Nirogacestat hydrobromide

摘要：Immunome 公司宣布，其口服新药 varegacestat 在侵袭性纤维瘤 III 期临床试验中取得突破性成果，疾病进展或死亡风险降低 84%，客观缓解率达 56%，全面达成所有关键终点。该公司计划 2026 年第二季度向 FDA 提交新药申请，这款 γ 分泌酶抑制剂有望成为此类罕见肿瘤的新一代标准疗法，为患者带来全新治疗选择。一、III 期试验大获成功，核心指标全面超预期 12 月 15 日，Immunome 公开了 RINGSIDE 关键试验数据，这款每日口服一次的 varegacestat 表现亮眼。试验结果显示，药物不仅将患者疾病进展或死亡风险大幅降低 84%，满足主要终点要求，在次要指标上也实现全面突破。 其客观缓解率达到 56%，而安慰剂组仅为 9%；同时，药物还显著缩小患者肿瘤体积，并有效减轻疼痛症状，所有关键次要终点均达到统计学显著水平。安全性方面，药物展现出可控的耐受性，最常见不良反应为腹泻、疲劳和皮疹，且多数为 1-2 级轻度反应，未出现严重安全隐患。 作为目前针对侵袭性纤维瘤规模最大、最全面的临床试验，RINGSIDE 试验的阳性结果为药物上市奠定了坚实基础。Immunome CEO 克莱・西格尔表示，这是该患者群体随机临床试验中观察到的最高客观缓解率，凸显了药物的治疗潜力。二、罕见肿瘤治疗困境，新药填补临床空白 侵袭性纤维瘤是一种极具侵袭性的非转移性软组织恶性肿瘤，虽不转移但复发率高，给患者带来严重痛苦。这类肿瘤会引发剧烈疼痛、身体畸形，严重时还会造成危及生命的器官损伤。据统计，美国每年约有 1000 至 1650 人确诊该病，此前治疗选择十分有限。 2023 年 11 月，FDA 批准了 SpringWorks 公司的 Ogsiveo，成为首款针对成人侵袭性纤维瘤的药物。该药物同样属于 γ 分泌酶抑制剂，在 III 期试验中实现 71% 的疾病进展风险降低，客观缓解率为 41%。而 varegacestat 在关键指标上均优于同类药物，有望进一步提升治疗效果。 纪念斯隆・凯特琳癌症中心肉瘤肿瘤学家、RINGSIDE 试验主要研究者姆里纳尔・冈德尔指出，varegacestat 带来的无进展生存期获益、高缓解率和肿瘤体积缩小效果十分显著，这一发现提升了 γ 分泌酶抑制剂的治疗地位。三、2026 年冲刺 FDA，有望成标准疗法 基于优异的试验数据，Immunome 计划在 2026 年第二季度向 FDA 提交 varegacestat 用于治疗进展性侵袭性纤维瘤的新药申请。若获批，这款药物将为患者提供更有效的治疗选择，填补临床需求空白。 冈德尔强调，varegacestat 的试验结果证实，它有望成为侵袭性纤维瘤治疗的标准疗法，为这类罕见病患者带来新的希望。对于缺乏有效治疗手段的侵袭性纤维瘤患者而言，这款药物的上市或将彻底改变疾病治疗格局，减轻疾病带来的痛苦和负担。 目前，Immunome 正推进新药申请的相关准备工作，行业普遍看好药物的获批前景。随着这款潜在重磅新药的推进，侵袭性纤维瘤的治疗将迎来重要突破，为罕见肿瘤治疗领域再添一款利器。 参考来源：https://www.biospace.com/drug-development/immunome-heads-to-the-fda-with-desmoid-tumor-drug-after-phase-iii-sweep 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

Phase 3 data for a gamma secretase inhibitor called varegacestat “looks like a knockout,” Evercore analysts wrote Dec. 15.\n Immunome’s investigational oral therapy has slashed the risk of disease progression or death by 84% for patients with desmoid tumors, data one analyst describes as a “near best-case outcome.”The phase 3 win centers around Ringside, a global study that recruited 156 patients to receive either 1.2 mg daily of Immunome’s varegacestat or placebo until disease progression or death. Varegacestat, a gamma secretase inhibitor (GSI), was also tied to key secondary successes, building up a body of data that “looks like a knockout,” Evercore ISI analyst Cory Kasimov wrote Dec. 15.The findings have Immunome eying a new drug application submission, with an FDA filing expected in the second quarter of next year, according to a Dec. 15 company release.Immunome’s stock has risen 25% from $19.57 per share to $24.54 as of 10:35 a.m. ET today. Zooming in on Ringside, varegacestat significantly improved progression-free survival compared to placebo, showing an 84% reduction in disease progression or death risk, hitting the study’s primary target and delivering what Evercore\'s Kasimov dubbed “very strong topline results.”Varegacestat also delivered an objective response rate (ORR) of 56% based on RECIST v1.1 as compared to a 9% response rate for placebo.This tops the 41% ORR seen in phase 3 development for the current standard of care, Ogsiveo, a GSI sold by Merck KGaA\'s SpringWorks.Immunome’s asset also achieved statistically significant improvements over placebo in reducing tumor volume and pain intensity, the Washington-based biotech said.   Varegacestat was generally well tolerated, with most adverse events of grades 1 or 2 severity, according to Immunome. The most common adverse events occurring in the treatment arm were diarrhea and fatigue, the biotech said.While the adverse event profile looks favorable compared to Ogsiveo, Evercore\'s Kasimov said he\'s interested in more detailed safety data, citing the lack of information in the release about ovarian toxicity, a side effect that can limit treatment for women. Plus, rates of low-grade alopecia were much higher for varegacestat than Ogsiveo in phase 2 development, but no data on the measure were provided today, the analyst wrote.Immunome said it plans to share more data at an upcoming medical meeting. Immunome picked up varegacestat from Ayala Pharmaceuticals last year for $50 million in cash and stock. Should the investigational oral treatment—formerly known as AL102—live up to the hype, Ayala could receive milestone payments of up to $37.5 million.At the time of the deal, Immumone said “data from clinical trials have shown AL102 may be more effective in treating desmoid tumors” than SpringWorks’ Ogsiveo, which secured FDA approval at the end of November 2023.Desmoid tumors are non-cancerous, soft tissue tumors that are prone to recurrence. The tumors are rare, with around 1,000-1,650 Americans diagnosed annually. The condition is known to cause debilitating pain and deformities.“Desmoid tumors can have a devastating physical and emotional impact on patients given their unpredictable nature and the limitations of current treatment options,” Mrinal Gounder, M.D., sarcoma medical oncologist and drug development specialist at Memorial Sloan Kettering Cancer Center, and primary investigator for Ringside, said in the release.“The progression-free survival benefit, high response rate and reduction in tumor volume with varegacestat in the Ringside trial are striking,” Gounder continued. “These findings elevate the role of GSIs and confirm varegacestat could become standard of care in the treatment of desmoid tumors.” Ringside’s phase 3 findings reveal the potential varegacestat has to deliver “best-in-class results in a convenient, once-daily, oral medicine that may help patients reclaim their lives,” Immunome CEO Clay Siegall, Ph.D., said in the release.Siegall took the top spot at the clinical-stage company in 2023 after resigning from his CEO position at oncology powerhouse Seagen in 2022 following an arrest for alleged domestic violence.At the time, the biotech executive was charged with fourth-degree misdemeanor assault and spent 33 hours in jail. The charge was later dismissed due to “insufficient evidence to support filing charges,” according to The Seattle Times.