Behcet's uveitis

根据美国证券交易委员会周五发布的文件，诺华公司将终止抗肿瘤坏死因子β抗体 NIS793 的研发，并将其归还给 Xoma 公司。终止开发后，诺华公司将停止所有正在进行的 NIS793 临床研究，但会在这些研究结束后继续收集数据。归还给 Xoma 后，NIS793 仍将作为研究化合物存在。Xoma 公司在提交给美国证券交易委员会的文件中指出：“疗效和安全性尚未确定，我们无法保证 NIS793 能在市场上销售。”NIS793 是全人源单克隆抗体，有望成为卓越的单克隆抗体，通过抑制 TGFβ 细胞因子发挥作用，该细胞因子涉及多个癌症通路，包括转移、血管重塑和免疫逃避。该药物在2021年7月获得美国食品及药物管理局的胰腺癌“孤儿药”认定。自2015年10月以3,700万美元预付款从 Xoma 公司获得 NIS793 使用权以来，诺华一直持有该药物。这项交易还包括高达4.8亿美元的监管和商业里程碑。在终止开发前，诺华正进行 NIS793 治疗胰腺导管腺癌的III期试验，测试该药物与吉西他滨和纳布紫杉醇的联合应用。2017年8月，诺华还以3,100万美元的价格获得了 Xoma 公司抗 IL-1β 抗体 gevokizumab 的全球商业权。在此之前，gevokizumab 在治疗白塞氏病葡萄膜炎的III期试验中失败。诺华正在开发 gevoxizumab，计划于2026年开始提前申报，用于结直肠癌的一线治疗。胰腺癌领域近期取得了重大进展。Exelixis 公司上周终止了针对晚期胰腺和胰腺外神经内分泌肿瘤（NET）的III期CABINET试验，并取消了试验盲区。目前，初次治疗后 NET 患者尚无标准治疗方法，这是一个尚未满足的医疗需求。CABINET 的数据将与监管机构接触，Cabometyx 有望为这些患者提供强有力的治疗选择。益普生于2023年6月宣布，FDA 已接受其将 Onivyde（伊立替康脂质体注射液）扩大至转移性胰腺导管腺癌的一线治疗的补充新药申请。该申请基于III期 NAPOLI 试验数据，显示与纳布紫杉醇和吉西他滨相比，Onivyde 的总生存期和无进展生存期均有显著改善。FDA 预计将在明年初作出裁决。会议推荐

Pictured: Novartis' office in Marburg, Germany/iStock, TBE Novartis is discontinuing the development of the anti-TGFβ antibody NIS793 and is returning it to Xoma Corporation, according to an SEC filing posted Friday. Following the discontinuation, Novartis will stop enrollment into all active clinical studies of NIS793 but will still collect data once these studies have concluded. After returning to Xoma, NIS793 will also remain an investigational compound. “Efficacy and safety have not been established. There is no guarantee that NIS793 will become commercially available,” Xoma wrote in its SEC filing. NIS793 is a fully human and potentially first-in-class monoclonal antibody that works by blocking the TGFβ cytokine, a protein involved in many cancer pathways including metastasis, vascular remodeling and immune evasion. The candidate had previously won the FDA’s Orphan Drug Designation for pancreatic cancer in July 2021. Novartis first gained access to NIS793 in October 2015, when it bought the asset from Xoma for $37 million upfront. The deal also involved up to $480 million in regulatory and commercial milestones. Before ending its development, Novartis was running a Phase III trial for NIS793 in pancreatic ductal adenocarcinoma, testing the candidate in combination with gemcitabine and nab-paclitaxel in the first-line setting. Novartis signed another licensing deal with Xoma in August 2017, gaining worldwide commercial rights to its anti-IL-1β antibody gevokizumab for $31 million. Prior to the deal, the candidate had already failed a Phase III trial for Behcet’s disease uveitis. Novartis is currently developing gevokizumab for the first-line treatment of colorectal cancer, with earlier planned submissions starting in 2026. The pancreatic cancer space has seen major developments lately. Last week, Exelixis stopped and unblinded its Phase III CABINET trial in advanced pancreatic and extra-pancreatic neuroendocrine tumors (NET) following “dramatic improvement” associated with its Cabometyx. There is currently no standard of care for NET patients who progress after initial treatment, representing a large unmet medical need. Cabometyx could potentially present these patients with a strong and effective treatment option. Exelixis will engage regulatory authorities using data from CABINET. In June 2023, Ipsen announced that the FDA had accepted its supplemental New Drug Application, seeking to expand Onivyde (irinotecan liposome injection) into the first-line setting for metastatic pancreatic ductal adenocarcinoma. Its application included data from the Phase III NAPOLI trial, which demonstrated significantly better overall and progression-free survival associated with Onivyde versus nab-paclitaxel and gemcitabine. The FDA’s verdict is due early next year. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.