A phase 3 study of S-812217 in combination with an antidepressant in patients with major depressive disorder consisting of randomized, double-blind, placebo-control part and extension, open-label, re-treatment part

开始日期2022-11-01

申办/合作机构-

JPRN-jRCT2031210577 / Recruiting临床3期IIT

A phase 3 study of S-812217 in patients with major depressive disorder consisting of randomized, double-blind, placebo-control part and extension, open-label, re-treatment part

开始日期2022-03-08

申办/合作机构-

100 项与祖拉诺龙相关的临床结果

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100 项与祖拉诺龙相关的转化医学

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100 项与祖拉诺龙相关的专利（医药）

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项与祖拉诺龙相关的文献（医药）

2024-12-31·Journal of Medical Economics

Indirect comparisons of relative efficacy estimates of zuranolone and selective serotonin reuptake inhibitors for postpartum depression

Review

作者: Deligiannidis, Kristina M ; Toubouti, Youssef ; Gerbasi, Margaret E ; Roskell, Neil ; Smith, Sarah ; Tan, Robin ; Chen, Shih-Yin Sharon ; Meltzer-Brody, Samantha ; Mak, Catherine

AIMSEstimate relative efficacy of zuranolone, a novel oral, Food and Drug Administration-approved treatment for postpartum depression (PPD) in adults vs. selective serotonin reuptake inhibitors (SSRIs) and combination therapies used for PPD in the United States.MATERIALS AND METHODSRandomized controlled trials (RCTs) for zuranolone and SSRIs, identified from systematic review, were used to construct evidence networks, linking via common comparator arms. Due to heterogeneity in placebo responses, matching-adjusted indirect comparison (MAIC) was applied, statistically weighting the zuranolone treatment arm of Phase 3 SKYLARK Study (NCT04442503) to the placebo arm of RCTs investigating SSRIs for PPD. MAIC outputs were applied in Bucher indirect treatment comparisons (ITCs) and network meta-analysis (NMA), using Edinburgh Postnatal Depression Scale (EPDS) and 17-item Hamilton Rating Scale for Depression (HAMD-17) change from baseline (CFB) on Days 3, 15, 28 (Month 1), 45, and last observation (Day 45, Week 12/18).RESULTSLarger EPDS CFB was observed among zuranolone-treated vs. SSRI-treated patients from Day 15 onward. Zuranolone-treated (vs. SSRI-treated) patients exhibited 4.22-point larger reduction in EPDS by Day 15 (95% confidence interval: -6.16, -2.28) and 7.43-point larger reduction at Day 45 (-9.84, -5.02) with Bucher ITC. NMA showed EPDS reduction for zuranolone was 4.52 (-6.40, -2.65) points larger than SSRIs by Day 15 and 7.16 (-9.47, -4.85) larger at Day 45. Lack of overlap between study populations substantially reduced effective sample size post-matching, making HAMD-17 CFB analysis infeasible.LIMITATIONSLimited population overlap between SKYLARK Study and RCTs reduced feasibility of undertaking HAMD-17 CFB ITCs and may introduce uncertainty to EPDS CFB ITC results.CONCLUSIONSAnalysis showed zuranolone-treated patients with PPD experienced greater symptom improvement than SSRI-treated patients from Day 15 onward, with largest mean difference at Day 45. Adjusting for differences between placebo arms, zuranolone may be associated with greater PPD symptom improvement (measured by EPDS) vs. SSRIs.

2024-12-31·Journal of Medical Economics

The cost-effectiveness of zuranolone versus selective serotonin reuptake inhibitors for the treatment of postpartum depression in the United States

Article

作者: Deligiannidis, Kristina M ; O'Callaghan, Lasair ; Johnson, Scott J ; Ferries, Erin ; Chertavian, Elizabeth

AIMSThe objective of this research is to evaluate the cost-effectiveness of zuranolone, the first oral treatment indicated for postpartum depression (PPD) in adults approved by the United States Food and Drug Administration.METHODSZuranolone and selective serotonin reuptake inhibitor (SSRI) trial-based efficacy was derived from an indirect treatment comparison. Long-term efficacy outcomes were based on a large longitudinal cohort study. Maternal health utility values were derived from trial-based, short-form 6-D responses. Other inputs were derived from literature and economic data from the US Bureau of Labor Statistics. We estimated costs (2023 US dollars) and quality-adjusted life-years (QALYs) for patients with PPD treated with zuranolone (14-day dosing) or SSRIs (chronic dosing). The indirect costs and QALYs of the children and partners were also estimated.RESULTSThe incremental cost-effectiveness ratio for zuranolone versus SSRIs was $94,741 per QALY gained over an 11-year time horizon. Maternal total direct medical costs averaged $84,318 in the zuranolone arm, compared to $86,365 in the SSRI arm. Zuranolone-treated adults averaged 6.178 QALYs compared to 6.116 QALYs for the SSRI arm. Costs and utilities for the child and partner were also included in the base case. Drug and administration costs for zuranolone averaged $15,902, compared to $30 for SSRIs over the studied time horizon. Results were sensitive to the model time horizon.LIMITATIONSAs head-to-head trials were not available to permit direct comparison, efficacy inputs were derived from an indirect treatment comparison which can be confounded by cross-trial differences. The data used are reflective of a general PPD population rather than marginalized individuals who may be at a greater risk for adverse PPD outcomes. The model likely excludes unmeasured effects for patient, child, and partner.CONCLUSIONSThis economic model's results suggest that zuranolone is a more cost-effective therapy compared to SSRIs for treating adults with PPD.

2024-12-01·Journal of Psychopharmacology

Cognitive effects, pharmacokinetics, and safety of zuranolone administered alone or with alprazolam or ethanol in healthy adults in a phase 1 trial

Article

作者: Jain, Rakesh ; Dunbar, Joi ; Walling, David P ; Maruff, Paul ; Hassman, Howard A ; Ona, Victor ; Nandy, Indrani ; Moseley, Margaret K ; Levin, Seth ; Czysz, Andy

Background: Zuranolone is an oral, once-daily, 14-day treatment course approved for adults with postpartum depression in the United States. Aims: To assess cognitive effects, pharmacokinetics, and safety of zuranolone, alone or with alprazolam/ethanol. Methods: This was a phase 1, two-part, two-period, randomized, double-blind, placebo-controlled crossover trial. Participants received zuranolone 50 mg or placebo once daily for 9 days, and additionally received alprazolam (1 mg, Part A), ethanol (males: 0.7 g/kg; females: 0.6 g/kg, Part B), or corresponding placebo on days 1, 5, and 9. Within each part, participants received all treatment combinations. Cognition was assessed using a computerized test battery; pharmacokinetics and safety were also evaluated. Results: All participants (Part A, N = 24; Part B, N = 25) received ⩾1 dose of zuranolone/placebo. Compared to placebo, zuranolone produced small-to-moderate cognitive decline (Cohen’s | d| = 0.126–0.76); effects were larger with alprazolam (Cohen’s | d| = 0.523–0.93) and ethanol (Cohen’s | d| = 0.345–0.88). Zuranolone coadministration with alprazolam (Cohen’s | d| = 0.6–1.227) or ethanol (Cohen’s | d| = 0.054–0.5) generally worsened cognitive decline when compared with zuranolone alone. Maximal pharmacodynamic effects occurred at approximately 5 h and were resolved by 12 h postbaseline. No pharmacokinetic interactions were observed. Incidence of adverse events was similar between groups; most events were mild or moderate in severity. Conclusion: A general small-to-moderate magnitude decline in cognition occurred with zuranolone alone. Coadministration with alprazolam/ethanol increased the magnitude, but not the duration, of effects compared with single-agent administration. Zuranolone prescribers and patients should be aware of the potential for increased central nervous system-depressant effects if coadministered with GABAergic active compounds such as alprazolam and ethanol.

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项与祖拉诺龙相关的新闻（医药）

2024-11-18

·Endpoints

A rare neurological disease is Sage’s last, best hope after failures in depression

In 2010, neuroscientist and former Eli Lilly research leader Steve Paul started a company that he hoped would spark a revolution in drug discovery, built around a class of compounds dubbed neurosteroids that could help calm overactive brain circuits and fire up sleepy ones for a long list of psychiatric and neurological conditions. That company, Sage Therapeutics, briefly became one of the hottest tickets in neuroscience. Last year, it won a long-awaited approval for Zurzuvae, the first pill for postpartum depression, a condition that affects one in eight new mothers. But that landmark approval was marred by a sharp downturn in Sage’s fortunes. The FDA rejected the antidepressant’s much broader use in major depressive disorder, for which the data were murky. A slower-than-expected uptake of that pill — and three clinical failures of its other experimental drugs — have sent Sage’s stock down 76% this year, putting its market cap well below the amount of cash it has on hand. Those setbacks spurred two large rounds of layoffs and the departure of several longtime executives. Now, the company’s best shot at a turnaround hinges on a notoriously difficult-to-treat condition: Huntington’s disease, a rare neurodegenerative disorder that causes brain cells to die typically by the time a patient is in their 30s or 40s. Within the next six weeks, it expects to have the results from a Phase 2 study of its neurosteroid-inspired drug dalzanemdor, which Sage once hoped would help treat several neurodegenerative conditions. If the drug succeeds, it could provide Sage a lifeline. Huntington’s patients currently have extremely limited treatment options and, like in postpartum depression, an approval would mark a significant scientific milestone. But if the readout fails, it will prompt a lot of questions for Sage, according to Stifel analyst Paul Matteis. Given how the Zurzuvae story played out — winning a historic approval in postpartum depression but failing to expand that into the larger MDD market — the onus will be on Sage to convince investors it can move the drug forward. “Huntington’s is not necessarily existential for Sage,” Matteis said. “But it could, if it’s negative, start to initiate those types of conversations on, ‘What will actually become of Sage? Why should we have any confidence in the rest of your pipeline?’” Warning signs are already flashing. In July, Sage adjusted the primary endpoint in its Huntington’s trial after a separate study showed only a “small numerical difference” between the dalzanemdor and placebo arms on the primary endpoint, which measures cognitive decline. And dalzanemdor failed to improve cognition in mid-stage studies of two other diseases earlier this year. “Usually when companies have something profound and a remarkable effect size, they lead with it, right? That’s the headline on the press release,” TD Cowen analyst Ritu Baral said in an interview. “And it’s very clear that they did not see on this interim Huntington’s update some sort of blow-the-doors-off signal.” Sage executives have said they believe that Huntington’s disease is where dalzanemdor is most likely to succeed. That said, it’s the only drug in Sage’s pipeline after the company cut its other early-stage research last month. For now, the company is focused on increasing postpartum access to Zurzuvae, which pulled in $11 million in sales in the third quarter. A spokesperson for Sage declined an interview request about the Huntington’s program and what’s next for the company. Paul departed Sage’s board in June. In an interview with Endpoints News , he declined to comment on dalzanemdor or Sage’s future, but he said that even if Zurzuvae is the last drug Sage ever launches, he still views the company as a success. “Quite bluntly, I think people don’t give Sage enough credit for the work they did on zuranalone for postpartum depression,” Paul said. Neurosteroids help fine-tune the effects of GABA and glutamate, the brain’s main inhibitory and excitatory molecules, respectively. These counterparts, sometimes called the yin and yang of the brain, play a role in just about everything that goes on inside our heads. An imbalance between the two systems is implicated in most major psychiatric diseases, including anxiety, depression and schizophrenia. Sage’s work on drugs that enhance GABA receptors led to its sole success in postpartum depression amid failures in major depression, essential tremor and a severe form of epilepsy. Its work on glutamate receptors, specifically enhancing the activity of ones called NMDA receptors, has only led to disappointment so far. Dalzanemdor, previously called SAGE-718, is inspired by a natural neurosteroid called 24(S)-hydroxycholesterol that binds NMDA receptors. It boosts glutamate signaling without directly competing with the neurotransmitter to help stabilize neural networks in the brain. “More than 50 years of research has really suggested that this receptor is a critical node in higher-order cognitive processes, including things like learning and memory,” Sage chief scientific officer Mike Quirk told Endpoints earlier this year. Sage has been testing dalzanemdor in three neurodegenerative diseases, with those readouts marking what Quirk referred to as “a critical inflection point, not just for Sage, but I think also for the field.” The drug failed in Parkinson’s in April and Alzheimer’s in October. Sage executives have repeatedly insisted that there wouldn’t be any read-through from the Parkinson’s trial to the Alzheimer’s study, but analysts viewed success in either disease as a long shot. An added justification for Sage’s final test of dalzanemdor is the imbalance in NMDA signaling in Huntington’s disease that damages neurons. “Mechanistically, if one thing was going to work because of the NMDA mechanism and the NMDA toxicity that’s part of Huntington’s, it was going to be the Huntington's program,” Baral said. A reduction of the natural neurosteroid that dalzanemdor is based on is correlated with cognitive decline in Huntington’s. CMO Laura Gault previously told Endpoints that the drug is designed to improve patients’ cognitive outcomes rather than slow disease progression — a strategy that has worked for some older drugs for treating symptoms of Alzheimer’s. Paul said he still thinks that the drug’s mechanism of enhancing NMDA receptors makes sense. “But there's all kinds of reasons why a drug might not work,” he added. Sage is long past its Wall Street heyday, evidenced by the sharp decline of R&D announcements. In the years immediately following its IPO in 2014, Sage would unveil a new program at seemingly every earnings call, touting its ability to develop a sustainable pipeline and the company itself into a neurology powerhouse. That hasn’t happened, and it remains an open question as to what will happen to the remnants of the R&D engine, Baral said. The investor community feels there is an “opacity” to the R&D platform and whether it can continue to churn out more pipeline programs. Sage employed about 360 people on its R&D team in February 2023. After multiple rounds of layoffs, the remaining group is roughly one-third of its prior size, based on financial filings. The fate of Sage’s early-stage pipeline is even murkier. It doesn’t have anything beyond Zurzuvae and dalzanemdor after a restructuring last month. On its third-quarter earnings call in October, executives alluded to ensuring “longer-term value” but did not provide specifics about any new experimental drugs. A turnaround would have to be driven by CEO Barry Greene. He has consistently wanted to build Sage into the big company that investors want, according to Baral. “Even if Huntington's works, Zurzuvae and a Phase 2 Huntington’s asset is not where he wants Sage,” Baral said. “It's not what he wants for the Sage story in the near- to mid-term.” Sage’s path to success may have been finding a way to get Zurzuvae approved for major depression, an annual market that it estimated is 40 times larger than postpartum depression. Analysts had guided toward $1 billion in peak sales for Zurzuvae in MDD and up to $500 million in postpartum depression. But Sage recently said it would no longer pursue approval for the common condition. In April, two weeks after Paul announced he would step down from Sage’s board, he launched a new company called Seaport Therapeutics. The startup’s lead drug is a novel formulation of allopregnanolone, the same GABA-enhancing neurosteroid used in Sage’s original intravenous infusion for postpartum depression and the inspiration for its more recent pill. Despite Sage’s failed trials, Paul is convinced it will work in major depression. “There’s a lot of evidence that either reduced GABA levels or receptor function is involved in not just postpartum depression, but depression,” he said. “I still believe in the mechanism.”

临床2期上市批准

2024-11-08

·医药魔方Pro

明星药物KarXT开发团队“新冒险”——挑战CNS药物难题 | Seaport Therapeutics

创新是生物医药领域发展的命脉。如何将一项创新技术、一个创新靶点转换为一类创新疗法是科学界、产业界、投资界共同探讨的命题。医药魔方《创星》栏目，根据InvestGO®独有的评分系统，筛选最值得关注的一批“创新之星”，从科学基础、技术优势、研发潜力等多个维度，洞悉新锐公司获资本青睐的原因，同时，也将总结同领域的全球竞争概况，辅助国内创新药同行的决策判断。 2024年9月26日，治疗精神分裂症的创新药物KarXT成功获FDA批准上市。这款药物的问世标志着精神分裂症领域几十年来的重大突破，它采用了全新的作用机制，不依赖传统的多巴胺或5-羟色胺通路，而是作用于中枢神经系统的毒蕈碱乙酰胆碱受体（mAChR）。KarXT由呫诺美林（xanomeline，M1和M4型mAChR激动剂）和曲司氯铵（trospium，外周mAChR拮抗剂）组成，巧妙的复合设计使KarXT在中枢神经系统激活mAChR的同时，又能控制其引起的外周副作用。KarXT在临床上的亮眼表现引起多家MNC的关注，最终在2023年12月，其原研公司Karuna Therapeutics被BMS以140亿美元的价格并购，成为2023年交易额排名第二的并购案例。而就在该交易达成4个月后，孵化Karuna Therapeutics的PureTech Health宣布成立新公司Seaport Therapeutics，开始一场新的冒险。Seaport Therapeutics和Karuna Therapeutics一样专注于中枢神经系统（CNS）药物研发。来源：Seaport Therapeutics官网 Daphne Zohar担任Seaport Therapeutics的创始人兼首席执行官，她之前担任PureTech Health的创始人兼首席执行官并共同创立了Karuna Therapeutics。Daphne Zohar是一位成功的企业家，从16岁时就开始创业，能够敏锐洞察事物的潜在价值。自创立PureTech Health以来，她为公司带来巨大价值。PureTech Health采用的“Hub and Spoke”经营模式使其能够高效推进研发，目前已开发出了28种疗法，在研产品一部分作为内部管线进行开发，另一部分由PureTech Health成立新的实体公司来推进，如Karuna Therapeutics、Seaport Therapeutics。PureTech Health及其成立的实体公司进行的临床试验80%都取得成功，大约是行业平均水平的6倍。 Daphne Zohar（来源：Seaport Therapeutics官网）另一位联合创始人是Karuna Therapeutics前首席执行官、前首席科学官Steven Paul，在加入Karuna Therapeutics之前，Paul曾担任礼来的研发总裁，负责监督奥氮平（Zyprexa）、度洛西汀（Cymbalta）、xanomeline等CNS药物的开发。在他任职礼来期间，xanomeline已经显示出最初的抗精神病和促认知特性。此外，他还联合创立多家CNS领域的创新药物公司，如Sage Therapeutics等，是CNS药物发现和开发领域的权威专家。 Steven Paul（来源：Seaport Therapeutics官网） Seaport Therapeutics不仅汇聚了Karuna Therapeutics的领导团队，还获得了Karuna Therapeutics投资者的支持。2024年4月9日，其宣布完成1亿美元A轮融资，由ARCH Venture Partners、Sofinnova Investments、Third Rock Ventures和PureTech Health共同领投，其中ARCH、Sofinnova和Third Rock都是Karuna Therapeutics的投资者。10月21日，Seaport Therapeutics又完成2.25亿美元B轮融资，A轮投资者继续跟投。半年狂揽3.25亿美元融资，或许是其与Karuna Therapeutics同样的模式及领导团队，让投资人产生了信任。当然，Seaport Therapeutics的技术平台和管线也同样亮眼。公司的核心技术平台Glyph™，源自澳大利亚莫纳什大学Christopher Porter教授及其研究团队的开创性工作。这一平台的独特之处在于它的药物递送机制：通过直接靶向淋巴系统，绕过传统口服药物必须经历的肝脏首过代谢过程，从而显著提高药物的生物利用度、减少潜在的肝脏毒性并提高患者的整体耐受性。Glyph™平台的设计灵感来源于人体对膳食脂肪的自然处理方式，通过将药物与膳食脂肪分子可逆地结合，形成一种新型前药，这种设计允许药物在口服后随同脂肪分子一起绕过肝脏，直接进入肠道的淋巴管系统。Porter研究团队及其合作者在多个顶尖学术期刊上发表了关于Glyph™平台的研究成果，包括Nature Metabolism、Angewandte Chemie和Journal of Controlled Release。这些研究成果详细阐述了Glyph™平台如何通过淋巴系统实现对药物的有效递送，以及这一技术在不同疗法中的应用潜力，证明了该平台的科学严谨性。 Glyph™平台（来源：Seaport Therapeutics官网） Glyph™平台除了科学研究支持，在临床上也得到了验证。Seaport Therapeutics围绕Glyph™设计了多条管线，且管线具有两个特点，一是聚焦患者需求高度未得到满足的领域，二是优先考虑经过临床疗效验证的药物，利用Glyph™技术实现口服并提高生物利用度、降低副作用等。通过这种方式，Seaport Therapeutics能够快速推进管线进展，填补患者需求。管线情况（来源：Seaport Therapeutics官网） Seaport Therapeutics目前主要推进3条管线，其中进展最为迅速的是SPT-300，这是一种别孕烷醇酮（allopregnanolone）口服前药，处于Ⅱ期临床试验阶段，用于治疗产后抑郁、焦虑症、重度抑郁症等。别孕烷醇酮是γ-氨基丁酸-A（GABAA）受体调节剂，具有经临床验证的快速抗抑郁和抗焦虑活性。2019年，Sage Therapeutics研发的布瑞诺龙（brexanolone，人工合成的别孕烷醇酮）获批上市，是FDA首个批准用于治疗产后抑郁症的药物。但它存在过度镇静和意识丧失的风险，因此必须在获得认证的医疗保健中心，留院观察60小时并在加强监护下静脉给药，这无疑给产后抑郁患者的治疗带来了不便。为了改善这一状况，Sage Therapeutics在2023年推出了另一款针对产后抑郁的口服药物珠兰诺隆（zuranolone），通过对别孕烷醇酮进行结构上的优化解决了口服问题，但它仍然面临着肝脏毒性和首过代谢带来的挑战。此外专注于解决药物口服问题的Lipocine也在尝试利用其技术平台开发可口服的别孕烷醇酮，可能也同样面临这些挑战。值得一提的是，Steven Paul曾是Sage Therapeutics的联合创始人，对于布瑞诺龙和珠兰诺隆的开发以及公司其他管线都做出了重要贡献，因此对于别孕烷醇酮的前药开发或许更有经验和见解。SPT-300的Ⅰ期试验结果显示其耐受性良好，别孕烷醇酮暴露量是其他已发表的口服异孕酮数据的9倍，验证了Glyph™平台提高口服生物利用度的能力。在IIa期试验中，SPT-300大大降低了压力诱导的皮质醇水平，治疗焦虑症效果符合预期，且仅有轻微嗜睡的副作用。 SPT-320是阿戈美拉汀的一种新型前药，正准备开展治疗广泛性焦虑症的Ⅰ期临床研究。阿戈美拉汀于2007年上市，可有效治疗广泛性焦虑症和重度抑郁症，且耐受性高。但是其首过代谢高，生物利用度只有约1%，导致一些患者的肝酶增加，需要频繁的肝功能监测。SPT-320使用Glyph™绕过肝脏首过代谢，很有可能降低用药剂量的同时还能提高阿戈美拉汀的有效全身暴露，并且减少对肝功能的损伤以及监护。 SPT-348是一种创新的非致幻性神经原前药，用于治疗情绪和神经精神障碍。非致幻性神经原是CNS药物中的一个新兴领域，通过增强大脑的可塑性来应对这类疾病，同时避免了传统致幻药物可能带来的不良影响。借助于先进的Glyph™技术平台，SPT-348不仅优化了药物的药代动力学特性，还显著提升了其耐受性，这使得它在维持药效的同时，有效地减少了副作用的发生。Seaport Therapeutics在CNS药物领域内积极拓展，除了以上这3条管线，还在开发多个发现和临床前项目。在CNS药物的开发过程中，常常遇到类药性不足或耐受性问题，导致许多有潜力的新型药物未能成功上市，另外尽管有些药物成功上市，但仍然有很多局限性，如给药方式、生物利用度、毒副作用等。面对这些挑战，Seaport Therapeutics的Glyph™平台，展现出了强大的应对能力。Seaport Therapeutics依靠强大的技术平台和优秀的领导团队，极有可能复制KarXT这样的成功案例，为抑郁症、焦虑症以及其他精神疾病的患者带来新的治疗选择和希望。 -上下滑动查看参考资料 - [1]https://karuna-pharmaceuticals.squarespace.com/about [2]https://puretechhealth.com/ [3]https://seaporttx.com/ [4]DOI: 10.1038/s42255-021-00457-w [5]DOI: 10.3389/fphar.2022.879660 [6]DOI: 10.1016/j.jconrel.2021.02.008 创星公司全球 Septerna | Ceptur | Kelonia Sionna | Aspen | Askgene Terremoto | ReCode | CAMP4 Xilis | Dianthus | Aktis | Orna Pretze | Nested | Matchpoint | Vega CARGO | N1 Life | ITM | Genesis Diagonal | Xaira 中国辐联医药 | 瑞石生物 | 阿泰克可瑞生物 | 星奕昂 | 益杰立科迦进生物 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

抗体药物偶联物并购上市批准

2024-11-08

·EndPoints

Legend names a president of Carvykti; Novo Nordisk's top North America exec is stepping down

Alan Bash is joining Legend Biotech as its president of Carvykti , an unconventional, newly-created role to oversee the commercial future of the biotech’s sole marketed cell therapy, among other aspects. Legend is developing Carvykti in partnership with Johnson & Johnson , which reported $286 million in sales in the third quarter. The BCMA-targeted cell therapy is expected to grow into a blockbuster multiple myeloma treatment — in large part as a result of a label expansion to earlier-line patients in April. Legend said in its press release that Bash’s new role will be to oversee Carvykti’s “commercial, technical operations, and quality functions.” Despite impressive results reported from the drug’s clinical studies, Legend and J&J have struggled to meet the commercial demand for the cell therapy. Carvykti has pulled ahead in a field that includes Bristol Myers Squibb ’s Abecma . But it faces an up-and-coming challenger in Gilead and Arcellx : The two companies announced on Tuesday that they had dosed the first patient in a Phase 3 trial of their experimental cell therapy anito-cel , which they say does not come with certain neurotoxicities reported with Carvykti. Bash had joined targeted therapeutics biotech ZielBio as CEO in early 2023. Before that, he was briefly head of Checkmate Pharmaceuticals as the immuno-oncology biotech sold to Regeneron for $250 million in cash. — Lei Lei Wu → Novo Nordisk said in its Q3 report that North America head Doug Langa will step aside at the end of the year “in order to focus on personal priorities and take up a role as senior advisor to Novo Nordisk’s executive management.” Novo has installed corporate development chief Dave Moore as the head of US commercial operations, while CFO Karsten Munk Knudsen will orchestrate the Danish pharma’s corporate strategy. Two days after the FDA declared that Ozempic and Wegovy were available in all doses, Novo’s semaglutide was on the march again, generating positive results in patients with metabolic dysfunction-associated steatohepatitis (MASH) and setting up a possible showdown with Madrigal Pharmaceuticals in an indication also referred to as NASH. → Moderna CEO Stéphane Bancel had been in charge of commercial operations since last December, when the company parted ways with chief commercial officer Arpa Garay . Bancel is now handing over those duties to president Stephen Hoge at Moderna, which made several other changes to its leadership team. Rose Loughlin , the SVP of research and early development, has been elevated to EVP of research. She came to Moderna from Biogen in 2016 as director of business development. Elsewhere, longtime GSK vet Jacqueline Miller has been promoted to CMO at the Covid vaccine titan after she had been SVP and therapeutic area head for infectious diseases. Finally, HR chief Tracey Franklin has expanded the scope of her responsibilities, becoming chief people and digital technology officer. She was chief HR talent and strategy officer at the end of her 14-year career at Merck . Moderna’s late entry into the RSV race produced only $10 million in third-quarter sales for the vaccine, miles behind the market leaders GSK and Pfizer , who haven’t exactly been scorching the nets themselves. But Moderna did turn in a profit as its shares $MRNA received a momentary boost before falling 3% on Thursday. → Axel Sven Malkomes will be the next CFO of German mRNA vaccine maker CureVac on Nov. 11. He succeeds Pierre Kemula , who just started his new CFO gig at Agomab . Malkomes is the ex-finance chief at two other German companies: Cardior Pharmaceuticals , the heart disease biotech that Novo Nordisk bought in March for $1.1 billion; and BioNTech ’s TCR partner Medigene . He’s also a board member at Cellectis . In July, CureVac said it would lay off 30% of its employees as GSK shelled out $429 million upfront for full control of the pair’s flu and Covid vaccine candidates. “It’s never nice to have this kind of news, but I do believe we need to do it now out of a position of financial strength,” CureVac CEO Alexander Zehnder told Endpoints News when the job cuts were announced. → Another notable CFO hire comes from Seaport Therapeutics , the Endpoints 11 winner that followed up its $100 million launch round with a $225 million Series B haul a few weeks ago. Lauren White had held this role for nine months at Elahere developer ImmunoGen , which was purchased by AbbVie for $10.1 billion . She landed her first CFO job at C4 Therapeutics in June 2021 after nine years at the Novartis Institutes for BioMedical Research . Are IPO plans not far behind? Time will tell. “I’m enjoying my brief hiatus as a private CEO right now,” Seaport chief Daphne Zohar said in an interview with Endpoints. → Swedish rare disease specialist Sobi has nominated David Meek as chairman of the board. Not long after Meek’s departure as CEO of Mirati , Bristol Myers swooped in to buy the company and its KRAS drug Krazati to compete with Amgen ’s Lumakras in the space. Meek has also held the top spot at Ipsen and FerGene , and has board seats at uniQure and Cullinan Therapeutics . → Mene Pangalos is the newest board member at Quotient Therapeutics , a Flagship joint that debuted last year and teamed up with Pfizer in August. Since his retirement from AstraZeneca , Pangalos has picked up a board seat at Absci and will join the board of directors at Biogen in January. He’s also on the scientific advisory board at Demis Hassabis ’ Isomorphic Labs. (By the way, check out this week’s Q&A with Hassabis and Andrew Dunn from the Financial Times ’ Global Pharma and Biotech Summit.) → After losing its former CEO Raj Kannan back in July, I-Mab has now locked Sean Fu into the position. Fu has been serving in the interim since Kannan’s exit. Prior to I-Mab, Fu was operating partner of ABio-X and CEO of RVAC Medicines and GeneLeap . Earlier in his career, Fu was with Merck, where he helped lead the integration work of the company following its $42 billion merger with Schering-Plough . It’s been quite a year for I-Mab: Back in April, the company officially spun out its China operations into a new company, I-Mab Biopharma (Hangzhou) , in a bid to win over investors. → Verrica Pharmaceuticals CEO Ted White is out after data for its basal cell carcinoma candidate VP-315 failed to move the needle with investors and job cuts affected 47 staffers. Verrica also drastically reduced its sales presence for its molluscum contagiosum drug Ycanth , from 80 sales territories to 35. In walks Jayson Rieger as president and CEO, and John Kirby as interim finance chief to lead a “leaner and more efficient operating structure,” as chairman Paul Manning put it . Rieger has spent more than a decade with PBM Capital , while Kirby is the former CFO of Aceragen and Idera Pharmaceuticals . → London-based protein degradation biotech Kesmalea Therapeutics has recruited Robert Johnson to steer the Syncona -backed company as CEO. Johnson’s résumé includes stints as CEO of Adrestia Therapeutics (acquired by Insmed ) and co-founder and CBO of Boston-based gene therapy company Affinia Therapeutics . → ElevateBio ’s gene editing sub Life Edit has welcomed Amy Pooler as SVP of R&D. Pooler was VP of neuroscience and head of research in her tenure with Sangamo Therapeutics . While ElevateBio has made eye-popping financing rounds routine, Life Edit formed separate partnerships with Moderna and Novo Nordisk in quick succession last year. → Acumen Pharmaceuticals ’ regulatory affairs leader Janice Hitchcock will retire “at the end of the year,” and Amy Schacterle has been named chief regulatory officer & head of quality at the Alzheimer’s biotech. Schacterle and Acumen president/chief development officer Jim Doherty were colleagues at Sage Therapeutics — Schacterle recently left Sage as part of the latest wave of job cuts after the company said it would no longer develop zuranolone for major depressive disorder. Acumen is testing its monoclonal antibody sabirnetug in patients with early Alzheimer’s. → The latest hires at Dublin-headquartered SynOx Therapeutics are based in the US: Medical chief Elyse Seltzer held multiple roles at GSK and is the former chief development officer at UroGen Pharma , while chief commercial officer Robert Francomano was appointed to the same position at Stemline Therapeutics and Sellas Life Sciences . “We are thrilled to welcome Elyse and Robert to the SynOx leadership team as we continue to work to strategically build out our presence within the key US market,” CEO Ray Barlow said in a statement . SynOx’s $92 million Series B includes a $17 million extension from Gilde Healthcare . → MaaT Pharma has recruited Eric Soyer to succeed Siân Crouzet as finance chief. Crouzet spent the last eight years as CFO and will now be MaaT Pharma’s chief of staff. Soyer had been CFO and COO at another French biotech, Erytech Pharma . His new company’s lead program MaaT013 is in a Phase 3 study for acute graft-versus-host disease. → Frits van Alphen has replaced Gerald Parzmair as chief development officer of Memo Therapeutics , a Swiss biotech that pulled together a total of $49 million for its Series C. After eight years at Novartis , van Alphen would go on to be CMO of Vifor Pharma from 2008-13 and Swiss-based Inositec , the undercard in Vifor’s M&A spree that included Sanifit in late 2021. He also worked for Roche as global head of product development excellence in between these two CMO gigs. → Synthetic lethality player Tessellate BIO has selected Lara Boyd as CBO. Boyd had a six-year run with Takeda partner F-star Therapeutics and was elevated to VP, head of business development & corporate strategy in May 2023. Former F-star boss Eliot Forster chairs the board at Tessellate BIO, which raised $8 million in seed funding from BioGeneration Ventures and Forbion . → La Jolla, CA-based I&I biotech CalciMedica has tapped Stephen Bardin as CFO, replacing interim finance chief Daniel Geffken . Earlier this year, Peer Review covered Bardin’s departure as CFO of atai Life Sciences , a position now held by Anne Johnson . He’s also worked for Myovant Sciences as director of corporate development and BridgeBio as SVP of finance and operations. → Joe Truluck has turned in his resignation as CFO of Adial Pharmaceuticals , and Vinay Shah will replace him on Nov. 16. We told you about Shah’s last CFO appointment at Virpax Pharmaceuticals in June 2023 and he’s had the same title at Aravive . Truluck will stay with Adial as a consultant until March 31. → Claudia Lopez has joined Seattle-based breast cancer biotech Atossa Therapeutics as VP, clinical product development. Lopez led the clinical development team at another AbbVie M&A pickup , Landos Biopharma , and the 16-year Takeda vet also spent two years with Arena Pharmaceuticals . → Tony Gibney has been named chairman of the board at Clearside Biomedical , which unspooled positive Phase 2b data last month for its suprachoroidal injection of axitinib called CLS-AX in patients with wet AMD. Gibney tackled the role of chief business & strategy officer at Iveric Bio until it was sold to Astellas last year for $5.9 billion. → Radiotherapy specialist Actinium Pharmaceuticals has elected June Almenoff to the board of directors. Almenoff, a GSK alum and the ex-president/CMO at Furiex Pharmaceuticals , is also on the boards of Avalo Therapeutics and Tenax Therapeutics . → Heron Therapeutics has reserved a seat on its board of directors for Liquidia CFO and COO Michael Kaseta . Before his gig with Liquidia, Kaseta was CFO at Aerami Therapeutics and Aralez Pharmaceuticals , as well as North American CFO, global services over a decade with Sanofi .

高管变更临床3期疫苗IPO临床2期

100 项与祖拉诺龙相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11793	祖拉诺龙	-	DB15490

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
产后抑郁症	美国	Biogen, Inc.	2023-08-04
产后抑郁症	美国	SAGE Therapeutics, Inc.	2023-08-04

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
产后抑郁症	临床3期	西班牙	Biogen, Inc.	2020-06-08
产后抑郁症	临床3期	英国	Biogen, Inc.	2020-06-08
产后抑郁症	临床3期	英国	SAGE Therapeutics, Inc.	2020-06-08
产后抑郁症	临床3期	西班牙	SAGE Therapeutics, Inc.	2020-06-08
入睡和睡眠障碍	临床3期	美国	Biogen, Inc.	2019-02-04
躁郁症1型	临床3期	美国	Biogen, Inc.	2018-08-23
特发性震颤	临床3期	美国	Biogen, Inc.	2017-03-24
帕金森病	临床3期	美国	Biogen, Inc.	2016-11-30
重度抑郁症	临床3期	美国	SAGE Therapeutics, Inc.	-
重度抑郁症	临床3期	美国	SAGE Therapeutics, Inc.	-

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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


NCT04442490 (CTgov)	临床3期	重度抑郁症	543	Placebo (Placebo)	窪膚窪夢廠獵鬱製築獵(觸鹽觸網構憲願製鑰願) = 糧襯構構鹽鏇顧醖構廠艱壓構獵廠鑰夢蓋網範 (餘淵鹹餘鏇鹹願顧觸鏇, 鹹構窪構壓願顧構淵齋 ~ 範網顧遞齋廠觸壓蓋積) 更多	-	2023-12-05
				SAGE-217 (SAGE-217 50 mg)	窪膚窪夢廠獵鬱製築獵(觸鹽觸網構憲願製鑰願) = 憲鑰簾壓範構鹽構選遞艱壓構獵廠鑰夢蓋網範 (餘淵鹹餘鏇鹹願顧觸鏇, 鏇願衊觸範襯鑰構齋糧 ~ 廠範製構齋觸築襯夢艱) 更多
NCT04476030 (CTgov)	临床3期	重度抑郁症	440	Escitalopram+Matching Placebo+Sertraline+Desvenlafaxine+Duloxetine+Citalopram (Placebo + Assigned ADT)	鑰鏇製淵淵襯憲憲鹽壓(餘壓構選廠鏇顧蓋憲淵) = 鏇願鏇襯憲鏇範餘積衊鬱廠餘選鏇淵壓齋顧簾 (衊鹹獵獵選簾鬱鬱觸積, 簾簾簾鏇觸積鏇蓋糧夢 ~ 願觸廠顧築糧構願繭餘) 更多	-	2023-11-07
				Escitalopram+Sertraline+Desvenlafaxine+Duloxetine+SAGE-217+Citalopram (SAGE-217 + Assigned ADT)	鑰鏇製淵淵襯憲憲鹽壓(餘壓構選廠鏇顧蓋憲淵) = 獵觸製膚衊範觸鑰遞選鬱廠餘選鏇淵壓齋顧簾 (衊鹹獵獵選簾鬱鬱觸積, 範夢鬱鑰範醖構遞鏇蓋 ~ 壓願糧製憲糧範夢構衊) 更多
NCT04442503 (Pubmed \| Am J Psychiatry)	临床3期	产后抑郁症	196	Zuranolone 50 mg/day	繭醖獵製餘膚範遞蓋繭(糧範簾蓋製襯築遞觸夢) = 鑰鑰鑰網蓋蓋鑰選觸顧窪選襯憲顧壓淵網衊願 (觸簾餘願膚繭願築憲襯 )	积极	2023-09-01
				Placebo	繭醖獵製餘膚範遞蓋繭(糧範簾蓋製襯築遞觸夢) = 鑰憲構艱齋艱醖積範網窪選襯憲顧壓淵網衊願 (觸簾餘願膚繭願築憲襯 )
NCT04442503 \| NCT02978326 (FDA) 人工标引	临床3期	产后抑郁症	345	ZURZUVAE 50 mg (Study 1)	(膚蓋糧淵築鹽夢壓壓積) = 膚艱壓願齋選壓獵鹹鬱艱糧窪醖鬱築簾齋選齋 (餘製夢壓蓋鑰範夢範憲, 0.82)	积极	2023-08-04
				Placebo (Study 1)	(膚蓋糧淵築鹽夢壓壓積) = 窪鬱齋選蓋蓋壓鏇網壓艱糧窪醖鬱築簾齋選齋 (餘製夢壓蓋鑰範夢範憲, 0.82)
NCT04442503 (CTgov)	临床3期	产后抑郁症	200	Placebo (Placebo)	構鹹廠範餘顧壓遞夢夢(簾醖鑰顧構鬱衊積憲顧) = 衊夢夢積願壓積鏇餘獵簾顧壓壓艱鹽鏇築衊艱 (廠構齋鹽壓簾積構蓋積, 繭窪製顧網餘觸選簾廠 ~ 遞齋窪繭壓鹹遞鬱壓壓) 更多	-	2023-06-22
				SAGE-217 (SAGE-217 50 mg)	構鹹廠範餘顧壓遞夢夢(簾醖鑰顧構鬱衊積憲顧) = 願獵醖範糧齋構廠憲憲簾顧壓壓艱鹽鏇築衊艱 (廠構齋鹽壓簾積構蓋積, 蓋壓窪製築壓餘糧觸繭 ~ 製遞網艱衊願壓鹽鏇築) 更多
NCT03771664 (CTgov)	临床3期	入睡和睡眠障碍 \| 重度抑郁症	87	Placebo (Placebo)	膚網積壓齋膚窪簾範餘(遞膚製壓獵築醖壓窪鬱) = 鏇願鑰鬱鬱觸範顧繭襯獵壓築膚遞襯鬱遞憲淵 (襯鬱積範糧鑰鹽蓋衊觸, 願餘鹹憲築衊觸膚餘構 ~ 顧選窪簾鑰選壓窪觸鹹) 更多	-	2022-10-20
				SAGE-217 (SAGE-217)	膚網積壓齋膚窪簾範餘(遞膚製壓獵築醖壓窪鬱) = 簾願鹽繭鑰糧鏇選網積獵壓築膚遞襯鬱遞憲淵 (襯鬱積範糧鑰鹽蓋衊觸, 觸淵鹽築積艱餘廠網窪 ~ 醖願衊製構壓範鬱製壓) 更多
NCT04007367 (CTgov)	临床3期	重度抑郁症	53	Placebo (Double-Blind Phase: Placebo)	鹽繭齋顧鬱範簾衊膚願(膚觸鏇鏇夢遞襯選構糧) = 積壓夢蓋齋襯繭糧廠積選獵網壓築繭齋獵衊顧 (齋構窪鑰鹹壓廠齋餘衊, 鬱觸觸鬱憲選壓糧網製 ~ 淵窪衊壓憲鑰憲鑰糧鑰) 更多	-	2022-10-03
				SAGE-217 (Double-Blind Phase: SAGE-217)	鏇餘簾蓋醖壓繭鏇積鏇(獵衊積鑰鑰鹹鹽窪積鹹) = 夢觸鑰糧選夢製廠製製鹽築鹽衊顧製鹹廠獵鹽 (壓襯選繭糧膚糧製鏇鬱, 鬱蓋顧顧艱簾選製艱願 ~ 襯網壓夢鏇鹽糧構醖範) 更多
NCT03864614 (SHORELINE, Corporate Publications) 人工标引	临床3期	重度抑郁症	924	Zuranolone (30mg cohort)	(襯襯憲築觸鏇餘鏇範範) = there was a mean reduction in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score from baseline to Da15 網餘餘築鬱蓋夢餘壓顧 (膚衊獵廠遞願蓋築憲鑰 )	积极	2022-09-19
				Zuranolone (50 cohort)
NCT02978326 (CTgov)	临床3期	产后抑郁症	276	SAGE-217 15/20 mg Oral Solution (Part A: SAGE-217 15/20 mg Oral Solution)	窪衊衊壓齋繭獵餘觸鑰(蓋製積齋鏇遞製蓋繭網) = 壓衊糧憲衊選繭夢糧範襯糧齋憲壓醖繭範鏇獵 (夢鹽遞襯顧襯製襯簾遞, 憲窪齋艱憲餘夢鹹窪獵 ~ 顧網夢糧築獵構願蓋鹽) 更多	-	2021-12-16
				Placebo (Part B: Placebo)	壓積壓簾夢鏇築積範選(淵鬱淵廠觸製襯築積糧) = 壓鑰觸顧蓋獵齋製糧膚淵願膚築膚膚蓋壓醖艱 (窪繭襯淵觸鑰構構積鬱, 蓋襯壓衊構廠獵選顧簾 ~ 壓願衊艱繭鏇襯糧簾獵) 更多
NCT02978326 (Pubmed \| JAMA Psychiatry) 人工标引	临床3期	产后抑郁症	153	Zuranolone	(選蓋齋顧鬱鹹範窪積簾) = 壓襯壓範鑰構憲艱鑰膚繭淵壓觸繭艱壓簾顧夢 (鹽窪襯鬱構鑰鏇網蓋襯 ) 更多	积极	2021-09-01
				Placebo	(選蓋齋顧鬱鹹範窪積簾) = 願夢夢憲鬱繭齋艱糧壓繭淵壓觸繭艱壓簾顧夢 (鹽窪襯鬱構鑰鏇網蓋襯 ) 更多