎症通路，降低2型炎症的病理性反应，从机制上治疗2型炎症相关疾病。在海外，度普利尤单抗已在全球数十个国家和地区获批，用于治疗一种或多种适应症，包括针对不同年龄人群的特定特应性皮炎、哮喘、慢性鼻窦炎伴鼻息肉病（CRSwNP）、结节性痒疹和嗜酸性食管炎（EoE）等疾病。30.东阳光药糖尿病治疗产品精蛋白人胰岛素混合注射液获批上市9月22日，中国国家药品监督管理局（NMPA）官网最新公示，东阳光药以注册分类3.3类申报的精蛋白人胰岛素混合注射液（30R）上市申请已获得批准。公开资料显示，这是一种胰岛素制品，可用于治疗糖尿病。精蛋白人胰岛素注射液（30R）是一种预混胰岛素制品，由30%可溶性人胰岛素和70%精蛋白人胰岛素构成，适用于糖尿病的治疗。该产品通过皮下注射，具有低血糖发生率低、安全性良好的特点，可有效控制餐后血糖、空腹血糖和糖化血红蛋白（HbA1c）水平。根据中国药物临床试验登记与信息公示官网，东阳光药已完成一项1期临床研究，以诺和诺德（Novo Nordisk）在中国上市的精蛋白生物合成人胰岛素注射液（预混30R）（诺和灵30R）为对照药，评价单剂量皮下注射东阳光药的精蛋白重组人胰岛素注射液（预混30R）在健康受试者中的药代动力学性质，并评价试验药物和对照药品的生物等效性。该研究针对适应症为糖尿病。糖尿病是一种慢性疾病，当胰腺不再能够产生胰岛素或身体无法充分利用其产生的胰岛素时就会发生这种疾病。胰岛素被认为是降低高血糖的有效治疗方式，在饮食、锻炼或其他降糖药物无法达到足够的血糖控制的情况下，胰岛素适用于1型糖尿病和2型糖尿病患者的治疗。希望此次东阳光药精蛋白人胰岛素混合注射液（30R）获批，能够为广大糖尿病患者带来更多治疗选择。31.TROP2 ADC第2项III期研究达主要终点9月22日，第一三共和阿斯利康共同宣布Dato-DXd的第二项III期研究（TROPION-Breast01）在中期分析中达到无进展生存期（PFS）的主要终点。Dato-DXd（Datopotamab deruxtecan）是第一三共和阿斯利康合作开发的一款靶向TROP2的抗体药物偶联物（ADC）。Dato-DXd采用第一三共专有的DXd ADC技术设计，由与札幌医科大学合作开发的人源化抗TROP2 IgG1单克隆抗体组成，通过四肽可裂解连接子与多个拓扑异构酶I抑制剂有效载荷（一种exatecan衍生物）相连。TROPION-Breast01是一项全球性、随机、多中心、开放标签的III期试验，共纳入700例既往接受过内分泌治疗和至少一种系统治疗且无法手术或转移性HR阳性、HER2低表达或阴性（IHC 0、IHC 1+或IHC 2+/ISH-）乳腺癌患者，旨在评估评估Dato-DXd对比研究者选择的单药化疗（艾日布林、卡培他滨、长春瑞滨或吉西他滨）的安全性和有效性。结果显示，与对照组相比，Dato-DXd组患者的PFS延长时间具有统计学意义和临床意义。另一主要终点总生存期（OS）的数据尚不成熟，该试验将按计划继续进行以评估OS。此外，Dato-DXd的安全性与既往研究一致，没有发现新的安全信号。所有级别的间质性肺疾病发病率均较低。基于这些积极数据，第一三共和阿斯利康计划向全球监管机构提交Dato-DXd的上市申请。目前，全球仅有吉利德的Trodelvy（戈沙妥珠单抗）1款TROP2 ADC获批上市，适应症为尿路上皮癌、HR阳性乳腺癌和三阴性乳腺癌。32.迈威生物TMPRSS6抗体获FDA快速通道认定9月21日，迈威生物宣布美国FDA授予其铁稳态大分子调节药物9MW3011（MWTX-003/DISC-3405）快速通道认定 (FTD)，用于治疗真性红细胞增多症 (PV)。FDA 的快速通道认定 (FTD) 旨在加速用于治疗严重疾病的药物的开发与审查,进而加快这些药物的上市进程。获得FTD的治疗药物有望后续在符合相关标准条件时获得优先审查和加速批准。9MW3011是迈威生物位于美国的San Diego创新研发中心自主研发的抗TMPRSS6单克隆抗体，可通过与靶点特异性结合，上调肝细胞表达铁调素 (Hepcidin) 的水平，抑制铁的吸收和释放，降低血清铁水平，从而调节体内的铁稳态。适应症拟包括多种在全球不同地区被列为罕见病的疾病，如β-地中海贫血、真性红细胞增多症等与铁稳态相关的疾病。目前，相关适应症领域尚无成熟有效的大分子治疗药物。迈威生物已授予DISC MEDICINE除大中华区和东南亚以外所有区域内独家开发、生产和商业化以及以其他方式开发9MW3011的权利。迈威生物可获得合计最高达4.125亿美元的首付款及里程碑付款，以及产品上市后基于净销售额的特许权使用费。9MW3011已在中美获批开展临床试验，并于今年3月在国内完成首例受试者给药。33.全球首个ENPP1靶向药物进入III期临床9月21日，clinicaltrials.gove网站显示，Inozyme Pharma计划在9月22日启动一项III期临床试验（ENERGY 3），旨在评估INZ-701对比常规治疗在ENPP1（胞外核苷酸焦磷酸酶/磷酸二酯酶1）缺乏症儿童群体中的有效性和安全性。该研究拟纳入33例儿童ENPP1缺乏症患者，治疗周期为52周。常规治疗组患者将接受口服磷酸盐补充剂、骨化三醇或者其它维生素D3类似物。研究的主要终点为无机焦磷酸盐（PPi）的血浆浓度相比于基线的变化。胞外腺苷代谢系统在肿瘤、炎症、运动等多种生理病理过程中发挥着重要作用，ENPP1便是一种参与胞外腺苷代谢过程的重要成分。研究表明，ENPP1可以通过水解胞外核苷酸三磷酸盐（NTPs）产生PPi，进而调节骨骼和其它矿化组织的钙化过程。在动物研究中，缺乏ENPP1的小鼠由于胞外PPi水平降低而出现软骨和软组织的病理性钙化现象。医学研究表明，多种遗传性矿化、钙化相关疾病与ENPP1功能突变或缺失有关，例如常染色体隐性低磷佝偻病2型、婴儿期全身性动脉钙化（GACI）、钙化性冠状动脉病变、弹力纤维性假黄瘤等等。流行病学数据显示，ENPP1缺乏症的发病率约为1/64000个孕妇。大约50%的ENPP1缺乏症婴儿会在出生6个月内死亡。INZ-701是一种通过皮下注射给药的酶替代疗法（ERT），通过水解细胞外的ATP提高PPi和腺苷水平，以此模拟ENPP1的功能，从而起到治疗疾病的作用。在肿瘤领域也可以看到ENPP1的身影。ENPP1是胞外环磷酸鸟苷-腺苷合成酶（cGAMP）最主要的水解酶，可以将其水解为AMP和GMP，从而提高胞外腺苷水平。研究表明，腺苷水平过高会抑制免疫细胞的功能，而肿瘤中的腺苷水平常常远高于正常组织。合作动态1.百济神州pd1 在欧洲获批，并从诺华收回全球权益9月19日，百济神州发布晚间公告，百济神州瑞士和诺华签署《共同终止和释放协议》，共同终止授权协议。协议生效后，百济神州瑞士重新获得开发、生产和商业化替雷利珠单抗的全部全球权利，且无需支付特许使用费。诺华可以继续开展正在进行的临床试验，并且未来在获得公司同意后可以开展其他替雷利珠单抗联合用药试验。公司同意继续为诺华提供替雷利珠单抗的临床试验用药，以支持其临床试验的开展。此次终止不会影响百济神州瑞士前期已从诺华收到的6.5亿美元的现金首付款，亦不会对公司的财务状况和经营状况产生重大不利影响。另外，欧盟委员会已批准替雷利珠单抗作为单药用于治疗既往接受过含铂化疗的不可切除、局部晚期或转移性食管鳞状细胞癌（ESCC）的成人患者。本次欧盟委员会的批准遵循了欧洲药品管理局（EMA）人用药品委员会（CHMP）基于 RATIONALE 302 研究（NCT03430843）的积极意见。美国FDA已受理替雷利珠单抗的一项上市许可申请，用于一线治疗不可切除的局部晚期、复发或转移性的ESCC患者。此前，在 2021 年 1 月 11 日，百济神州与诺华签订了《合作与授权协议》，根据授权协议，百济授予诺华在美国、加拿大、墨西哥、欧盟成员国、英国、 挪威、瑞士、冰岛、列支敦士登、俄罗斯和日本开发、生产和商业化 Tislelizumab（替雷利珠单抗）的权利。根据授权协议，诺华负责在授权国家的注册申请，并有权在获批后开展商业化活动。2.苏州康宁杰瑞与远大生命科学集团就TFPI单克隆抗体KN057达成合作9月20日，苏州康宁杰瑞生物科技有限公司（简称“苏州康宁杰瑞”）与远大生命科学集团有限公司（简称“远大生命科学”）全资子公司四川远大蜀阳药业有限公司（简称“远大蜀阳”）在今日共同宣布，双方已就苏州康宁杰瑞自主研发的组织因子途径抑制物（TFPI）单克隆抗体KN057大中华区的权益许可签署合作协议。根据协议条款，苏州康宁杰瑞将继续负责KN057针对血友病A和血友病B的后续临床研究、上市注册申请及产品供应；远大蜀阳将独家负责KN057在大中华区的市场推广和商业化销售，并向苏州康宁杰瑞支付累计最高人民币5亿元的权益付款（包括首付款和里程碑款）及分级销售提成。KN057是苏州康宁杰瑞自主开发，具有自主知识产权的一种单克隆抗体，通过特异性靶向TFPI，中和TFPI对FXa以及TF/FVIIa复合物的抑制作用，维持凝血酶水平，达到预防出血的作用，有望对伴或不伴抑制物的A型和B型血友病患者均发挥疗效。KN057具有半衰期长、可皮下注射等特点，有利于提高血友病患者长期预防治疗的依从性和有效性，从而改善患者生活质量。目前，KN057针对血友病的II期临床研究已基本完成。3.超10亿美元！罗氏与PeptiDream再度牵手，合作开发肽-放射性偶联药物9月20日，PeptiDream宣布与罗氏旗下基因泰克达成一项新的多靶点合作和许可协议，旨在发现和开发新型大环肽-放射性同位素（肽-RI）偶联药物。根据协议，PeptiDream将使用其专有的肽发现平台系统（PDPS）技术来发现、优化和开发大环肽候选物，用于开发针对基因泰克感兴趣靶点的肽-RI偶联药物。PeptiDream将领导早期临床前开发，然后将合作产生的肽-RI偶联产品过渡给基因泰克进行进一步开发和商业化。PeptiDream将保留在日本开发和商业化此类肽-RI偶联产品的权利。根据协议条款，PeptiDream将从基因泰克获得4000万美元（59亿日元，1美元=147.7日元）的预付款，并有资格根据特定开发、监管和商业里程碑的实现获得潜在高达10亿美元（1477亿日元）的付款。此外，PeptiDream有资格获得合作产生的任何此类产品净销售额（除日本外）的分级版税。新的合作和许可协议建立在两家公司长期合作关系的基础上，双方于2015年12月签订了多靶标合作和许可协议，随后基因泰克于2016年获得了PeptiDream的PDPS技术授权，并于2018年扩大了双方的合作。4.德国默克达成逾12亿美元合作，针对这三个领域加速开发药物9月21日，德国默克（Merck KGaA）与人工智能（AI）公司BenevolentAI和Exscientia分别达成两项独立的AI药物发现合作，并专注于肿瘤学、神经病学和免疫学中的三个靶点。BenevolentAI公司的药物发现平台可以适用于任何疾病，并且具有发现大量创新靶点的能力。在德国默克与BenevolentAI的合作中，将利用BenevolentAI的端到端AI平台技术，并与其跨学科药物发现专家团队合作来开发新型候选药物，最初集中于肿瘤学、神经病学和免疫学的三个靶点。BenevolentAI将利用其AI化学设计工具套件，结合其湿实验室设施，将小分子药物开发候选物递送至德国默克管线，以进行临床前和临床开发。根据协议，德国默克将向BenevolentAI支付高达5.94亿美元的款项，包括预付款以及在达成发现、开发和商业等里程碑款项。BenevolentAI于去年1月也与阿斯利康（AstraZeneca）达成合作。对其在2019年针对慢性肾病和特发性肺纤维化创新疗法开发的合作上进一步扩展，将系统性红斑狼疮和心力衰竭添加到研发合作中。而德国默克与Exscientia的新合作亦集中在跨肿瘤学、神经炎症和免疫学的新型小分子候选药物的发现上，并亦专注于3个潜在的靶点。此外，这次合作亦使得德国默克和Exscientia能够在肿瘤学、免疫学或其他双方达成一致协议的疾病领域上确定额外的靶标。Exscientia公司开发的端到端AI驱动精准医药平台，可以使用患者数据来优化和筛选更有可能在临床中产生积极影响的分子。该平台利用表型组学、新型生物物理学和深度学习生物数据来评估药物靶点和机制，然后通过数千个模型驱动的AI算法，将该信息转化为精准药物的设计。值得一提的是，Exscientia公司所开发的端到端AI驱动精准医药平台，在2022年获得有“医药界的诺贝尔奖”之称的盖伦奖，显示行业对其技术的高度认可。5.超1亿美元，云顶新耀引进一款自免新药9月21日，云顶新耀宣布与Kezar Life Sciences签订合作与授权协议，将在大中华区和其他亚洲市场开发和商业化后者免疫蛋白酶体抑制剂zetomipzomib，这项合作涉及金额超1亿美元。昨日云顶新耀还宣布，其在研抗生素组合产品注射用头孢吡肟/他尼硼巴坦获中国国家药品监督管理局药品审评中心（CDE）拟纳入优先审评，用于治疗包括肾盂肾炎的成人复杂性尿路感染（cUTI）。云顶新耀与Kezar Life Sciences签订合作与授权协议，以在大中华区、韩国和部分东南亚国家进行临床开发和商业化后者在研产品zetomipzomib。根据协议条款，Kezar公司有权获得700万美元的预付款，以及最高为1.255亿美元的临床和商业里程碑付款，并可从产品净销售额中获得个位数至低十位数百分比的分级特许使用费。Zetomipzomib是Kezar公司的首款临床阶段候选药物，为一款选择性免疫蛋白酶体抑制剂，拟开发用于治疗包括狼疮性肾炎（LN）在内的一系列自身免疫性疾病。临床前研究表明，在多种自身免疫性疾病的动物模型中，选择性免疫蛋白酶体抑制能产生广泛的抗炎反应，同时可避免免疫抑制作用。云顶新耀将与Kezar公司共同推进全球性、安慰剂对照、随机、双盲的2b期PALIZADE临床研究，以评估两种剂量水平的zetomipzomib在活动性狼疮性肾炎患者中的疗效和安全性。该试验主要疗效终点是第37周时达到完全肾脏缓解（CRR）的患者比例。该试验已于2023年年中启动，目标是入组279名患者。前期试验数据表明，zetomipzomib表现出良好的安全性和耐受性，同时患者在接受6个月zetomipzomib治疗后表现出具有临床意义的总体肾脏治疗效果。除了狼疮性肾炎之外，云顶新耀和Kezar还有机会在其他自身免疫性疾病如系统性红斑狼疮的临床试验和适应症方面进行合作，以继续开发zetomipzomib。6.盟科药业抗感染新药获FDA授予合格传染病产品和快速通道资格9月21日，盟科药业宣布美国FDA授予康替唑胺片和MRX-4（contezolid acefosamil）用于治疗中度至重度糖尿病足感染且不伴有骨髓炎的适应症合格传染病产品（QIDP）和快速通道资格。康替唑胺片和MRX-4为盟科药业研发的噁唑烷酮类抗生素，主要针对的是耐药革兰氏阳性菌感染。根据盟科药业新闻稿，当新药获得QIDP资格认定之后，便会被授予审评阶段的优先审评等激励政策。康替唑胺属于新一代噁唑烷酮抗菌药，已于2021年6月在中国获批用于治疗复杂性皮肤及软组织感染。该药抗菌谱可覆盖阳性球菌、阳性杆菌、分枝杆菌及类真菌，尤其是对耐药菌株具有高度抗菌活性。由于作用机制及结构的特殊性，康替唑胺更难产生耐药，与其他类型的抗菌药也不易发生交叉耐药。此外，该药口服制剂给药吸收后可快速分布到皮下组织，同时对其他组织的穿透性强，体内分布广，血液学毒性和药物-药物相互作用的风险较低。MRX-4是基于康替唑胺结构独特设计和开发的水溶性前药，具有新的分子结构，可在体内转化为康替唑胺发挥疗效。该产品在满足口服给药的基础上，增加静脉给药的方式，为不同临床应用场景提供更多用药选择。目前，注射用MRX-4序贯康替唑胺片治疗糖尿病足感染的全球3期临床试验正在进行中。早在2018年时，康替唑胺片和MRX-4针对急性细菌性皮肤和皮肤结构感染（ABSSSI）的适应症已经被FDA授予了QIDP资格和快速通道资格。本次获得快速通道资格和合格传染病产品，将为康替唑胺片和MRX-4在美国的上市获批带来更多便利，尽快为广大的糖尿病足感染患者带来更多的用药选择。7.创响生物与Aditum Bio合作成立新药研发公司9月22日，创响生物宣布与风险投资公司Aditum Bio合作，创建一家利用清除病理细胞的机理治疗自身免疫和炎症疾病的新药研发公司Celexor Bio（下简称Celexor）。Celexor公司基于创响生物靶向免疫球蛋白样转录物7（ILT7）的单克隆抗体IMG-018成立。根据协议条款，Celexor公司获得了IMG-018的全球开发、制造和商业化的独家权利，创响生物将获得首付款和最高可达2.87亿美元的开发和销售里程碑付款，以及未来产品的销售分成。此外，创响生物还将获得Celexor公司的部分股权。IMG-018将更名为CLXR-901，交易预计将于本月底完成。IMG-018（CLXR-901）产生于创响生物专有的QuadraTek技术平台，是一种靶向浆细胞样树突状细胞（pDC）表面ILT7的单克隆抗体，可与ILT7受体结合并招募效应细胞以清除pDC。通过抗体工程改造，IMG-018具有增强的细胞杀伤功能，可通过多种效应细胞来发挥清除pDC的功能。创响生物董事长兼首席执行官（CEO）王健博士表示，Aditum Bio公司由具有丰富药物开发经验的制药行业资深人士创立。他们很高兴与Aditum Bio公司达成合作，基于IMG-018成立Celexor公司，这也展示了创响生物在开发具有创新性和差异化的候选药物方面的能力。关于新药情报库由智慧芽生物医药团队于 2022 年初推出，凭借首创的“全球大数据AI实时挖掘+药学专家团队校验” 情报处理机制，新药情报库已建立全球范围内的实时数据更新体系，覆盖超过4.5万+个靶点，7.3万+种新药，36.2万+个机构，80万+个临床试验，6000万+篇精选文献以及1300万+份药物专利。智慧芽新药情报库致力于为生物医药行业全产业链提供全面、精准、实时且标准化的全生命周期数据服务；新药情报库能够满足用户在规划新药管线、设定公司战略方向、寻找新药研发机会、评估项目引进价值、选择投资标的、追踪竞品策略、开发新客户等方面的数据情报获取需求。版权声明本文内容均由智慧芽生物医药小编收集于公开网络平台，版权由智慧芽所有，未经智慧芽授权不得转载。已获授权的应在授权范围内使用，并注明来源，违反上述声明者，智慧芽将追究其相关法律责任。如您发现相关信息有任何版权侵扰或者信息错误，请及时联系我们进行删改处理。授权相关事宜请联系：phs@patsnap.com