DAAO

William Blair analysts said they “viewed luvadaxistat development as high risk.” Neurocrine Biosciences’ schizophrenia program pivot has failed. The biotech was unable to replicate the cognition signal it saw in an earlier midphase study, prompting it to stop development of luvadaxistat.San Diego-based Neurocrine in-licensed the DAAO inhibitor luvadaxistat and other R&D programs from Takeda for $120 million upfront in 2020. The next year, a phase 2 trial of luvadaxistat missed its primary endpoint. However, while the candidate failed to improve schizophrenia symptoms on the PANSS scale, Neurocrine did track a significant improvement on secondary endpoints that looked at cognition.The secondary endpoint wins persuaded Neurocrine to run a second phase 2 trial that largely replicated the design of the earlier study. The key difference was the use of the Brief Assessment of Cognition in Schizophrenia as the primary endpoint. Neurocrine included another cognition scale as a secondary goal.This time around, the biotech failed to replicate the cognitive data seen in the earlier trial. Neurocrine said the failure was partly caused by “the large variability seen in the cognitive measures across the population studied and a potential imbalance in the baseline characteristics of subjects enrolled across the treatment arms.” Rather than try to address those issues in a third trial, the biotech has decided to stop development of the drug candidate and focus its resources on other assets. Specifically, Neurocrine plans to pump the money into phase 3 studies of NBI-1117568 for schizophrenia and NBI-1065845 for major depressive disorder.Neurocrine’s share price fell 2% to below $119 in premarket trading, a muted reaction that likely reflects expectations for the program. William Blair analysts said they “viewed luvadaxistat development as high risk” in a note published in response to the failed trial. Neurocrine was open about the risks in the run-up to the readout, too.“Cognitive impairment associated with schizophrenia has been a very, very challenging area. It's about as high risk as you could get, in my view, and there's not a lot known about clinical development in this space because there's such a few number of companies that have worked here,” Kyle Gano, Ph.D., chief business development and strategy officer at Neurocrine, said at a Wells Fargo event last week.There are no FDA-approved treatments for cognitive impairment associated with schizophrenia. Biogen, Roche and Pfizer have studied candidates in the setting but no longer have any active trials. Recognify Life Sciences, an atai Life Sciences company, is running a phase 2 trial that is scheduled to end this year, according to ClinicalTrials.gov.

Second Phase 2 Study for Luvadaxistat Fails to Meet Primary Endpoint as Potential Treatment for Cognitive Impairment Associated with Schizophrenia Results Confounded by Variability in Cognition Measures Across Population Studied and Potential Imbalance in Baseline Characteristics of Enrolled Subjects Neurocrine Biosciences to Focus Resources on Phase 3 Clinical Development of NBI-1117568 for Schizophrenia and NBI-1065845 for Major Depressive Disorder SAN DIEGO , Sept. 12, 2024 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced that its ERUDITE™ Phase 2 clinical study of investigational compound luvadaxistat (NBI-1065844) failed to meet its primary endpoint as a potential treatment to improve cognitive impairment in patients with schizophrenia. The ERUDITE study was the second Phase 2 trial for luvadaxistat. It failed to replicate the cognitive endpoints data seen in the earlier INTERACT™ study, due in part to the large variability seen in the cognitive measures across the population studied and a potential imbalance in the baseline characteristics of subjects enrolled across the treatment arms. In the INTERACT study, 50 mg luvadaxistat resulted in a statistically significant improvement in measure of cognition on the Brief Assessment of Cognition in Schizophrenia (BACS) and cognitive performance on the Schizophrenia Cognition Rating Scale (SCoRS). The INTERACT study represented the first time statistical significance had been demonstrated for both cognitive measure and function within a single study. “While it’s disappointing that luvadaxistat did not meet the primary endpoint in this study, we understand the challenges and hurdles that exist in identifying potential medicines for the treatment of cognitive impairment in schizophrenia. We therefore plan to halt further development of luvadaxistat at this time and instead will focus our efforts and resources on the advancement into Phase 3 clinical development of NBI-1117568 for schizophrenia and NBI-1065845 for major depressive disorder,” said Eiry W. Roberts, M.D., Chief Medical Officer. “We are excited by the opportunity that lies ahead of us to bring forward potential medicines for patients in these important areas of unmet need in neuropsychiatry.” About Luvadaxistat Luvadaxistat (NBI-1065844) is an investigational, oral, selective inhibitor with a high binding affinity to d-amino acid oxidase (DAAO), which metabolizes D-Serine, a primary NMDA receptor co-agonist in the limbic region of the brain. In schizophrenia, N-methyl D-aspartate (NMDA) receptor hypofunction on PV + gamma-aminobutyric acid (GABA) interneurons results in disinhibition of cortical or hippocampal glutamate neurons projecting to the pyramidal neurons, which are associated with cognitive impairment seen in schizophrenia. The ERUDITE™ Phase 2 clinical study is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy safety and tolerability of luvadaxistat in adults with cognitive impairment associated with schizophrenia (CIAS). For more information about this study, visit ClinicalTrials.gov . Neurocrine Biosciences acquired the rights to develop and commercialize luvadaxistat from Takeda Pharmaceutical Company, Ltd. About Schizophrenia Schizophrenia is a serious and complex syndrome with heterogeneous symptoms. This chronic and disabling mental health condition is thought to result from a complex interplay of genetic and environmental risk factors. The World Health Organization estimates that the disorder impacts more than 20 million people worldwide. Annual associated costs for schizophrenia are estimated to be more than $150 billion in the United States . It is estimated that approximately 80 percent of people living with schizophrenia have cognitive impairment associated with schizophrenia (CIAS). About Neurocrine Biosciences Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company’s diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington’s disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com , and follow the company on LinkedIn , X (formerly Twitter) , and Facebook . (* in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo Lockup and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. INTERACT and ERUDITE are trademarks of Neurocrine Biosciences, Inc. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements related to the clinical results from, and our future development plans with respect to luvadaxistat. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: risks that clinical development activities may not be initiated or completed on time or at all, or may be delayed for regulatory, manufacturing, or other reasons, may not be successful or replicate previous clinical trial results, may fail to demonstrate that our product candidates are safe and effective, or may not be predictive of real-world results or of results in subsequent clinical trials; our future financial and operating performance; risks associated with our dependence on third parties for development, manufacturing, and commercialization activities for our products and product candidates, and our ability to manage these third parties; risks that the FDA or other regulatory authorities may make adverse decisions regarding our products or product candidates; risks that the potential benefits of the agreements with our collaboration partners may never be realized; risks that our products, and/or our product candidates may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks associated with U.S. federal or state legislative or regulatory and/or policy efforts which may result in, among other things, an adverse impact on our revenues or potential revenue; risks associated with potential generic entrants for our products; and other risks described in the Company’s periodic reports filed with the Securities and Exchange Commission, including without limitation the Company’s quarterly report on Form 10-Q for the quarter ended June 30, 2024 . Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. View original content to download multimedia: SOURCE Neurocrine Biosciences, Inc.

2024年8月16日，北交所上市公司北京诺思兰德生物技术股份有限公司（股票代码430047）发布公告，其研发的“重组人肝细胞生长因子裸质粒注射液”（代号NL003）治疗下肢缺血性疾病Ⅲ期临床试验静息痛适应症按既定计划揭盲，主要指标符合预期。初步结果表明：主要终点指标180天疼痛完全消失率方面，NL003组显著优于安慰剂对照组（p<0.0001)；安全性良好，两组无明显差异，未发现与药物相关的严重不良反应。这是该公司发布的NL003项目Ⅲ期临床试验第二个方案的初步结果，其首个关键试验溃疡方案于本年2月揭盲，主要指标溃疡完全愈合率方面，NL003组显著优于安慰剂对照组（p<0.0001)，并于7月已正式获得NDA受理申请，进入新药审评程序。 下肢缺血性疾病存在显著的未满足医疗需求 下肢缺血性疾病是临床上常见的一种疾病，通常因动脉硬化闭塞症（ASO）、糖尿病性动脉硬化闭塞症（DAO）和血栓闭塞性脉管炎（TAO）等引发下肢动脉狭窄或闭塞、血流灌注不足，进而导致下肢间歇性跛行、疼痛、溃疡或坏疽等缺血表现。根据缺血程度的不同，临床上采用Rutherford分级，将下肢缺血性疾病从轻到重分为0-6级，其中4-6级属于严重下肢缺血性疾病（CLI），临床症状主要以腿部和脚部静息痛、溃疡及坏疽为主，随疾病的进展，感染、溃疡和坏疽逐渐恶化，严重者将面临截肢甚至死亡。 据中华心血管健康与疾病报告2022报道，在我国35岁以上的自然人群中下肢PAD（外周动脉疾病）的患病率为6.6%，约有4530万例，约10%的下肢PAD患者会进展为 CLI，且CLI发病率高、病程长、致残率高，5年死亡率超过50%，远高于大部分癌症等危重疾病。随着我国社会经济的发展和医疗条件的改善，人均寿命延长，老年人口数量不断增加，老龄化进程加快，未来PAD患病人数预计持续增加，存在显著的未满足医疗需求。 NL003Ⅲ期临床试验主要针对严重下肢缺血性疾病（CLI），分为溃疡（Rutherford 5级）和静息痛（Rutherford 4级）两个适应症分别开展试验。试验采取随机、双盲、安慰剂、平行对照研究机制，以北京协和医院血管外科为组长单位，在全国共24家医院开展临床研究。其中溃疡适应症入组242例、静息痛试验入组302例。溃疡适应症已于2024年2月率先完成试验，并已于7月份正式获得CDE新药注册申请（NDA）受理，是我国首个申报NDA的裸质粒型基因治疗药物。 NL003为国内首款注册申报的裸质粒基因治疗创新药 目前，世界范围内针对CLI尚无有效的治疗药物，临床治疗主要依靠介入及血管搭桥等外科手术方式，治疗手段有限，治疗效果不理想。NL003是一种创新型基因治疗药物，以裸质粒为载体，通过在缺血部位的局部肌肉注射NL003，质粒转染横纹肌细胞并持续表达和分泌具有促进血管生长作用的肝细胞生长因子HGF蛋白，促进新生血管再生，在缺血部位形成侧支循环，建立“分子搭桥”机制，增加缺血部位的血流供应，从而达到疾病治疗作用。与传统的血管重建手术方式比，NL003在创伤性、操作便捷性、病人依从度、疗效和持久性上具有明显优势，可为患者带来持续的临床获益。 生物医药产业是我国战略性支柱产业之一。近日，北京、上海等多地均出台了《关于支持生物医学产业全链条创新发展的若干意见》，加大对创新药械研发的支持，前瞻布局基因与细胞治疗、mRNA等前沿赛道，基因治疗药物更是各大药企争先开发的热点之一。诺思兰德致力于基因治疗药物开发20年，建立了成熟的技术平台，NL003作为我国首款递交NDA申请的基因治疗药物，其研发进度具有国内领先优势。 关于诺思兰德 北京诺思兰德生物技术股份有限公司成立于2004年6月，北交所上市公司，股票代码430047，是一家专业从事基因治疗药物、重组蛋白质类药物和眼科用药物研发、生产及销售的创新型生物制药企业，主要致力于心血管疾病、代谢性疾病、罕见病和眼科疾病等领域生物工程新药的研发和产业化。公司是国家火炬计划重点高新技术企业、北京科技研究开发机构、北京市裸质粒基因治疗药物工程技术研究中心、北京市国际科技合作基地、北京市生物医药产业G20创新引领企业、北京市“专精特新”中小企业。公司拥有授权专利22项，先后承担国家级“重大新药创制”课题8项。 公司坚持以临床需求为导向，建立了基因载体构建、工程菌构建、微生物表达、哺乳动物细胞表达、生物制剂生产工艺及其规模化生产技术以及滴眼剂药物开发等核心技术平台，在临床前研究、临床研究、生产与质量管理、药厂建设、药品经营等方面积累了丰富的经验。 公司药品研发管线丰富且具有较高的成熟度，目前在研11个生物工程新药对应13个适应症。其中重组人肝细胞生长因子裸质粒注射液（代号NL003）已完成临床Ⅲ期研究，溃疡方案已申报NDA；注射用重组人白细胞介素11（代号NL002）处于Ⅲ期临床阶段；注射用重组人胸腺素β4（代号NL005）正在开展Ⅱ期临床研究。公司开发的眼科药品种陆续上市，并有2个进入国家集采。公司稳步发展，目前正在建设生物工程药物生产基地，本年底将具备原液生产条件，实现由Biotech向Biopharm的战略转型。