A Randomized, Double-blind, Phase 3 Study Comparing Efficacy and Safety of Frexalimab (SAR441344) to Placebo in Adult Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis

The purpose of this randomized, double-blind, placebo-controlled, parallel group study is to determine the efficacy of frexalimab in delaying the disability progression and the safety up to approximately 51 months administration of study intervention compared to placebo in male and female participants with nrSPMS (aged 18 to 60 years at the time of enrollment). People diagnosed with nrSPMS are eligible for enrollment as long as they meet all the inclusion criteria and none of the exclusion criteria. Study details include:
This event-driven study will have variable duration ranging from approximately 27 to 51 months.
The study intervention duration will vary ranging from approximately 27 to 51 months.
The number of scheduled visits will be up to 27 (including 3 follow-up visits) with a visit frequency of every month for the first 6 months and then every 3 months.

开始日期2023-12-27

申办/合作机构

Sanofi

NCT06141473 / Recruiting临床3期

Master Protocol of Two Independent, Randomized, Double-blind, Phase 3 Studies Comparing Efficacy and Safety of Frexalimab (SAR441344) to Teriflunomide in Adult Participants With Relapsing Forms of Multiple Sclerosis

The purpose of each study is to independently measure the annualized relapse rate (ARR) with administration of frexalimab compared to a daily oral dose of teriflunomide in male and female participants with relapsing forms of multiple sclerosis (aged 18 to 55 years at the time of enrollment). People diagnosed with relapsing forms of multiple sclerosis are eligible for enrollment as long as they meet all the inclusion criteria and none of the exclusion criteria.
Study details include:
This event-driven study will have variable duration of approximately 40 months for the first participant being randomized and approximately 20 months for the last participant randomized.
The study intervention duration will vary ranging from approximately 20 to 40 months.
The assessment of scheduled visits will include 1 common end of study [EOS] visit and 3 follow-up visits) with a visit frequency of every 4 weeks for the first 6 months and then every 3 months.

开始日期2023-12-13

申办/合作机构

Sanofi

NCT06111586 / Recruiting临床2期

A 52-week Randomized, Double-blind, Placebo-controlled, Multi-center Phase 2b Study With a 52-week Blinded Extension Assessing Safety and Efficacy of Frexalimab, a CD40L-antagonist Monoclonal Antibody, for Preservation of Pancreatic β-cell Function in Adults and Adolescents With Newly Diagnosed Type 1 Diabetes on Insulin Therapy

This is a randomized, parallel group, double-blind Phase 2 study that consists of 2 parts. In Part A the safety of the highest dose-level of frexalimab in adults (age range 18-35 y.o.) will be established. In Part B, a dose-finding study (adolescents and young adults, 12-21 y.o.) evaluating the safety and efficacy of 3 age-adjusted dose-levels of frexalimab in comparison with placebo in participants with newly diagnosed T1D on insulin treatment. The purpose of this study is to determine safety and efficacy of different dose-levels of frexalimab, by assessment of preservation of endogenous insulin secretion in participants with newly diagnosed T1D aged 12 to 21 years compared with placebo on top of standard insulin therapy, and to determine the dose-response relationship and minimal efficacious dose in Part B. Study details include: - Screening period: at least 3 weeks and up to 5 weeks (Up to 11 days may be required to get investigational medicinal product [IMP] on site. Enrollment date of the participant must take into consideration this constraint.) - Double-blind treatment period (104 weeks): -- Main treatment period: 52 weeks -- Blinded extension: 52 weeks - Safety follow-up: 26 weeks (not applicable for participants entering the open-label study) The treatment duration will be up to 104 weeks, the total study duration will be up to 135 weeks.

开始日期2023-12-11

申办/合作机构

Sanofi

100 项与 Frexalimab 相关的临床结果

登录后查看更多信息

100 项与 Frexalimab 相关的转化医学

登录后查看更多信息

100 项与 Frexalimab 相关的专利（医药）

登录后查看更多信息

项与 Frexalimab 相关的文献（医药）

2023-08-01·Nature medicine1区 · 医学

Anti-CD40L antibody frexalimab slows new brain lesions in multiple sclerosis.

1区 · 医学

作者: Carvalho, Thiago

项与 Frexalimab 相关的新闻（医药）

2024-04-28

·生物制药小编

两大药企相继砍去多条早期管线

4月25日（近日），赛诺菲和阿斯利康各自在其2024年Q1财报中削减了不同数量的早/中期管线，本文将对这些被削减管线的靶点进行简单分析，期望对于这些未解明靶点的不完全解读对该靶点的未来发展情况做出一定贡献。CD40L抗体一项适应症遭到暂停在肿瘤赛道多年的沉寂以来，自免赛道的CD40L抗体Frexalimab的开发在赛诺菲这看到了曙光，在多发性硬化症中的优异数据让Frexalimab成为了该赛道的风口。此次有一项适应症被放弃对赛诺菲来说影响并不大，只是干燥综合征的赛道被放弃了，考虑到干燥综合征本身就是一项发病机制尚且不明的自免疾病。CD40L抗体的如果成功了或许因为这项疾病患者人数不少也会有高额回报，失败了也并不会产生巨额亏损，因此被放弃可以说是意料之中。难以奏效的VenglustatVenglustat的设计初衷是为了应对那些特定类型的糖脂代谢异常疾病的，其机制是通过抑制葡萄糖神经酰胺合成酶（glucosylceramide synthase, GCS）来减少有害鞘脂物质在体内堆积。而GM2神经节苷脂贮积症的病因是由溶酶体中β-氨基己糖苷酶（Hex）缺乏导致的GM2神经节苷脂不能被有效降解。因此，即便阻断了有害鞘脂物质在体内堆积，但仍然是“治标不治本”。确实可以预见到缺乏疗效。RIPK1抑制剂在ALS赛道中的否决作为用途广泛的细胞凋亡通路，RIPK1抑制剂的开发多种多样，不过之前的早期开发也有很明显的失败案例，DNL747和DNL104都因为毒性问题而被迫终止。赛诺菲在RIPK1抑制剂上的Denali公司迭代开发上选择了两条路，一条是自免赛道，一条是神经退行性疾病方面，但无论是哪种开发方式，对于RIPK1抑制剂都是全新的开发方向。此次ALS方向上的失败，也对这一赛道的后继者给出了警示。被优化掉的MEDI6570MEDI6570是一款LOX-1靶向单克隆抗体，用于阻断LOX-1受体的多种配体，目前的适应症是心肌梗死。LOX-1途径代表着PCSK9以外的另外心血管治疗靶点之一，但显然这一推入II期临床的项目遭到了优化。从机制上来看，凝集素样氧化低密度脂蛋白受体1（LOX-1）作为一种清道夫受体，能够结合多种已知致动脉粥样硬化的配体，包括氧化低密度脂蛋白、功能障碍的高密度脂蛋白、C反应蛋白、晚期糖基化终产物、活化血小板和凋亡细胞。阻断结合被认为有可能防止冠状动脉粥样硬化的斑块的产生，降低血管内的炎症。但一个很现实的问题也在MEDI6570研究的文献中展示了：可溶性LOX-1水平是下降了，可除了MEDI6570与斑块非钙化斑块体积的无显著性回归相关以外，他们甚至无法将血管炎症指标量化。当时，研究人员使用了一种新的血管炎症测量方法，即CTA扫描的血管周FAI。与CTA衍生的斑块测量值相比，FAI被认为是血管炎症的更特异性标志物和心血管死亡率的预测因子。然而，在I期二型糖尿病患者人群中，几乎所有患者的FAI基线测量值都在正常范围内，因此无法评估MEDI6570对冠状动脉血管特异性炎症的影响。需要进一步的研究来调查血清sLOX-1水平的降低是否会对冠状动脉血管炎症和斑块体积产生下游影响。考虑到临床数据的有效性其实非常有限，该管线被砍去具有一定合理性。AZD7503：或是“兄弟管线”做太好了？另外一款被阿斯利康砍去的是AZD7503（ION455），该管线是阿斯利康从Ionis那里获得的配体偶联反义寡核苷酸（LICA）药物，旨在抑制17β-羟基类固醇脱氢酶13（HSD17B13）蛋白的产生，适应症选择的是非酒精性脂肪性肝炎。之前有来自赫尔辛基大学和耶鲁大学的研究团队发现，抑制HSD17B13能够通过抑制非酒精性脂肪性肝炎患者的嘧啶分解代谢来防止肝纤维化，当时在小鼠模型中他们采用的是AAV8-GFP-U6-m-HSD17B13-shRNA和AAV8-GFP-U6-scrmb-shRNA（对照组）两种用于产生shRNA的AAV来达到对比效果。然而，早期临床项目的AZD7503早早被放弃……有可能是因为同样是Ionis授权给阿斯利的“兄弟管线”ION224同样也在非酒精性脂肪性肝炎里做得太好：上个月ION224用于代谢功能障碍相关脂肪性肝炎（MASH）的II期研究达到主要终点，在120mg和90mg两种剂量下均能实现肝脏组织学改善。考虑到这一情况，阿斯利康和Ionis或许是权衡之下觉得没必要将过多的资源投入还未有确定结论的AZD7503？AZD5055AZD5055（RXC006）是2020年8月Redx公司与阿斯利康总额3.7亿美元交易的产物，现在算是被阿斯利康退货了，该药物机制是靶向porcupine(Wnt途径的组分酶，Wnt信号通路常常和损伤修复相关)来治疗纤维化疾病。这款管线的问题可以从近期发表的一篇文献中看出。该研究中，另外一款porcupine抑制剂LGK974在对照小鼠中引起了显著的骨质流失，抑制Wnt通路可减少纤维化骨鼠模型中的骨小梁而不能改善纤维化。是否在肺纤维化中也会遇到类似情况不得而知。但至少porcupine抑制剂会引起骨丢失这一问题相当致命……总结总的来说，这些早期管线的被裁对后续相关管线的企业可能具有一定警醒作用，在设立相关管线之前值得三思。参考来源：1.Manfrè V, Chatzis LG, Cafaro G, Fonzetti S, Calvacchi S, Fulvio G, Navarro Garcia IC, La Rocca G, Ferro F, Perricone C, Bartoloni E, Baldini C. Sjögren's syndrome: one year in review 2022. Clin Exp Rheumatol. 2022 Dec;40(12):2211-2224. doi: 10.55563/clinexprheumatol/43z8gu. Epub 2022 Dec 20.2.Luukkonen PK, Sakuma I, Gaspar RC, Mooring M, Nasiri A, Kahn M, Zhang XM, Zhang D, Sammalkorpi H, Penttilä AK, Orho-Melander M, Arola J, Juuti A, Zhang X, Yimlamai D, Yki-Järvinen H, Petersen KF, Shulman GI. Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis. Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2217543120. doi: 10.1073/pnas.2217543120. Epub 2023 Jan 20.3.Vavere AL, Sinsakul M, Ongstad EL, Yang Y, Varma V, Jones C, Goodman J, Dubois VFS, Quartino AL, Karathanasis SK, Abuhatzira L, Collén A, Antoniades C, Koren MJ, Gupta R, George RT. Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Inhibition in Type 2 Diabetes: Phase 1 Results. J Am Heart Assoc. 2023 Feb 7;12(3):e027540. doi: 10.1161/JAHA.122.027540. Epub 2023 Jan 23. Erratum in: J Am Heart Assoc. 2023 Mar 21;12(6):e027644.4.https://www.ionispharma.com/medicines/ion455/5.https://www.redxpharma.com/wp-content/uploads/2018/12/Redx-signs-out-licensing-agreement-with-AstraZeneca.pdf6.http://www.firstwordPharma.com/node/1604627#axzz5WvWo4v357.Lung H, Wentworth KL, Moody T, Zamarioli A, Ram A, Ganesh G, Kang M, Ho S, Hsiao EC. Wnt pathway inhibition with the porcupine inhibitor LGK974 decreases trabecular bone but not fibrosis in a murine model with fibrotic bone. JBMR Plus. 2024 Jan 21;8(5):ziae011. doi: 10.1093/jbmrpl/ziae011.

财报临床1期临床2期临床终止引进/卖出

2024-04-25

·FierceBiotech

Sanofi crosses Sjögren's off $5B drug's hit list after phase 2 data disappoint

Sanofi revealed a setback alongside news of another blow to venglustat. Sanofi is narrowing development of one of its 5 billion euro ($5.4 billion), “pipeline-in-a-product” assets. The French drugmaker axed Sjögren’s syndrome from the list of targeted indications for frexalimab after seeing phase 2 efficacy data—and reported a phase 3 flop for one of its tarnished former top prospects. Frexalimab is a CD40L monoclonal antibody that cleared a midphase test in multiple sclerosis (MS) last year. The readout suggested Sanofi may have found a way around the blood clot risks that blighted earlier CD40 drug candidates. Encouraged, Sanofi pushed ahead with phase 3 studies in two forms of MS and midstage trials in Type 1 diabetes and systemic lupus erythematosus. The company began comparing frexalimab, also known as SAR441344, to placebo in Sjögren’s in 2020. The goal was to show whether the candidate can improve scores on a Sjögren’s disease activity scale. Sanofi revealed the molecule fell short as part of its first-quarter results (PDF) Thursday. “The data confirmed pharmacologic activity and well-tolerated safety profile but not the necessary efficacy outcomes to continue to move forward the development in this indication,” Sanofi said. The findings of the 84-patient phase 2 trial persuaded Sanofi to stop development in Sjögren’s. Development in other, potentially more lucrative indications is continuing. Sanofi revealed the setback alongside news of another blow to venglustat, a GCS inhibitor that has slipped down the pecking order in recent years. Venglustat was among the assets that Paul Hudson identified as Sanofi's top prospects when he took over as CEO in 2019. However, the drugmaker stopped a phase 2/3 trial in autosomal dominant polycystic kidney disease in 2021. The failure came months after venglustat missed the mark in a phase 2 Parkinson’s disease study. While the failures dented Sanofi’s “pipeline in a pill” ambitions, work continued in GM2 gangliosidosis, Gaucher disease type 3 and Fabry disease. Thursday, Sanofi crossed GM2 off the list of active indications “based on the absence of positive trends on clinical endpoints.” Sanofi said the phase 3 GM2 trial “reinforced the favorable safety profile” of venglustat. Development is continuing in Fabry and Gaucher, settings in which Sanofi could file for approval in 2025 and beyond.

临床3期临床2期临床失败

2024-04-25

·Firstwordpharma

All eyes on Dupixent decision in COPD as Sanofi suffers further pipeline setbacks

Sanofi said Thursday that Dupixent remains on track to record sales of around €13 billion this year after posting strong growth in the first quarter ahead of an expected expansion into chronic obstructive pulmonary disease. Revenue from Dupixent jumped 22.4% in the three-month period to €2.8 billion.The performance of Dupixent, along with Beyfortus (€182 million) and Altuviiio (€122 million), helped the company top expectations, with overall sales rising 2.4% to €10.5 billion, ahead of forecasts of €10.3 billion. However, net income plunged 43.2% to €1.1 billion.Sanofi reiterated its expectation that earnings this year will decrease by a low single-digit percentage at constant currencies. CEO Paul Hudson has braced investors for a period of slower growth over the next few years as the company directs resources into its drug-development, betting on 12 pipeline medicines including amlitelimab, frexalimab and tolebrutinib that it says have blockbuster potential.Pipeline setbacksHowever, Sanofi’s ambitions for frexalimab took a hit on Thursday after the company disclosed that development in Sjögren’s syndrome has been halted. Results from a Phase II trial failed to meet the “necessary efficacy outcomes” to continue to work in this indication, the drugmaker said, noting that Phase III studies of the anti-CD40L antibody in relapsing multiple sclerosis and secondary-progressive multiple sclerosis will continue, as well as mid-stage development in type 1 diabetes and systemic lupus erythematosus.Sanofi also disclosed Thursday that the Phase III AMETHIST trial of the GCS inhibitor venglustat for the treatment of GM2 gangliosidosis was discontinued based on “the absence of positive trends” for clinical endpoints. The company also confirmed the discontinuation of the RIPK1 inhibitor oditrasertib - announced by partner Denali Therapeutics in February – in amyotrophic lateral sclerosis.More to come.

临床2期临床3期财报临床失败上市批准

100 项与 Frexalimab 相关的药物交易

登录后查看更多信息

研发状态

适应症	最高研发状态	国家/地区	公司
复发性多发性硬化	临床3期	美国更多	Sanofi 更多
1型糖尿病	临床2期	美国更多	Sanofi 更多
系统性红斑狼疮	临床2期	西班牙更多	Sanofi 更多
原发性干燥综合征	暂停	德国更多	Sanofi SA 更多
Sjogren-Larsson综合征	无进展	匈牙利更多	Sanofi 更多

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


NCT04879628 (Corporate Publications) 人工标引	临床2期	多发性硬化症	112	frexalimab 1200 mg	糧願醖鏇鑰範鹽廠淵衊(膚選艱鏇鹽膚齋構遞醖) = 艱夢鬱齋齋鏇獵醖壓蓋築築膚簾窪醖簾醖願積 (繭構衊繭繭糧築觸鹹鬱 ) 更多	积极	2024-04-17
				frexalimab 300 mg	糧願醖鏇鑰範鹽廠淵衊(膚選艱鏇鹽膚齋構遞醖) = 顧顧製繭齋艱構廠選憲築築膚簾窪醖簾醖願積 (繭構衊繭繭糧築觸鹹鬱 ) 更多
NCT04879628 (Literature) 人工标引	临床2期	多发性硬化症	129	frexalimab 300 mg	網窪膚窪獵願顧廠繭淵(蓋憲鏇鬱築餘鑰鏇壓鬱) = 憲窪鏇膚蓋製鑰艱齋範餘簾願襯夢鏇觸觸築夢 (廠鏇獵糧淵顧醖構夢繭, 0.1 ~ 0.6)	积极	2024-02-15
				frexalimab 1200 mg	網窪膚窪獵願顧廠繭淵(蓋憲鏇鬱築餘鑰鏇壓鬱) = 廠鑰簾壓鏇窪顧繭獵築餘簾願襯夢鏇觸觸築夢 (廠鏇獵糧淵顧醖構夢繭, 0.1 ~ 0.4)
NCT04879628 (GlobeNewswire) 人工标引	临床2期	复发性多发性硬化	129	frexalimab (high-dose)	膚糧廠顧憲襯齋夢選積(繭鑰網鹽壓繭淵衊壓製) = 衊積衊夢糧廠鏇築艱壓顧鬱餘夢壓齋糧壓鑰憲 (餘鑰膚觸構網淵糧遞鬱, -62 ~ -97) 达到更多	积极	2023-05-31
				placebo (high-dose)	-