VIKTORIA-2: A Randomized, Open-Label, Phase 3 Study of Fulvestrant and CDK4/6 Inhibitors With or Without Gedatolisib as First-Line Treatment in Patients With HR-Positive and HER2-Negative Advanced Breast Cancer

This is a Phase 3, open-label, randomized, clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant and CDK4/6 Inhibitors for the treatment of patients with locally advanced or metastatic HR+/HER2- advanced breast cancer.

开始日期2025-06-30

申办/合作机构

Celcuity, Inc.

NCT06962969

/ Not yet recruitingN/A

Real-world Database Study to Observe Safety and Effectiveness of Ibrance

The purpose of this real-world study is to look at breast cancer patients receiving Palbociclib using a large real-world database collected under real-world practice. This study also looks at the safety of Ibrance, including any side effects. Side effects are undesired effects of a medicine or other type of treatment.
This study will include the data of the following participants:
* Adult women (more than18 years of age) with at least one visit with a breast cancer
* Patients with locally advanced breast cancer or metastatic breast cancer with a staging classification of stage III, stage IV. Advanced cancer is a term that is often used to describe cancer that is unlikely to be cured. Metastatic cancer is the cancer which is spread from the place where it started to other places in the body.
* Patients with a laboratory test positive for hormone receptor and negative for HER2 before or up to 60 days after advanced/metastatic breast cancer diagnosis date.
* Patients who received at least one initial prescription of Ibrance following a diagnosis of advanced/metastatic breast cancer.
This study will look at the safety of palbociclib treatment by looking at the number and severity of the side effects.

开始日期2025-05-01

申办/合作机构

Pfizer Inc.

NCT06947811

/ Not yet recruiting临床1/2期IIT

A Multicenter, Open-Label, Single-Arm, Phase Ib/II Clinical Study of Almonertinib Combined With Palbociclib in the Treatment of Patients With KRAS Mutations-Positive Advanced Solid Tumors

The main purpose of this study is to evaluate the safety and tolerability of almonertinib combined with palbociclib in patients with advanced solid tumors harboring KRAS gene mutations, and to conduct a preliminary observation of its efficacy

开始日期2025-04-30

申办/合作机构

中山大学

100 项与哌柏西利相关的临床结果

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100 项与哌柏西利相关的转化医学

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100 项与哌柏西利相关的专利（医药）

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3,525

项与哌柏西利相关的文献（医药）

2025-09-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Rationally designed Pyrazolo[1,5-a]pyrimidines as dual inhibitors of CA IX/XII and CDK6: A novel approach for NSCLC treatment

Article

作者: Salem, Rofaida ; Ismail, Rania S M ; Giovannuzzi, Simone ; Ghabbour, Hazem A ; El-Refaie, Wessam M ; Elkelesh, Islam A ; Nocentini, Alessio ; Abdel-Aziz, Hatem A ; Supuran, Claudiu T ; Fares, Mohamed ; Almehizia, Abdulrahman A ; Elkotamy, Mahmoud S ; Naglah, Ahmed M ; Eldehna, Wagdy M

Developing novel anticancer agents that target critical pathways in non-small cell lung cancer (NSCLC) presents a considerable challenge. This study synthesized 16 pyrazolo[1,5-a]pyrimidine derivatives with zinc-binding groups through molecular hybridization to achieve dual-target inhibition of tumor-associated carbonic anhydrase (CA) isoforms IX/XII and cyclin-dependent kinase 6 (CDK6). In-vitro assays indicated that sulfonamide-bearing compounds displayed enhanced CA inhibition, with compounds 7d, 11b, and 11d presenting K_i values of 11.2, 18.4, and 19.7 nM for CA IX, while compounds 11a and 11c exhibited K_i values of 14.8 and 8.7 nM for CA XII. Cytotoxicity assays conducted on NSCLC cell lines A549 and NCI-H1734 demonstrated that compounds 7c, 7d, 7i, and 11d exhibited superior activity relative to Roscovitine in both cell lines. While these compounds demonstrated limited inhibition of cyclin-dependent kinase 4 (CDK4), 7d and 11d effectively inhibited CDK6, with IC₅₀ values of 0.054 and 0.069 μM, respectively, which are comparable to Palbociclib. Analyses of the cell cycle and apoptosis demonstrated a strong G1 arrest and a notable induction of apoptosis. Molecular docking confirmed essential binding interactions with CA IX/XII and CDK6, while in-silico ADMET predictions suggested favorable pharmacokinetics, despite potential toxicity concerns. Compounds 7d and 11d represent potential dual-target inhibitors for the treatment of NSCLC.

2025-08-01·BREAST

Nationwide real-world practice pattern and clinical data of palbociclib in HR (+), HER2 (−) metastatic breast cancer patients in Korea (KCSG BR21-15)

Article

作者: Kim, Jee Hung ; Kim, Hyun Seon ; Park, In Hae ; Kim, Ji-Yeon ; Koh, Sung Ae ; Lee, Dae-Won ; Kim, Han Jo ; Hong, Soojung ; Baek, Sun Kyung ; Kang, Myoung Joo ; Kim, Seul-Gi ; Kim, Min Hwan ; Won, Hye Sung ; Kim, Gun Min ; Shin, Kabsoo ; Koh, Su-Jin ; Lee, Jieun ; Shin, Seong Hoon ; Park, Yeon Hee ; Jung, Joo Young ; Lee, Kyoung Eun ; Kim, Ju Won ; Im, Seock-Ah ; Woo, In Sook ; Byun, Jae-Ho

BACKGROUND:

Cyclin-dependent kinase (CDK) 4/6 inhibitors have remarkably improved the survival outcome in hormone-receptor-positive (HR+)/human epidermal growth factor-2-negative (HER2-) metastatic breast cancer (mBC). Although PALOMA-2 has met its primary outcome, overall survival (OS) was relatively shorter compared to ribociclib and abemaciclib. In Korea, use of palbociclib + aromatase inhibitor (AI) + gonadotropin-releasing hormone agonist (GnRHa) in premenopausal women is limited, and bilateral salpingo-oophorectomy (BSO) is necessary before treatment. We analyzed the real-world clinical outcome and patient characteristics of letrozole + palbociclib in Korea.

METHODS:

Between August 2016 and December 2022, 1017 HR+/HER2-postmenopausal women treated with first-line letrozole + palbociclib were enrolled. Primary endpoints were real-world progression-free survival (rwPFS) in total population and survival differences according to menopausal status (natural or induced menopause via BSO).

RESULTS:

Patients' median age was 56 (range 27-92) years. Median rwPFS, real-world OS (rwOS) were 28.0 months (95 % confidence interval [CI] 25.5-32.1) and 61.8 months (95 % CI 57.7-70.5), with a median follow-up of 45.1 (IQR, 31.0-56.6) months. BSO group demonstrated similar median rwPFS compared to natural menopause group. Adjuvant tamoxifen ± GnRHa was most frequently prescribed (73.3 %). Primary endocrine resistant mBC patients showed inferior median rwPFS compared to secondary resistant mBC (14.6 vs. 27.1 months, p = 0.0063). Overall response rate was 47.5 %, with a disease control rate of 89.6 %.

CONCLUSION:

This is the largest country-based real-world study on palbociclib + letrozole in Asia. Palbociclib demonstrated median rwOS over 60 months, comparable to other pivotal trials.

2025-07-01·BREAST CANCER RESEARCH AND TREATMENT

Non-adherence of cyclin-dependent kinases 4 and 6 inhibitors reduces overall and progression-free survival in patients with hormone receptor–positive breast cancer

Article

作者: LaBorde, Krista ; Alfartosy, Shahad S ; Trivedi, Meghana V ; De La Torre, Rodrigo ; Abughosh, Susan ; Brown, Erika N ; Fatima, Bilqees ; Lau, Connie

PURPOSE:

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy improve survival in patients with hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer (BC). This retrospective study aimed to evaluate CDK4/6i adherence, factors associated with non-adherence, the impact of health-system specialty pharmacy on adherence, and effects of non-adherence on survival outcomes in HR + /HER2- BC patients.

METHODS:

Data was collected from Houston Methodist Hospital System (HM) from HR + /HER2- BC patients with medication fill history utilizing electronic medical records. CDK4/6i adherence was calculated using the mean possession ratio ≥ 80%. Multivariable logistic regression model and Kaplan-Meier analysis were utilized to evaluate factors associated with non-adherence and its impact on survival, respectively.

RESULTS:

A total of 121 patients were assessed and analyzed; 55% patients received abemaciclib, 40% were on palbociclib, and 4% were on ribociclib. More patients were on aromatase inhibitors and tamoxifen (79%) than fulvestrant (21%). Most of the patients were Caucasian (64%), non-Hispanic or Latino (84%), and postmenopausal (66%). Overall, 52 patients (43%) were non-adherent. Patients ≥ 65 years of age (OR: 0.304, [95% CI: 0.110-0.840], P-value: 0.022) and those of Hispanic or Latino ethnicity (OR: 0.291, [95% CI: 0.086-0.985], P-value: 0.047) were more likely to be non-adherent to CDK4/6i. Non-adherence to CDK4/6i was associated with worse overall survival and progression-free survival.

CONCLUSION:

43% patients were non-adherent to CDK4/6i. Older patients and those of Hispanic ethnicity were more likely to be non-adherent. Non-adherent patients had worse survival outcomes, highlighting the unmet need to implement interventions to improve CDK4/6i adherence in these patients.

1,089

项与哌柏西利相关的新闻（医药）

2025-05-29

·ioncology

全球品质中国证据丨胡夕春教授：高效低毒的新型CDK4/6i来罗西利获批上市，为HR+/HER2-乳腺癌患者提供更优选择

点击蓝字，关注我们编者按：CDK4/6抑制剂（CDK4/6i）做为HR+/HER2-晚期乳腺癌（HR+/HER2- MBC）中的标准治疗药物，为患者治疗带来了更多有效方案。探索更高效低毒的新型CDK4/6i，对提升患者长期生存质量至关重要。今日，NMPA正式批准原研进口的来罗西利用于HR+/HER2- MBC成人患者的一线（与芳香化酶抑制剂联用）及二线（与氟维司群联用）治疗，此举标志着我国HR+/HER2-乳腺癌治疗迈入新阶段。值此之际，肿瘤瞭望特邀LEONARDA-2首席研究者复旦大学附属肿瘤医院胡夕春教授，深度剖析来罗西利的循证医学证据与药物机制优势，共探其临床应用前景。01肿瘤瞭望：在LEONARDA-2研究中，来罗西利联合来曲唑方案针对HR+/HER2-局部晚期或转移性乳腺癌患者展现出了卓越的疗效。您能详细分享一下该研究的主要疗效数据吗？这些数据的公布对于中国HR+晚期乳腺癌患者的一线治疗有何重要意义？胡夕春教授：来罗西利是一种新型CDK4/6抑制剂，在临床中进行了一系列研究。第一个针对中国患者的III期临床研究是LEONARDA-1研究[1]，该研究纳入了既往接受内分泌治疗后疾病复发或进展的HR+/HER2-晚期或转移性乳腺癌患者，评估了来罗西利+氟维司群治疗的疗效和安全性。结果显示，相较于对照组（安慰剂+氟维司群），研究组（来罗西利+氟维司群）能够明显提高患者的治疗效果，延长患者的PFS[研究者评估的PFS：11.07个月vs 5.49个月，风险比（HR）0.451，95%CI: 0.311～0.656，P=0.000016）]。鉴于来罗西利在晚期二线治疗的中成功，我们发起了针对中国患者的多中心III期LEONARDA-2研究[2]，该研究入组了HR+/HER2-晚期或转移性乳腺癌患者，这些患者在晚期阶段既往未接受过系统治疗。将患者按1∶1的比例随机分配至来罗西利联合来曲唑组（研究组）或安慰剂联合来曲唑组（对照组）。主要研究终点是由研究者评估的PFS。次要终点包括由盲法独立中心审查（BICR）评估的PFS、客观缓解率（ORR）、总生存期（OS）和安全性等。结果显示，研究组无论在PFS方面，还是在有效率方面，都明显优于对照组。与对照组相比，研究组显著改善患者的PFS[中位数：未达到（NR） vs 16.56个月；HR：0.464，95% Cl: 0.293～0.733；P=0.0004]，疾病进展或死亡风险降低约54%。此外，研究者评估和独立评审委员会（IRC）评估的PFS都显示出一致获益。在ORR和CBR方面，来罗西利+来曲唑也显示出了较好的临床获益。结合来罗西利在晚期乳腺癌一线及二线治疗阶段的临床试验数据，我们观察到，该药物不仅在这两个治疗阶段均显著提升了治疗有效率，提高了患者的临床获益程度，更在延长患者PFS方面展现出了卓越效果。为中国晚期HR+/HER2-乳腺癌患者开辟了一条新的治疗路径，带来了新的治疗希望与选择。02肿瘤瞭望：来罗西利作为一种结构创新的新型CDK4/6抑制剂，其独特的分子结构在LEONARDA-2研究中发挥了哪些关键作用？这种结构创新如何提升了中国HR+晚期乳腺癌患者的疗效和安全性？胡夕春教授：当前，中国市场上已有哌柏西利、阿贝西利、瑞波西利及达尔西利这4款CDK4/6抑制剂获批上市。在新药研发领域，我们始终致力于探寻疗效更优、安全性更高的CDK4/6抑制剂，即所谓的“me better”乃至“me best”药物，而来罗西利的研发正是基于这一初衷，旨在为患者带来更为理想的治疗方案。来罗西利的分子结构中引入了三并环&螺环结构，这种结构创新提升了其对CDK4靶点的亲和力（高选择性），降低了与非靶标蛋白的结合概率，从而减少了脱靶效应。临床前动物研究提示，来罗西利具有高渗透性，且其在肿瘤组织的分布浓度远高于血浆浓度，在血浆浓度降到未检出水平时，肿瘤组织浓度仍较高[3]，表现出肿瘤组织高渗透，血液低蓄积的特性。所以我们同样能够观察到，其给患者带来的骨髓抑制相较于其他CDK4/6抑制剂更轻。基于来罗西利PK/PD特征，来罗西利具备“me better”的苗头。在LEONARDA-2研究中[2]，相较于对照组，研究组的PFS、ORR和CBR均有更多获益，其中HR为0.464（95% Cl: 0.293～0.733），在当前已上市CDK4/6i一线研究中HR值处于偏低水平，表明来罗西利的临床获益好[4-9]；且各亚组获益一致，其中内脏转移、多转移部位（≥3）亚组的HR值分别为0.420、0.399，均优于全人群，这也印证了来罗西利的高选择、高渗透的作用机制。在药物安全性方面，研究组的不良反应率较低，总体安全性较好。特别是4级中性粒细胞减少症的发生率较低（5.1%），胃肠道不良事件多为轻度，且无静脉血栓栓塞事件（VTE）发生；与对照组相比，来罗西利组不增加Q-T间期延长。在耐受性方面，因TEAEs导致停用来罗西利的情况罕见[1例患者（0.7%）]。综上，结构创新使得来罗西利在中国HR+晚期乳腺癌患者中能够更有效地抑制肿瘤生长，延长患者的PFS，并提高患者的生活质量。03肿瘤瞭望：随着来罗西利联合来曲唑方案在中国获批上市，您认为这一新方案将对HR+晚期乳腺癌患者的一线治疗产生哪些深远影响？您如何看待这一新方案在未来临床实践中的应用前景？胡夕春教授：HR+/HER2-乳腺癌约占所有乳腺癌的70%。尽管我国目前已有4种CDK4/6抑制剂可供患者选择，但这一患者群体仍存在未被满足的临床需求。例如，在使用CDK4/6抑制剂治疗时，患者可能面临中性粒细胞减少、静脉血栓、Q-T间期延长、肝毒性等不良反应，这些都是我们需要解决的问题。因此，临床上我们需要找到一种既有效、毒副反应又比较低的药物。而LEONARDA-2研究[2]和LEONARDA-1研究[1]的结果以及已报道的其他CDK4/6i相关研究显示[4-9]，来罗西利联合内分泌治疗在血液系统毒性、Q-T间期延长、静脉血栓等方面的安全性表现非常出色。在指南规范和共识中，无论对于晚期一线治疗还是二线治疗，CDK4/6抑制剂都是HR+/HER2-乳腺癌的标准治疗药物。来罗西利的获批上市，使我们的治疗选择更加丰富。来罗西利联合内分泌治疗作为更高效、安全的选择，为临床医生提供了更多方案。在考虑患者治疗方案时，来罗西利联合内分泌治疗是可以优先考虑的。当然，要真正确定哪一种CDK4/6抑制剂是“最优选择”（me best），我们需要发起头对头研究。如果目前没有这样的临床研究，我们也希望通过真实世界的数据来进一步证明来罗西利是一种高效、安全的CDK4/6抑制剂。参考文献：（滑动查看）1、Xu, Binghe et al. “Lerociclib plus fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial.” Nature communications vol. 16,1 716. 16 Jan. 2025, doi:10.1038/s41467-025-56096-22、Xichun Hu,et al. LEONARDA-2: Lerociclib plus letrozole versus placebo plus letrozole in HR+/HER2- advanced or metastatic breast cancer. 2024 ASCO abstract 10523、Bisi, John E et al. “Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors.” Oncotarget vol. 8,26 (2017): 42343-42358. doi:10.18632/oncotarget.162164、Finn, Richard S et al. “The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.” The Lancet. Oncology vol. 16,1 (2015): 25-35. doi:10.1016/S1470-2045(14)71159-35、Finn, Richard S et al. “Palbociclib and Letrozole in Advanced Breast Cancer.” The New England journal of medicine vol. 375,20 (2016): 1925-1936. doi:10.1056/NEJMoa16073036、Goetz, M P et al. “Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3.” Annals of oncology : official journal of the European Society for Medical Oncology vol. 35,8 (2024): 718-727. doi:10.1016/j.annonc.2024.04.0137、Hortobagyi, Gabriel N et al. “Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer.” The New England journal of medicine vol. 386,10 (2022): 942-950. doi:10.1056/NEJMoa21146638、Tripathy, Debu et al. “Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial.” The Lancet. Oncology vol. 19,7 (2018): 904-915. doi:10.1016/S1470-2045(18)30292-49、Zhang, Pin et al. “Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.” The Lancet. Oncology vol. 24,6 (2023): 646-657. doi:10.1016/S1470-2045(23)00172-9胡夕春教授复旦大学附属肿瘤医院博士研究生导师ESMO乳腺癌Faculty Member国际ABC 5-7 panelist中华医学会肿瘤分会肿瘤内科专家委员会副主任委员中国抗癌协会多原发和不明原发肿瘤专委会荣誉主委中国抗癌协会临床化疗专委会副主委中国抗癌协会分子靶向专委会副主委中国研究型医院学会乳腺专业委员会副主委上海市医师协会肿瘤分会副会长上海市抗癌协会常务理事上海抗癌协会肿瘤药物临床研究专业委员会主任委员上海抗癌协会癌症康复和姑息治疗委员会前任主任委员国家食品药品监督管理总局审评中心审评专家发表论著300多篇，包括Lancet Oncol和杂志等主编《肿瘤内科方案的药物不良反应及对策》和《肿瘤科常见诊疗问题问答-胡夕春医生查房实录》等主持十三五“重大新药创制”科技重大专项等获上海市领军人才、中国抗癌协会科技奖二等奖、全国妇幼健康科学技术奖一等奖和上海市医学科技进步奖一等奖等（来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床3期上市批准临床结果临床2期

2025-05-28

·EINPresswire

Olema Oncology Announces Palazestrant Dose Selection and Trial-in-Progress Poster at ASCO 2025 Annual Meeting

90 mg once-daily palazestrant dose selected for Part 2 of the Phase 3 OPERA-01 monotherapy trial and for the Phase 3 OPERA-02 combination trial with ribociclib OPERA-01 trial-in-progress poster to be presented on Monday, June 2 between 9:00am–12:00pm CT / 10:00am–1:00pm ET SAN FRANCISCO, May 28, 2025 (GLOBE NEWSWIRE) -- Olema Pharmaceuticals, Inc. (“Olema” or “Olema Oncology”, Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, today announced it has aligned with the U.S. Food and Drug Administration (FDA) to select 90 mg of palazestrant as the dose for Part 2 of the ongoing registrational Phase 3 OPERA-01 trial in second- and third-line estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) metastatic breast cancer. This update will be presented as part of the OPERA-01 trial-in-progress poster at the American Society of Clinical Oncology (ASCO) Annual Meeting taking place May 30-June 3 in Chicago, Illinois. The FDA also selected 90 mg of palazestrant in combination with the approved dose of CDK4/6 inhibitor ribociclib for the pivotal Phase 3 OPERA-02 trial in frontline ER+/HER2- metastatic breast cancer. “Metastatic breast cancer treatment continues to be challenged by resistance mechanisms resulting in a clear need for innovative new therapies. We believe the clinical results we have achieved to date for palazestrant across ESR1 mutant and wild-type ER+/HER2- tumors, both in the monotherapy and combination treatment settings, support palazestrant’s potential to have a significant positive impact on breast cancer patients,” said Naseem Zojwalla, M.D., Chief Medical Officer of Olema Oncology. “We remain steadfast in our commitment to these patients, and with 90 mg of palazestrant confirmed as the selected dose, we are focused on rapidly advancing our OPERA-01 and OPERA-02 pivotal trials with top-line data from OPERA-01 anticipated in 2026 and a potential commercial launch in 2027.” Poster Presentation Details Title: OPERA-01: A randomized, open-label, phase 3 study of palazestrant (OP-1250) monotherapy vs standard-of-care endocrine therapy for patients with ER+, HER2- advanced breast cancer after endocrine and CDK4/6 inhibitor therapy Abstract Number: TPS1131 Poster Number: 104b Poster Session: Breast Cancer – Metastatic Date/Time: June 2, 2025 from 9:00am–12:00pm CT / 10:00am–1:00pm ET Additional information can be found on the ASCO Annual Meeting website , including abstracts. A copy of the poster will be made available on the Publications page of Olema’s website in alignment with ASCO’s embargo policy. About Palazestrant (OP-1250) Palazestrant (OP-1250) is a novel, orally available small molecule with dual activity as both a complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD). It is currently being investigated in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. In clinical studies, palazestrant completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of metastatic ER+ breast cancer and has demonstrated anti-tumor efficacy along with attractive pharmacokinetics and exposure, favorable tolerability, central nervous system penetration, and combinability with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Palazestrant has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. It is being evaluated as a single agent in the ongoing pivotal Phase 3 clinical trial, OPERA-01. Learn more at www.opera01study.com . Palazestrant is also being evaluated in multiple Phase 1/2 trials in combination with ribociclib, palbociclib, alpelisib, and everolimus. It will also be evaluated in combination with ribociclib in the planned pivotal Phase 3 trial, OPERA-02. About Olema Oncology Olema Oncology is a clinical-stage biopharmaceutical company committed to transforming the standard of care and improving outcomes for patients living with breast cancer and beyond. Olema is advancing a pipeline of novel therapies by leveraging our deep understanding of endocrine-driven cancers, nuclear receptors, and mechanisms of acquired resistance. Our lead product candidate, palazestrant (OP-1250), is a proprietary, orally available complete estrogen receptor (ER) antagonist (CERAN) and a selective ER degrader (SERD), currently in a Phase 3 clinical trial called OPERA-01. In addition, Olema is developing OP-3136, a potent lysine acetyltransferase 6 (KAT6) inhibitor, now in a Phase 1 clinical trial. Olema is headquartered in San Francisco and has operations in Cambridge, Massachusetts. For more information, please visit www.olema.com . Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Words such as “anticipate,” “believe,” “could,” “expect,” “goal,” “may,” “potential,” “upcoming,” “will,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These statements include those related to the potential of palazestrant to have a significant positive impact on breast cancer patients, the timing for initiation, enrollment, and results of Olema’s clinical trials, the timing of a potential commercial launch for palazestrant, and the potential beneficial characteristics, safety, tolerability, efficacy, and therapeutic effects of palazestrant. Because such statements deal with future events and are based on Olema’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of Olema could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, those discussed in the section titled “Risk Factors” in Olema’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, and other filings and reports that Olema makes from time to time with the U.S. Securities and Exchange Commission. Except as required by law, Olema assumes no obligation to update these forward-looking statements, including in the event that actual results differ materially from those anticipated in the forward-looking statements. Media and Investor Relations Contact Courtney O’Konek Vice President, Corporate Communications Olema Oncology media@olema.com Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

临床3期ASCO会议快速通道临床1期

2025-05-27

·CPHI制药在线

新一波专利悬崖面前，制药巨头安危分析

关注并星标CPHI制药在线制药领域是一个花无百日红的场所，不仅是因为“江山代有才人出”，也因为“风流总被雨打风吹去”。一款曾经“一览众山小”的重磅药物，在专利到期之后面对的通常会是“故国不堪回首月明中”的落寞。药品专利，这个起初旨在维护制药公司利益的保护伞，在逐渐走向专利悬崖的后期，却成为这些公司如芒在背的威胁。专利悬崖对大型制药公司，尤其是对那些依赖几款超级重磅炸弹药物的制药公司构成非常严重的威胁。当这些药物的专利到期后，仿制药制造商迅速进入市场，推出价格远低于原研药的替代品。这将直接导致原研药销售额的骤降，并削弱了这些开发商的盈利能力。由于超级重磅炸弹药物通常占公司总收入的相当大部分，一旦失去专利保护，公司可能难以在短期内通过新药研发或收购来弥补收入缺口。因此专利悬崖不仅威胁到公司的财务稳定，还可能影响其研发投入和市场竞争力。放眼大时代，2026-2030 年，生物制药行业将进入动荡时期，众多超重磅药物将在这一时期失去美国市场独占权。几乎所有大型制药公司都将或多或少受到头顶的这把专利到期达摩克利斯之剑的影响，但受威胁程度疾徐不一。诺和诺德、赛诺菲、吉利德、礼来和拜耳可能是2030年前“受灾”程度最小的五家制药巨头（表1，图1-2）。根据 Evaluate Pharma 的数据和Scrip的分析，预计从2026年至2030年，这五家制药商因专利到期遭受的损失将不超过各自2025年美国市场预测收入的15% 。在诺和等五家制药公司“事大如天醉亦休”地置身其外的同时，感受“日长似岁”般煎熬的制药巨头将面临渡劫。这些公司可能会因 2026 年至 2030 年美国专利到期药物而损失50% 以上的收入，其中葛兰素史克、百时美施贵宝和默沙东将面临最大危局。葛兰素史克的 Tivicay（多替拉韦）和 Dovato（拉米夫定）、百时美施贵宝的 Eliquis（阿哌沙班）和 Opdivo（纳武利尤单抗）以及默沙东的药王 Keytruda（帕博利珠单抗）等超级重磅药物可能将在这个时间段面临仿制药或生物类似药的竞争。表1. 全球大型制药公司2026-2030年受专利悬崖影响数据（数据来源：Evaluate Pharma）图1. 2025年预计美国市场收入中遭受2026-2030年间市场独占权丧失威胁的比例。（数据来源：Evaluate Pharma)图2. 大型制药公司2025年预计收入中面临2026-2030年间市场独占权丧失威胁的绝对数额。（数据来源：Evaluate Pharma）A.安全榜1.诺和诺德（2% 风险）诺和诺德的支柱性产品无疑是其Semaglutide产品组合，尤其是Ozempic和Wegovy。虽然诺和诺德将在GLP-1市场遭遇礼来和众多后来者的严峻挑战，以及Medicare价格谈判的潜在影响，但从专利悬崖的角度来看，诺和面临的压力要比默沙东小得多。Semaglutide在美国市场的核心专利保护预计将延续到2031年，这将赋予诺和诺德宝贵的开发新产品的黄金时间，在享受semaglutide巨大红利的同时，将利润投入到新一代产品的开发中，例如GLP-1/胰淀素类似物联合疗法CagriSema。2.赛诺菲（9% 风险）赛诺菲CEO Paul Hudson在今年1月召开的摩根大通医疗保健大会的演讲中就曾信誓旦旦地表态，“就独占权丧失而言，赛诺菲是业内最低的”。赛诺菲的当家花魁Dupixent (dupilumab) 仍处在生命周期的黄金时代，被批准用于从牛皮癣到哮喘等多种炎症疾病，最近还获得了慢性阻塞性肺病 (COPD)的批准，进一步夯实了这款超重磅药物的盈利能力。Dupixent 的专利保护期将持续到 2030 年代初。其活性成分专利将于 2031 年到期，其他专利有效时间则更长。Evaluate Pharma 的数据显示，赛诺菲预计的2025 年美国收入中只有 9% 会因 2026 年至 2030 年期间的市场独占丧失而损失，但这些损失多数来自“帐中副将”，例如乙型血友病药物Alprolix（重组凝血因子IX-Fc融合蛋白）和慢性移植物抗宿主病药物Rezurock（belumosudil），预计它们将分别在 2028 年和 2029 年失去独占权。3.吉利德（9%风险）吉利德追求的目标之一是在其核心 HIV 业务之外成功实现更多多元化，这个志向是建立在其HIV 业务一直在实现增长的基础之上的。吉利德最畅销的联合疗法的专利目前还一眼望不到底，2033 年底之前可保无虞。Biktarvy 在 2024 年的销售额为 134 亿美元，占吉利德总收入的将近48%。吉利德表示，在Biktarvy收入曲线进入下行阶段之前，他们将有能力推出新一代长效HIV药物。吉利德2025 年美国收入中只有9%将遭受到2026-2030年市场独占权丧失的影响，包括2027 年到期的CD19 靶向CAR-T疗法，而考虑到 CAR-T 疗法制造的复杂性，Tecartus未必在市场独占期到来之后立即面临生物类似药的竞争。4.拜耳（风险 13%）处在多事之秋的拜耳，其重磅产品血液稀释剂 Xarelto（rivaroxaban）市场独占期在2024年4月已经到来，令拜耳更加感受到压力重重。但遭受亏损的拜耳有望在2027年实现业务增长。拜耳CEO Bill Anderson 认为，用于治疗与 2 型糖尿病相关的慢性肾病的盐皮质激素受体拮抗剂 Kerendia（finerenone）和前列腺癌药物 Nubeqa（darolutamide）等新药将有助于推动拜耳回春。此外，BridgeBio 的 acoramidis 在欧洲将由拜耳负责商业化（欧洲商品名Beyonttra），针对转甲状腺素蛋白淀粉样心肌病 (ATTR-CM)。拜耳的elinzanetant针对更年期相关的中度至重度血管舒缩症状的申请正在等待FDA的监管审批。5.礼来（风险 15%）礼来的旗舰产品Mounjaro和Zepbound相对于其直接竞争对手，诺和诺德的Ozempic和Wegovy更加年轻。其活性成分tirzepatide的专利至少要到2036年才到期，这位礼来长期盈利提供了关键保障。礼来公司在 2026-2030 年期间也将面临一些畅销药物的专利损失，包括预计在 2027 年失去市场独占的糖尿病重磅药物 Trulicity（dulaglutide），其2024 年为礼来创造了 52.5 亿美元的收入；以及在 2030 年失去专利保护的牛皮癣药物 Taltz（ixekizumab），其2024 年销售额达到36 亿美元。B.风险榜1.默沙东（78%）Keytruda，默沙东的这款支柱产品免疫检查点抑制剂肿瘤学产品2024年销售额高达295亿美元，而默沙东全年销售额为642亿美元。也就是说，Keytruda以一己之力贡献了默沙东全部销售额的46%，这是一个非常卓越的成就，但同样也包藏祸机，因为Keytruda在美国的关键专利将在2028年到期，Keytruda专利悬崖危机成为默沙东目前的头号挑战。随着 Keytruda、Sitagliptin/Metformin和 Letermovir 的专利即将到期，默沙东未来五年将面临严峻挑战。另一个主要收入来源 HPV 疫苗 Gardasil 9 因中国市场饱和而表现不佳，导致默沙东于 2024 年 2 月暂停发货以清理库存，在 2025 年可能会恢复增长。为了保持增长，默沙东抗体药物偶联物 (ADC) 方面投入了大量资金，包括与科伦生物科技和第一三共的合作。2.GSK（62%）葛兰素史克的dolutegravir一直是其HIV 药物组合的主要产品，是葛兰素史克四个最畅销的 HIV 品牌 Tivicay（13.5亿英镑）、Triumeq（13.3亿英镑）、Juluca（6.85亿英镑）和 Dovato （22.4亿英镑）中的成分。但其关键专利可能将于2027年到期。3.BMS (55%)百时美施贵宝的Eliquis (Apixaban) 和 Opdivo 正面临专利悬崖危机，2024 年这两款药物的营收为 234 亿美元，占公司总营收的近一半。Eliquis面临即将到来的仿制药竞争，Eliquis是BMS与辉瑞共同商业化的产品，是一种用于预防成人血栓的小分子药物，2012年获得FDA批准，2023年实现全球122亿美元的销售额。其专利已于2022年到期，但得益于补充保护证书（Supplementary Protection Certificate）的荫护，其保护期已延长到2026年。实际上，Eliquis仿制药已经获得了FDA的临时批准，但BMS与仿制药商已经达成和解，仿制药不会在2027年之前上市。作为回应，BMS 实施了积极的成本削减措施，包括 2024 年 4 月的 15 亿美元成本削减计划和 2025 年 2 月的额外 20 亿美元削减计划，包含削减产品线和裁员。BMS 还将重点转向神经科学，以 140 亿美元收购了 Karuna Therapeutics，并投资了精神分裂症药物 Cobenfy。C.2025-2031年间失去市场独占权的重要药物2025年• Entresto (sacubitril/valsartan，诺华，2015年获批，2024年全球销售额：78.2亿美元，下同)• Farxiga (Dapagliflozin，诺华，2014年获批，2型糖尿病，38.4亿美元)• Prolia (denosumab，安进，2010年获批，骨质疏松症，43.7亿美元)• Xgeva (denosumab，安进，2010年获批，肿瘤，22.3亿美元) 2026年• Eliquis (apixaban，BMS/辉瑞，2012年获批，血栓，122亿美元)• Revlimid (lenalidomide，BMS，2005年获批，骨髓增生异常综合征、多发性骨髓瘤、淋巴瘤、滤泡性淋巴瘤等，57.7亿美元) 2027年• Trulicity (dulaglutide，礼来，2014年获批，2型糖尿病，52.5亿美元)• Ocrevus (ocrelizumab ，罗氏，2017年获批，多发性硬化症，67亿美元)• Ibrance (Palbociclib，辉瑞，2015年获批，乳腺癌，43.7亿美元)• Xtandi (enzalutamide，安斯泰来/辉瑞，2012年获批，前列腺癌，63亿美元)• Imbruvica (ibrutinib，艾伯维/强生，2013年获批，慢性淋巴细胞白血病等，49亿美元)• Dolutegravir药物组合 (GSK，2013年获批，HIV，56亿英镑) 2028年• Keytruda (pembrolizumab，默沙东，2014年获批，肿瘤，295亿美元)• Opdivo (nivolumab，BMS，2014年获批，肿瘤，93亿美元)• Gardasil 9 (human papillomavirus 9-valent vaccine ，2014年获批，默沙东，86亿美元) 2029年• Darzalex (daratumumab，强生/Genmab，2015年获批，多发性骨髓瘤，117亿美元)• Cosentyx (secukinumab，诺华，2015年获批，斑块性银屑病等，61.4亿美元)• Enbrel (etanercept，安进，1998年获批，类风湿性关节炎等，33.2亿美元) 2031年• Dupixent (dupilumab，赛诺菲/再生元，2017年获批，特应性皮炎、哮喘、慢性阻塞性肺病等，131亿欧元)Ref. 1、Merck Announces Fourth-Quarter and Full-Year 2024 Financial Results. Merck Press Release. 04. 02. 2025. 2、Merrill, J. et al. Five Companies Heading Toward 2030 With Wind At Their Back. Scrip. 26. 02. 2025. 3、2024 Financial report of various pharmaceuticals. 4、Pharma patent cliff. LinkedIn: Joanna-sadowska-phdEND【企业推荐】智药研习社直播预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

专利到期并购生物类似药

100 项与哌柏西利相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10372	哌柏西利	L01XE33	DB09073

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
复发性乳腺癌	日本	Pfizer Japan, Inc.	2017-09-27
HR阳性/HER2阴性乳腺癌	美国	Pfizer Inc.	2016-02-19
ER阳性/HER2阴性乳腺癌	美国	Pfizer Inc.	2015-02-03

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
HPV相关鳞状细胞癌	临床3期	美国	Pfizer Inc.	2022-04-06
头颈部鳞状细胞癌	临床3期	美国	Pfizer Inc.	2022-04-06
转移性头颈部鳞状细胞癌	临床3期	美国	Pfizer Inc.	2022-04-06
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	奥地利	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	法国	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	匈牙利	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	意大利	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	西班牙	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	瑞士	Pfizer Inc.	2019-08-27
HER2 阴性乳腺癌	临床3期	美国	Pfizer Inc.	2019-07-16

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05361655 (Pubmed \| Breast)	N/A	转移性乳腺癌一线	1,302	Palbociclib dose adjustments	衊衊襯廠鹽鏇醖遞鏇窪(醖獵鏇製淵憲淵糧鹽艱) = 網鹽襯顧願夢衊獵鹹願鹹艱蓋醖願淵鏇膚餘齋 (淵艱顧築壓願憲糧選餘 ) 更多	积极	2025-06-01
				No palbociclib dose adjustments	衊衊襯廠鹽鏇醖遞鏇窪(醖獵鏇製淵憲淵糧鹽艱) = 艱觸夢築廠鬱鹹齋鹽衊鹹艱蓋醖願淵鏇膚餘齋 (淵艱顧築壓願憲糧選餘 ) 更多
NCT03530696 (ESMO_BC 12025 \| ESMO_BC 22025) 人工标引	临床2期	HER2阳性乳腺癌 HER2 Positive	52	T-DM1	範網膚獵鬱餘襯醖襯廠(齋鑰獵醖壓繭衊餘廠願) = 齋鑰願製鏇衊築網鏇襯鏇遞餘鹽艱遞顧蓋觸艱 (繭鹽膚鏇齋繭獵壓顧積 ) 更多	积极	2025-05-16
				T-DM1 + Palbociclib	範網膚獵鬱餘襯醖襯廠(齋鑰獵醖壓繭衊餘廠願) = 膚鹹範衊憲鏇餘壓壓鏇鏇遞餘鹽艱遞顧蓋觸艱 (繭鹽膚鏇齋繭獵壓顧積 ) 更多
ESMO_BC2025	N/A	转移性乳腺癌一线	974	Palbociclib + Aromatase Inhibitor	願鹽艱膚壓構簾鑰願範(糧觸膚醖衊構餘憲簾糧) = 願鑰繭構簾齋醖顧鹽淵蓋範願廠繭鹽簾餘憲製 (鬱鬱網醖鑰觸顧鏇壓鬱, 56.2 ~ 79.6) 更多	积极	2025-05-14
				Aromatase Inhibitor alone	願鹽艱膚壓構簾鑰願範(糧觸膚醖衊構餘憲簾糧) = 窪簾壓糧獵鑰獵糧窪夢蓋範願廠繭鹽簾餘憲製 (鬱鬱網醖鑰觸顧鏇壓鬱, 44.8 ~ 65.1) 更多
ESMO_BC2025	N/A	一线	320	Palbociclib + Letrozole	淵鏇餘製膚願觸觸鬱鑰(膚壓鬱觸廠夢艱鬱鏇遞) = 鏇觸網築選製窪繭顧網鬱壓齋蓋蓋獵鏇獵選醖 (膚鏇衊糧鹹齋簾遞齋衊 )	积极	2025-05-14
				Palbociclib + Fulvestrant	淵鏇餘製膚願觸觸鬱鑰(膚壓鬱觸廠夢艱鬱鏇遞) = 鬱鬱網網壓艱製簾醖觸鬱壓齋蓋蓋獵鏇獵選醖 (膚鏇衊糧鹹齋簾遞齋衊 )
ESMO_BC2025	N/A	HER2阳性转移性乳腺癌	105	Palbociclib 125mg	糧膚繭積築顧廠襯鹹繭(鏇鬱憲糧鬱構鬱艱築獵) = 觸網觸獵衊積壓衊願構壓蓋憲獵餘願餘觸鹽選 (淵膚獵齋鑰遞範簾鬱鹽 ) 更多	积极	2025-05-14
NCT06086340 (Pubmed \| Cancer Med)	N/A	转移性乳腺癌 \| HR阳性/HER2阴性乳腺癌 HR+ \| HER2-	779	Palbociclib + Aromatase Inhibitor	遞蓋選衊鏇艱範憲齋積(艱艱獵淵築襯網壓醖鏇) = 蓋鏇繭鹽鬱壓糧積廠繭築齋鹹鹹鹽醖鬱願製構 (遞醖遞衊鹽鹹範蓋範淵 )	积极	2025-04-01
				Aromatase Inhibitor Alone	遞蓋選衊鏇艱範憲齋積(艱艱獵淵築襯網壓醖鏇) = 範鏇觸蓋繭壓淵壓範艱築齋鹹鹹鹽醖鬱願製構 (遞醖遞衊鹽鹹範蓋範淵 )
NCT01864746 (PENELOPE-B, Pubmed \| JCO Precis Oncol)	临床3期	新辅助 BRCA1/2	445	Palbociclib + Endocrine Therapy	積願憲蓋膚膚衊製壓蓋(齋襯鑰鹽壓艱顧築壓顧) = 築壓製積餘窪鹽廠積積艱構窪觸齋壓簾糧鬱鏇 (憲襯壓製淵淵觸網網壓 ) 更多	不佳	2025-04-01
				Placebo + Endocrine Therapy	積願憲蓋膚膚衊製壓蓋(齋襯鑰鹽壓艱顧築壓顧) = 願夢壓壓膚簾糧顧選蓋艱構窪觸齋壓簾糧鬱鏇 (憲襯壓製淵淵觸網網壓 ) 更多
NCT04494958 (PALBOBIN, CTgov)	临床1/2期	晚期三阴性乳腺癌	24	Palbociclib+Binimetinib	膚夢夢網艱積廠獵憲齋 = 齋築觸夢觸壓淵鑰襯鏇鬱鏇鬱衊壓餘鏇憲襯築 (鏇網遞繭鏇顧選構鹹夢, 網襯膚積鏇鑰願簾選鹽 ~ 鬱顧壓齋蓋鑰蓋顧願襯) 更多	-	2025-03-24
NCT03774472 (CTgov)	临床1/2期	ER阳性/HER2阴性乳腺癌 \| 转移性乳腺癌	15	HCQ (HCQ at 400 mg)	襯願獵糧繭鹽糧窪遞觸 = 顧獵艱艱積顧簾憲鬱憲壓蓋願憲鑰襯醖鹹願鑰 (衊鏇選衊顧壓觸襯繭膚, 齋糧淵襯觸顧範廠網築 ~ 鹽餘艱網製鹽夢憲餘膚) 更多	-	2025-02-17
				HCQ (HCQ at 600 mg)	襯願獵糧繭鹽糧窪遞觸 = 壓鏇壓夢艱糧鑰獵蓋繭壓蓋願憲鑰襯醖鹹願鑰 (衊鏇選衊顧壓觸襯繭膚, 襯製築窪醖鹽簾製獵餘 ~ 觸遞淵顧齋鹹衊製築淵) 更多
Pubmed \| Future Oncol	N/A	转移性乳腺癌	-	Palbociclib-fulvestrant	襯壓遞遞窪願蓋構衊艱(製憲餘觸鹽襯夢鹹願築) = 淵鹽繭鏇鬱廠獵構顧範簾鬱網繭網鬱窪願鹽築 (積衊繭襯廠艱觸願獵齋, 15.2 ~ 23.6)	-	2025-01-02