A PHASE 1, OPEN-LABEL, SINGLE DOSE STUDY TO INVESTIGATE THE PHARMACOKINETICS, PHARMACODYNAMICS, SAFETY, AND TOLERABILITY OF PONSEGROMAB ADMINISTERED SUBCUTANEOUSLY IN HEALTHY ADULT CHINESE PARTICIPANTS

The purpose of this clinical trial is to learn about the safety of the study medicine (ponsegromab) and how it undergoes change and elimination in healthy Chinese adults. This study is seeking male and female Chinese participants who are very healthy as confirmed after some medical tests.
All participants in this study will receive Ponsegromab only once:
* for half of the participants, ponsegromab will be given as a shot in the front of the thigh, abdomen, or outer area of the upper arm at the study clinic.
* for another half of the participants, ponsegromab will be given as four shots in the front of the thigh, abdomen, or outer area of the upper arm at the study clinic.
We will measure the amount of the study medicine in the blood of the participants after giving the shots. Later we will examine experiences of people receiving the study medicine. This will help us understand how the medicine is changed and eliminated from your body and to decide if the study medicine is safe. Participants will take part in this study for 22 weeks. During this time, they will stay at the study clinic for the first 8 days and will visit the study clinic about 8 times.

开始日期2023-01-18

申办/合作机构

Pfizer Inc.

100 项与 Ponsegromab 相关的临床结果

登录后查看更多信息

100 项与 Ponsegromab 相关的转化医学

登录后查看更多信息

100 项与 Ponsegromab 相关的专利（医药）

登录后查看更多信息

项与 Ponsegromab 相关的文献（医药）

2025-01-01·CANCER

Potential new treatment for cancer‐related cachexia

作者: Nierengarten, Mary Beth

This news section offers Cancer readers timely information on events, public policy analysis, topical issues, and personalities. In this issue, patients with cancer‐related cachexia who were treated with ponsegromab had a significant increase in weight gain from the baseline in comparison with patients treated with a placebo. Also, a new first‐line treatment improves progression‐free survival for select men with bone mCRPC, and the addition of an immune checkpoint inhibitor reduces the risk of disease progression for select patients with anal cancer.

2024-12-19·NEW ENGLAND JOURNAL OF MEDICINE

Ponsegromab for the Treatment of Cancer Cachexia

Article

作者: Karahanoglu, Isik ; Fallon, Marie ; Takayama, Koichi ; Groarke, John D. ; Crawford, Jeffrey ; Dunne, Richard F. ; Harrington, Magdalena A. ; Roeland, Eric J. ; Asmis, Timothy ; Hendifar, Andrew E. ; Northcott, Carrie A. ; Collins, Susie M. ; Saxena, Aditi R. ; Lubaczewski, Shannon ; Rossulek, Michelle ; Qiu, Ruolun ; Naito, Tateaki

BACKGROUND:

Cachexia is a common complication of cancer and is associated with an increased risk of death. The level of growth differentiation factor 15 (GDF-15), a circulating cytokine, is elevated in cancer cachexia. In a small, open-label, phase 1b study involving patients with cancer cachexia, ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed serum GDF-15 levels.

METHODS:

In this phase 2, randomized, double-blind, 12-week trial, we assigned patients with cancer cachexia and an elevated serum GDF-15 level (≥1500 pg per milliliter) in a 1:1:1:1 ratio to receive ponsegromab at a dose of 100 mg, 200 mg, or 400 mg or to receive placebo, administered subcutaneously every 4 weeks for three doses. The primary end point was the change from baseline in body weight at 12 weeks. Key secondary end points were appetite and cachexia symptoms, digital measures of physical activity, and safety.

RESULTS:

A total of 187 patients underwent randomization. Of these patients, 40% had non-small-cell lung cancer, 32% had pancreatic cancer, and 29% had colorectal cancer. At 12 weeks, patients in the ponsegromab groups had significantly greater weight gain than those in the placebo group, with a median between-group difference of 1.22 kg (95% credible interval, 0.37 to 2.25) in the 100-mg group, 1.92 (95% credible interval, 0.92 to 2.97) in the 200-mg group, and 2.81 (95% credible interval, 1.55 to 4.08) in the 400-mg group. Improvements were observed across measures of appetite and cachexia symptoms, along with physical activity, in the 400-mg ponsegromab group relative to placebo. Adverse events of any cause were reported in 70% of the patients in the ponsegromab group and in 80% of those in the placebo group.

CONCLUSIONS:

Among patients with cancer cachexia and elevated GDF-15 levels, the inhibition of GDF-15 with ponsegromab resulted in increased weight gain and overall activity level and reduced cachexia symptoms, findings that confirmed the role of GDF-15 as a driver of cachexia. (Funded by Pfizer; ClinicalTrials.gov number, NCT05546476.).

2024-12-19·NEW ENGLAND JOURNAL OF MEDICINE

Ponsegromab for Cancer Cachexia — A New Dawn for an Old Condition?

作者: Laird, Barry J.A. ; Skipworth, Richard J.E.

项与 Ponsegromab 相关的新闻（医药）

2025-02-04

·FierceBiotech

Pfizer axes B7-H4 ADC, triggering $1B impairment charge as blockbuster vision evaporates

The $200 million impairment charge related to disitamab vedotin reflects the reality of “emerging competition,\" Pfizer said.\n Pfizer has ended development of a B7-H4-directed antibody-drug conjugate (ADC), triggering a $1 billion impairment charge. The Big Pharma disclosed the blow alongside a $200 million charge linked to another ADC. The $1 billion charge is tied to B7H4V, an ADC that Pfizer acquired in its takeover of Seagen late in 2023. Seagen began a phase 1 trial of the ADC in people with advanced solid tumors in 2022. Recruitment stopped in September 2023 but resumed again the next month. Seagen stopped enrollment again in December 2024. Now, Pfizer has revealed the latest halt is permanent. “We have made a business decision to discontinue the felmetatug vedotin (FV) development program based on clinical data generated to date indicating that FV is unlikely to achieve a meaningful improvement over standard-of-care chemotherapy in patients with advanced solid tumors, including triple-negative breast cancer,\" a Pfizer spokesperson said via email. \"There have been no new safety signals observed in patients taking FV.\"Pfizer talked up the prospects of the drug at an oncology day event 11 months ago, including the asset on a list of eight potential blockbusters that its pipeline could generate by 2030. The drugmaker used the event to tout early signs of antitumor activity in patients with two types of breast cancer: triple negative and HER-positive, HER2-negative. At the time, Pfizer was also targeting ovarian and endometrial cancer with the ADC.B7-H4 is a competitive space. AstraZeneca and GSK have rival ADCs in the clinic. Other drug developers have aimed bispecifics at the target but that race has thinned out in recent years, with Pfizer and Genmab terminating programs. Pfizer reported (PDF) the discontinuation of B7H4V as part of $2.9 billion in intangible asset impairment charges in its fourth-quarter results. Another ADC, disitamab vedotin, accounted for $200 million of the charges. Seagen took the HER2-directed ADC into a phase 3 trial in people with previously untreated urothelial cancer in 2023. The ADC, which Seagen bought for $200 million upfront in 2021, works in the same way as Enhertu but AstraZeneca and Daiichi Sankyo’s blockbuster is yet to win approval for first-line use in urothelial cancer. The $200 million disitamab vedotin impairment charge reflects the reality of “emerging competition,” Pfizer said in its financial filing. RemeGen, the biotech that licensed ex-Asia rights to Seagen, won approval for disitamab vedotin in China in 2021. As part of its financials, the New York pharma also revealed it has \"discontinued\" phase 2 work on heart failure hopeful ponsegromab. The drug is still being tested in cancer patients with wasting syndrome to help them gain weight.

抗体药物偶联物上市批准临床1期临床3期临床2期

2025-02-04

·Endpoints

Updated: Pfizer sticks to 2025 projections as Covid sales stabilize, R&D revamp continues

Pfizer’s high-profile, high-volatility Covid-19 franchise stabilized at the end of 2024, as the New York drugmaker pursues a revamp of its R&D operations and continues to cut costs. Pfizer’s Covid pill Paxlovid and its vaccine, Comirnaty, both hit their sales goals for 2024, totaling more than $11 billion in combined sales, the company reported Tuesday . It also reported overall revenue of $63.6 billion for the year, close to the top end of its guidance. CEO Albert Bourla said in prepared remarks that after a year of focusing on costs and resetting its commercial operations, the focus in 2025 “will move to improving R&D productivity.” The company also stuck by its 2025 forecasts issued in December. Pfizer’s R&D work is certain to get extra scrutiny as new chief scientific officer Chris Boshoff continues to make changes. He’s already begun reorganizing the R&D operations, splitting them into independent groups focused on four areas: oncology, vaccines, internal medicine, and immunology and inflammation. That has included some cuts. The company formally culled a late-stage RSV treatment, which Endpoints News first reported in early October, and dropped the pursuit of a second indication for its cachexia drug ponsegromab in heart failure. The heart failure readout was previously delayed from 2025 to 2026. Pfizer also took a $1 billion write-down on a B7H4-directed antibody-drug conjugate acquired in the Seagen purchase. Another $200 million impairment charge was associated with a HER-2-targeting ADC from Seagen, “reflecting emerging competition,” Pfizer noted. Adjusted R&D expenses for the quarter were slightly under $3 billion, 22% below analysts’ consensus. In prepared remarks, CFO Dave Denton attributed that to lower spending on some vaccine programs and “and as a result of our cost realignment program.” When Pfizer announced 2025 guidance, it tacked on $500 million in additional restructuring savings, bringing the total to $4.5 billion. Another $1.5 billion in savings is expected by the end of 2027, after the first phase of a manufacturing overhaul is complete. Fourth-quarter revenue looked significantly better than for 2023, when Pfizer took a one-time, $3.5 billion revenue reversal on Paxlovid related to end-of-the-pandemic product returns by the US government. Paxlovid sales were $727 million in the quarter. The pharma’s RSV vaccine Abrysvo struggled, as has been the case for fellow developers in the vaccines’ second season. Sales were down 62% compared to the fourth quarter of 2023, Pfizer reported. Editor’s note: This story was updated throughout with additional details from Pfizer’s earnings.

疫苗并购IPO抗体药物偶联物

2025-01-20

·药研网

GDF15：肥胖与恶病质治疗的新希望

导语 2025年1月1日，CDE官网公示，劲方医药的GDF-15/IL-6双抗GFS202A注射液的新药临床申请（IND）已经获得NMPA受理，适应症为恶病质。GFS202A为一款GDF15/IL-6双抗。 GDF15是转化生长因子β（TGF-β）超家族的成员之一，与许多疾病有关，包括癌症、炎症和心血管疾病。以GDF15为靶向治疗癌症恶病质及肥胖已被证实是一种很有前景的方法。 GDF15 简介生长分化因子15（Growth differentiation factor 15, GDF15）也被称为巨噬细胞抑制细胞因子（MIC-1）。GDF15作为一种以25 kDa二聚体形式循环的分泌蛋白，由两个含112个氨基酸的多肽链组成，这些链通过二硫键连接，从而形成稳定的结构。 GDF15的生物学功能多样，近年来的研究表明它在炎症反应、细胞应激和代谢调节中起着重要作用。作为一种应激反应因子，GDF15的表达通常在细胞受到损伤或应激时上升，进而调节细胞的生长和分化。 GFRAL（胶质细胞源性神经营养因子家族α样受体）被认为是GDF15的唯一受体，具有重要的生物学意义。当GDF15与GFRAL结合后，形成的复合物随后与辅助受体RET结合，从而激活一系列细胞内信号通路，进一步影响细胞的功能和命运。能够观察到GDNF家族典型的细胞信号，并与RET、AKT、ERK和PLC-γ1的磷酸化相关。这一机制的揭示，为深入理解GDF15在生理及病理状态下的作用提供了新的视角。 GDF15-GFRAL复合物及RET结构图在正常情况下，GDF-15 在大多数器官中低表达，在正常情况下，GDF-15在大多数器官中低表达，肝、肾、心和肺等器官损伤时表达上调。细胞应激以及二甲双胍会导致GDF15的表达升高，引发各种癌症、厌食、体重减轻和新陈代谢的改变。作为免疫检查点，GDF15能抑制DC细胞的成熟，阻碍毒性T淋巴细胞的活化，促进了肿瘤细胞的免疫逃逸。作为代谢调节时，GDF15-GFRAL在非酒精性脂肪肝、心血管等疾病中发挥了重要作用。吉满生物根据市场需求和研究现状，推出稳定表达细胞系、报告基因细胞系以及一系列阳性对照抗体，可用于 GDF15 相关药物的体外效果评价（详细数据见文末），助力抗体药物临床申报。（咨询吉满客服联系同微信：18916119826） GDF-15抑制肿瘤恶病质癌症相关恶病质是指癌症患者在患病过程中不可控制的体重减轻，其症状包括厌食，肌肉量和脂肪组织减少引起的体重减轻。在临床中，50%~80%的癌症患者中会出现称为恶病质的并发症，严重影响患者的生活质量以及临床结局。GDF15的升高与癌症相关恶病质以及癌症的生存期缩短高度相关。 GDF15也被认为是抗肿瘤T细胞活性的负调节因子，与抑制免疫反应有关，并阻止了T细胞被招募到肿瘤微环境中。同时，肿瘤在其微环境中表达并释放大量的GDF-15，这使它能够避免被循环免疫细胞识别并产生抗肿瘤免疫反应。因此，抑制GDF15也是克服癌症标准治疗和免疫治疗（如检查点抑制剂）耐药的重要靶点。 GDF-15治疗肥胖的曙光 GDF15发挥作用需要后脑极后区（AP）和孤束核（NTS）中的受体GFRAL。当GDF15与GFRAL结合时，由于GFRAL胞内区较短，它必须募集共受体RET才能引起胞内信号传递，引起食欲降低和体重减少，并改善胰岛素抵抗和非酒精性脂肪性肝病（NAFLD)。 2017年前后，医学界发现了GDF15在肥胖治疗领域的潜力，礼来、诺和诺德和强生三家制药巨头同时在Nature Medicine明确指出GFRAL是GDF15的高亲和力受体，在减少摄食和降低体重机制中发挥着核心作用。这是科学家们首次确定GDF15调节体重的核心机制和关键受体，为肥胖和Ⅱ型糖尿病的治疗提供了绝佳的靶点。 2023年6月28日，加拿大McMaster大学Dr. Gregory Steinberg课题组的王冬冬博士领导的GDF15研究项目在Nature上发表成果，系统阐释了GDF15通过提高肌肉能量消耗发挥减重作用的机制。连接GDF15与GFRAL和肾上腺素能受体的生物回路的机制图，以在热量限制期间维持肌肉的能量消耗正是因为有越来越多的科学研究证实GDF15在肥胖、糖尿病、非酒精性脂肪肝、癌症等疾病的发病机制中扮演重要角色，其也逐渐成为各药企竞相开发的重要靶点。 GDF15靶点在研格局在全球范围内，GDF-15靶向药物的开发还处于较早期阶段，药物类型以单抗为主，进度较快的属于肿瘤相关疾病的项目，包括CatalYm的Visugromab、辉瑞的ponsegromab以及NGM Bio的NGM120。除单抗外，针对GDF-15靶点的其他药物类型有纳米抗体、融合蛋白、重组蛋白和小分子化药，适应症多为肥胖。 1 GDF-15肿瘤药物开发 CatalYm公司开发的Visugromab是一款人源化的单克隆抗体，旨在中和肿瘤产生的GDF15来抵消免疫抑制机制，增强免疫细胞对肿瘤的浸润，改善DC细胞对T细胞的激活，增强T细胞和NK细胞的肿瘤杀伤作用。在2024ASCO年会上，CatalYm以口头报告形式的公布了Visugromab治疗晚期NSCLC、泌尿系统肿瘤和肝细胞癌的临床2a期试验GDFATHER-2的最新数据。数据显示，Visugromab与抗PD-1抗体Nivolumab联用，在非鳞状NSCLC组中，ORR为19%（4/21）,包括2个PR和2个CR；在尿路上皮癌组中，ORR为19.2%（5/26），包括4个PR和1个CR；在肝细胞癌中，前20明患者的数据显示ORR为20%（4/20），包括3个PR和1个CR。本次临床结果进一步证实了科学家认为通过阻断GDF-15可以增强抗PD-1介导的检查点抑制的疗效的猜想。除GDFATHER-1/2a试验外，CatalYm还在开发Visugromab用于治疗恶病质，目前正处于临床前研究阶段。 AZD8853是一种抗体，旨在针对GDF15蛋白质，用于免疫疗法难以治疗的实体瘤患者。2023年Q1，AZ对部分早期管线进行了削减，AZD8853（I 期）项目被取消。 CDE官网公示，劲方医药的GDF-15/IL-6双抗GFS202A注射液的新药临床申请（IND）已经获得NMPA受理，适应症为恶病质。根据此前劲方医药在IPO招股书中发布的信息来看，该公司在今年12月GFS202A向NMPA提交申请，预计将在2025年第二季度展开临床。辉瑞的Ponsegromab是GDF15的皮下注射用单克隆抗体，在2023 AACR大会上，辉瑞报道了Ponsegromab的Ib期研究数据，参加研究的恶病质患者体重平均增加了6.5%，身体机能也有明显改善；Ponsegromab可将患者体内循环的GDF15水平降低至与健康人群相同。在2024 ESMO大会上、同步发表于《新英格兰医学杂志》的一项重要研究结果显示，ponsegromab在较高用药剂量下可使癌症恶病质患者在12周内恢复约5.6%的体重，食欲、身体活动量和骨骼肌质量均有所改善。与该药物Ib期研究数据比较吻合。 2 GDF15肥胖症药物开发美国强生公司研发的GFRAL激动剂JNJ-9090，其作用机制旨在通过促进产热、脂解作用以及氧化代谢发挥抗肥胖作用，处于临床1期阶段。丹麦诺和诺德公司开发NN-9215(LA-GDF15)为长效GDF15类似物，适应症也为肥胖症,希望通过抑制食欲达到减重目的,目前正在进行I期临床试验。当前处于非积极状态AMG171、LY3463251等在临床I期后因缺乏疗效终止了项目。总结综上所述，靶向GDF-15的临床前阶段药物种类丰富，为未来的药物研发提供了积极的信号。随着对GDF-15在疾病中的作用机制的进一步了解，靶向GDF-15的药物有望成为治疗多种疾病的新型治疗手段，带来新的希望和前景。用心做好细胞，为更好的靶向药吉满生物根据市场需求和研究现状，推出稳定表达细胞系、报告基因细胞系及一系列阳性对照抗体，可用于 GDF15 相关药物的体外效果评价，助力抗体药物临床申报。(咨询吉满客服同微信：18916119826）产品列表数据展示（部分） GM-C06718：H_GDF15 Reporter 293 Cell Line 使用Recombinant Human GDF-15蛋白激活验证结果 GM-C19363：Mouse_GDF15 Reporter 293 Cell Line 使用Recombinant Mouse GDF-15蛋白激活验证结果 GM-C28579：H_GDF15 Reporter 293 DDX35TM Cell Line 使用Recombinant Human GDF-15蛋白各代次稳定性验证结果使用Recombinant Human GDF-15蛋白高低代次三重复验证结果联系我们吉满生物助力药物研发，紧随前沿靶点资讯，储备几百株现货细胞，覆盖GPCR、细胞因子、免疫检查点、TAA等多领域，截止当前已布局近300个热门靶向药靶点，1000余株细胞系，旨在助力、加速大分子早期研发，做到进口细胞的国产替代。同时可根据客户需求提供细胞系服务。扫码咨询扫码找现货

临床申请

100 项与 Ponsegromab 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
厌食症	临床2期	美国	Pfizer Inc.	2022-11-21
厌食症	临床2期	中国	Pfizer Inc.	2022-11-21
厌食症	临床2期	日本	Pfizer Inc.	2022-11-21
厌食症	临床2期	澳大利亚	Pfizer Inc.	2022-11-21
厌食症	临床2期	保加利亚	Pfizer Inc.	2022-11-21
厌食症	临床2期	加拿大	Pfizer Inc.	2022-11-21
厌食症	临床2期	匈牙利	Pfizer Inc.	2022-11-21
厌食症	临床2期	波兰	Pfizer Inc.	2022-11-21
厌食症	临床2期	斯洛伐克	Pfizer Inc.	2022-11-21
厌食症	临床2期	西班牙	Pfizer Inc.	2022-11-21

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05685264 (CTgov)	临床1期	-	18	Ponsegromab (Cohort 1: Ponsegromab 100 mg)	襯壓範構築壓觸願膚築(淵糧鑰夢築願範齋積鑰) = 艱築鏇醖鬱鹽艱襯衊鹹繭築選獵鏇網願範鬱蓋 (積衊顧齋蓋鏇艱鏇齋憲, 58) 更多	-	2024-10-01
NCT05685264 (CTgov)	临床1期	-	18	Ponsegromab (Cohort 2: Ponsegromab 400 mg)	襯壓範構築壓觸願膚築(淵糧鑰夢築願範齋積鑰) = 蓋夢膚鏇壓窪簾鬱鏇鬱繭築選獵鏇網願範鬱蓋 (積衊顧齋蓋鏇艱鏇齋憲, 59) 更多	-	2024-10-01
NCT04803305 (CTgov)	临床1期	卵巢癌 \| 疲劳 \| 恶病质 ... 更多	18	placebo (Placebo)	醖構選範獵淵網齋廠廠(顧壓齋淵鑰選遞膚繭衊) = 選夢獵製鹹襯選構願膚構餘廠餘簾襯積齋壓顧 (構鹹餘蓋鬱選積襯夢願, 蓋鏇廠簾糧壓選鬱網廠 ~ 遞鑰糧醖顧顧範壓選憲) 更多	-	2024-01-12
NCT04803305 (CTgov)	临床1期	卵巢癌 \| 疲劳 \| 恶病质 ... 更多	18	PF-06946860 (PF-06946860 200mg Q3W)	醖構選範獵淵網齋廠廠(顧壓齋淵鑰選遞膚繭衊) = 範積繭簾繭鏇選網簾襯構餘廠餘簾襯積齋壓顧 (構鹹餘蓋鬱選積襯夢願, 餘顧淵鑰餘鑰蓋襯繭憲 ~ 鑰憲鹽淵窪鑰積顧夢獵) 更多	-	2024-01-12
NCT04299048 (CTgov)	临床1期	恶病质 \| 非小细胞肺癌 \| 结直肠癌 ... 更多	11	PF-06946860	選廠鹹糧積壓蓋築齋壓 = 築餘積鏇膚夢糧憲簾範齋廠鹽蓋艱構製鏇願鑰 (壓鬱廠網淵獵膚鑰築觸, 積膚網膚廠醖繭鹽憲築 ~ 鑰憲糧餘鬱鑰製鏇膚願) 更多	-	2023-12-14
NCT04299048 (AACR2023) 人工标引	临床1期	恶病质 \| 肿瘤	10	ponsegromab	鹽糧築廠蓋繭獵膚糧鬱(襯壓鹽範積選鹹餘積齋) = 鹽膚廠鑰窪積鏇獵齋鹽簾網選築醖糧鹽淵鬱獵 (壓製築網壓觸範壓廠齋 )	积极	2023-04-14