Neladalkib

Nuvalent submitted a New Drug Application (NDA) to the US FDA on for neladalkib, an investigational ALK-selective tyrosine kinase inhibitor, seeking approval in patients with TKI pre-treated advanced ALK-positive non-small cell lung cancer. The filing marks the first NDA submission for neladalkib and represents Nuvalent’s initial regulatory filing with the agency. The company said the submission was completed in under four years from first clinical trial initiation, a timeline the company highlighted alongside the drug’s breakthrough therapy designation, which the FDA granted for patients with locally advanced or metastatic ALK-positive NSCLC previously treated with two or more ALK TKIs. Neladalkib has also received orphan drug designation for ALK-positive NSCLC. The NDA is an application for neladalkib in the TKI pre-treated advanced ALK-positive NSCLC population, the company said. The application draws on data from the ALKOVE-1 trial (NCT05384626), a global, first-in-human Phase I/II study enrolling patients with advanced ALK-positive NSCLC and other solid tumors. The Phase I portion evaluated safety, tolerability, pharmacokinetics, and established a recommended Phase II dose of 150 mg once daily. The Phase II portion is a global, single-arm, open-label study designed with registrational intent in TKI pre-treated patients with advanced ALK-positive NSCLC. Topline pivotal data disclosed in November 2025 showed that neladalkib achieved an objective response rate (ORR) of 31% (95% CI: 26–37) in 253 TKI pre-treated patients treated at the recommended dose, as assessed by blinded independent central review. Responses were durable, with 64% and 53% of responders maintaining benefit at 12 and 18 months, respectively. Subgroup analyses indicated higher response rates in select populations, including patients who were lorlatinib-naïve and those harboring ALK resistance mutations such as G1202R, where response rates reached 68%. Intracranial activity was also observed, with responses reported in patients with brain metastases, supporting the drug’s CNS-penetrant design. Across the broader safety population treated at the recommended dose, adverse events were generally manageable, with dose reductions reported in 17% of patients and discontinuations in 5%. Nuvalent said detailed clinical results supporting the NDA will be presented at a future scientific meeting. The submission enters a treatment landscape shaped by six FDA-approved ALK inhibitors spanning three generations. Lorlatinib (Pfizer’s Lorbrena/Lorviqua) is the only approved third-generation ALK TKI and holds a first-line indication approval for patients previously treated with at least one ALK TKI, but no FDA-approved ALK-targeted therapy is specifically indicated for patients who progress after lorlatinib. Chemotherapy is the standard recourse in that setting. Neladalkib is designed to address this gap through a mechanism that distinguishes it from existing agents: it is engineered to retain activity against tumors carrying treatment-emergent ALK resistance mutations, including compound mutations such as G1202R, which emerge following sequential TKI use and are refractory to all currently approved ALK inhibitors. Lorlatinib itself can select for compound mutations upon progression, and these represent a recognized and clinically significant resistance mechanism with no approved targeted solution. The drug’s CNS penetrance is a second design feature relevant to the clinical context. Brain metastases occur in a substantial proportion of ALK-positive NSCLC patients over the course of disease, and intracranial progression remains a cause of treatment failure even with agents that have demonstrated systemic activity. Neladalkib’s reported intracranial responses in the ALKOVE-1 population are therefore of clinical interest, though the magnitude and durability of those responses await formal data presentation. A third distinguishing characteristic is the drug’s selectivity: neladalkib is designed to avoid inhibition of the tropomyosin receptor kinase family, which shares structural similarity with ALK. Dual ALK/TRK inhibition, as seen with lorlatinib, is associated with CNS adverse events including cognitive effects and mood changes that can affect tolerability and dose continuity. A TRK-sparing profile may reduce this class of toxicity, though clinical confirmation is pending full data disclosure. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

约50亿美元！吉利德收购ADC新锐Tubulis 今日，吉利德科学（Gilead Sciences）宣布已与Tubulis达成最终收购协议，吉利德科学将以31.5亿美元首付款收购Tubulis，并可能根据后续里程碑进展支付最高18.5亿美元的额外款项。通过收购Tubulis，吉利德科学将获得多项新一代抗体偶联药物（ADC）管线及技术平台，这些平台旨在更精准地将多种类型载荷递送至肿瘤组织，从而提升治疗效果并改善患者获益。 Tubulis专注于开发新一代ADC，致力于解决肿瘤领域尚未满足的治疗需求。Tubulis的核心在研产品TUB-040是一款靶向NaPi2b的拓扑异构酶I抑制剂（TOPO1i）ADC，目前正在开展针对铂耐药卵巢癌及非小细胞肺癌（NSCLC）的1b/2期临床研究。此外，吉利德科学还将获得另一款靶向5T4抗原的ADC药物TUB-030，该候选疗法已在多种实体瘤中展现出初步临床活性。交易完成后，Tubulis将作为吉利德科学内部专门的ADC研究机构继续运营。 穿越血脑屏障！FDA受理抗癌小分子上市申请 Nuvalent今日宣布，已向美国FDA提交其在研ALK选择性抑制剂neladalkib的新药申请（NDA），用于既往接受过酪氨酸激酶抑制剂（TKI）治疗的晚期ALK阳性非小细胞肺癌（NSCLC）患者。此次申请基于全球注册性ALKOVE-1临床1/2期试验数据。在该研究中，接受neladalkib治疗的TKI经治ALK阳性晚期NSCLC患者表现出令人鼓舞的总体疗效，包括出现颅内应答，同时显示出针对疾病进展关键驱动因素的潜在治疗能力，并呈现出总体耐受性良好的安全性特征。 Neladalkib是一种在研、具有脑部穿透能力的ALK选择性抑制剂，旨在克服现有ALK抑制剂治疗中出现的耐药问题。该药物被设计用于在对第一代、第二代及第三代ALK抑制剂产生耐药的肿瘤中仍保持活性，包括携带单一或复合治疗相关ALK突变（如G1202R）的肿瘤。此外，neladalkib通过实现中枢神经系统（CNS）穿透以改善脑转移患者的治疗选择，同时避免抑制结构相关的TRK受体家族。此前，该疗法已获得FDA授予的突破性疗法认定和孤儿药资格，用于治疗既往接受过两种或以上ALK酪氨酸激酶抑制剂治疗的局部晚期或转移性ALK阳性NSCLC患者。 赛诺菲双特异性纳米抗体2期试验结果公布 赛诺菲（Sanofi）今日公布其在研呼吸系统疗法lunsekimig的2期临床研究结果。该药物是一种新型双特异性纳米抗体，由五个连接的抗体片段构成，旨在同时阻断胸腺基质淋巴细胞生成素（TSLP）和白细胞介素-13（IL-13）两条炎症信号通路，这两种通路被认为是哮喘及相关疾病中导致组织损伤的重要炎症驱动因素。研究结果显示，在两项针对慢性呼吸系统疾病的2期研究中，lunsekimig均达到主要终点及关键次要终点，相比安慰剂显示出明确疗效。同时，在所有研究中该药物整体耐受性良好，安全性特征可接受。 具体来看，在AIRCULES 2b期研究中，lunsekimig在中重度哮喘患者中达到主要终点和关键次要终点，无论患者的生物标志物状态如何均显示疗效。研究结果表明，与安慰剂相比，该疗法可在统计学和临床意义上显著减少疾病急性加重，并改善肺功能指标——支气管扩张剂使用前的一秒用力呼气容积（pre-BD FEV1）。此外，在DUET 2a期概念验证研究中，lunsekimig在慢性鼻窦炎伴鼻息肉（CRSwNP）患者中同样达到主要终点及关键次要终点，在第24周时与安慰剂相比显著改善鼻息肉评分、患者报告的鼻塞/阻塞评分以及Lund-Mackay计算机断层扫描评分。探索性VELVET 2b期研究未在中重度特应性皮炎中达到主要终点，但整体数据仍支持lunsekimig作为呼吸系统疾病治疗候选药物的潜力。 参考资料： [1] Press Release: Sanofi’s lunsekimig met primary and key secondary endpoints in phase 2 respiratory studies in asthma and CRSwNP. Retrieved April 7, 2026 from https://www.globenewswire.com/news-release/2026/04/07/3268809/0/en/Press-Release-Sanofi-s-lunsekimig-met-primary-and-key-secondary-endpoints-in-phase-2-respiratory-studies-in-asthma-and-CRSwNP.html [2] Nuvalent Announces Submission of New Drug Application to FDA for Neladalkib in TKI Pre-treated Advanced ALK-positive NSCLC. Retrieved April 7, 2026 from https://www.prnewswire.com/news-releases/nuvalent-announces-submission-of-new-drug-application-to-fda-for-neladalkib-in-tki-pre-treated-advanced-alk-positive-nsclc-302735124.html [3] Gilead to Acquire Tubulis Adding Potentially Best-in-Class Antibody-Drug Conjugate and Next Generation Platform to Further Strengthen Oncology Pipeline. Retrieved April 7, 2026 from https://www.businesswire.com/news/home/20260406252364/en/Gilead-to-Acquire-Tubulis-Adding-Potentially-Best-in-Class-Antibody-Drug-Conjugate-and-Next-Generation-Platform-to-Further-Strengthen-Oncology-Pipeline 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新