Mavorixafor

今日全球医药研发领域的事件主要集中在后期临床失败、肥胖代谢早期人体数据、体内基因编辑、CAR-T注册性研究和关键监管沟通等方面。 今日事件速览 药物/项目 公司 今日进展 一句话看点 del-desiran Novartis Ⅲ期HARBOR失败 DM1关键Ⅲ期未达主要终点，AOC核心资产遭遇重大挫折 ACCG-2671 Structure Therapeutics Ⅰ期首次人体数据 单次10 mg后Day 24平均减重3.3%，半衰期约6天 BEAM-302 Beam Therapeutics Ⅰ/Ⅱ期数据更新 体内碱基编辑后AAT超过保护阈值，最长随访达18个月 arlo-cel Bristol Myers Squibb 注册性Ⅱ期阳性 GPRC5D CAR-T达到ORR和CR主要终点，瞄准BCMA治疗后MM NouvSight001 睿健医药 中美IND双批（9月7日） 通用现货型光感受器细胞疗法同步进入中美临床开发 mavorixafor X4 Pharmaceuticals FDA重要监管决定 FDA同意Ⅲ期样本量由176例降至126例，并认可拟议安全数据库 今日关键词Ⅲ期失败首次人体Amylin体内碱基编辑GPRC5D CAR-T现货型细胞治疗FDA临床设计 01｜Novartis del-desiran：DM1关键Ⅲ期HARBOR研究失败 Novartis宣布delpacibart etedesiran（del-desiran）治疗1型强直性肌营养不良（DM1）的全球Ⅲ期HARBOR研究未达到主要终点：与安慰剂相比，视频手部张开时间（vHOT）未实现统计学显著改善。该药通过AOC平台递送siRNA、降低致病DMPK RNA。虽然部分次要和探索性终点观察到临床活性，安全性与此前数据基本一致，但公司将重新分析完整数据并与监管机构讨论开发路径。 研发看点 这是今天优先级最高的一条。后期Ⅲ期失败的权重远高于一般早期数据更新，而且DM1目前仍缺乏获批的疾病修饰疗法。下一步关键是判断vHOT失败究竟来自药物机制不足、终点选择问题，还是患者异质性。 来源：Novartis官方公告 https://www.novartis.com/news/media-releases/novartis-provides-update-delpacibart-etedesiran-del-desiran-phase-iii-harbor-study-treatment-myotonic-dystrophy-type-1-dm1 02｜ACCG-2671：首个口服小分子Amylin项目公布Ⅰ期人体数据 Structure Therapeutics公布ACCG-2671Ⅰ/Ⅱa期SAD首次人体数据。该药是一款口服、非肽类Amylin/Calcitonin双受体激动剂（DACRA）。31名健康成人接受单次1–10 mg给药，半衰期约6天；10 mg组6例受试者在Day 24平均体重下降3.3%，CTX-1约下降60%。未见SAE或药物相关停药，但5–10 mg组出现明显剂量相关恶心、呕吐。MAD部分已经启动。 研发看点 这条值得高度关注，因为它提供了口服小分子Amylin路线罕见的首次人体药效信号。3.3%的单次给药后减重非常亮眼，但样本只有6例，而且高剂量GI耐受性已经出现，需要等待MAD数据判断真实治疗窗。 来源：Structure Therapeutics SEC 8-K https://www.sec.gov/Archives/edgar/data/1888886/000110465926105688/tm2624945d1_8k.htm 03｜BEAM-302：AATD体内碱基编辑最长随访18个月 Beam Therapeutics在ERS 2026更新BEAM-302Ⅰ/Ⅱ期数据。该药通过LNP递送腺嘌呤碱基编辑器，在体内纠正SERPINA1 PiZ突变。29例单次给药患者中，60 mg组总AAT稳定升至约13.5–14.4 μM，超过11 μM保护阈值；校正后的M-AAT约占总AAT93%，突变Z-AAT下降84%。最长随访达18个月，疗效指标保持稳定。 研发看点 BEAM-302再次验证了“一次LNP给药→体内修复致病突变→长期恢复功能蛋白”的可行性。更重要的是，其全球关键队列已经开始给药，项目已经从早期PoC逐步进入注册开发。 来源：Beam Therapeutics官方公告 https://investors.beamtx.com/news-releases/news-release-details/beam-therapeutics-presents-updated-clinical-data-phase-12-trial 04｜BMS arlo-cel：GPRC5D CAR-T注册性Ⅱ期达到主要终点 Bristol Myers Squibb公布arlocabtagene autoleucel（arlo-cel，BMS-986393）注册性Ⅱ期QUINTESSENTIAL顶线结果。该产品是一款自体GPRC5D CAR-T，用于四类药物暴露、既往接受过BCMA靶向治疗的复发/难治多发性骨髓瘤。研究达到主要终点，ORR具有统计学和临床意义，同时达到完全缓解率（CRR）等关键次要终点；完整结果将在后续学术会议发布。 研发看点 其战略价值在于绕开BCMA耐药。GPRC5D表达相对独立于BCMA，因此对于已经接受BCMA CAR-T、ADC或双抗的患者仍可能有效。如果完整数据中的DoR和安全性足够有竞争力，arlo-cel有机会形成多发性骨髓瘤“BCMA之后”的重要CAR-T治疗路径。 来源：Bristol Myers Squibb官方公告 https://news.bms.com/news/corporate-financial/2026/Bristol-Myers-Squibb-Announces-Positive-Topline-Results-from-Registrational-Phase-2-QUINTESSENTIAL-Trial-of-the-Potential-First-in-Class-GPRC5D-Directed-CAR-T-Cell-Therapy-Arlocabtagene-Autoleucel----/default.aspx 05｜近期重点｜NouvSight001：睿健医药中美IND双报双批 睿健医药宣布通用型、现货型光感受器细胞治疗产品NouvSight001注射液获得中美两地临床许可，用于视网膜色素变性（RP）。中国NMPA批准开展I/III期联合临床研究，美国FDA批准I/II期海外联合临床研究，并给予特别豁免权（Special Exemption）。NouvSight001基于睿健“AI+化学诱导（AI+Chem）”平台开发，作为细胞替代疗法，不依赖特定致病基因型。 研发看点 这条事件的价值不仅在于一个眼科细胞治疗项目进入临床，更在于其验证了睿健“one platform, multiple products, global development”的复制能力。继帕金森病NouvNeu001中美同步推进后，NouvSight001将同一底层平台拓展到视网膜退行性疾病，进一步验证通用现货型细胞产品在CMC、全球监管和跨区域临床执行上的可复制性。 来源：睿健医药官方信息 https://cn.iregene.com/ 06｜X4 mavorixafor：FDA同意缩减Ⅲ期样本量，注册路径进一步明确 X4 Pharmaceuticals宣布与FDA完成Type C会议，FDA同意将mavorixafor治疗慢性中性粒细胞减少症的全球Ⅲ期4WARD研究样本量从176例降至126例，同时认为调整后仍能维持两个共同主要终点——年化感染率下降及ANC应答——所需的统计效能。FDA还认为公司拟议的安全性数据库可支持潜在sNDA。 研发看点 这不是疗效数据，但属于直接影响注册性Ⅲ期执行效率的重要监管决定。样本量减少约28%，意味着开发成本和入组压力明显降低，同时FDA原则上认可安全数据库框架。不过FDA会议反馈并不构成最终批准承诺，真正决定项目价值的仍是4WARD在感染率这一临床终点上的结果。 来源：X4 Pharmaceuticals官方公告 https://investors.x4pharma.com/node/12501/pdf 今日最值得继续跟踪的3个项目 del-desiran 下一节点：完整HARBOR数据及Novartis开发决策 核心问题：是机制失败，还是临床终点无法捕捉真实获益？ ACCG-2671 下一节点：Ⅰ/Ⅱa期MAD数据 核心问题：多次给药后能否复制减重信号，同时把恶心、呕吐控制在可接受范围？ BEAM-302 下一节点：全球关键队列及更长期数据 核心问题：AAT恢复能否真正进一步转化为肺和肝脏临床获益？ PharmaRadar｜研发速递

- FDA Agrees to Reduced Sample Size for the Global 4WARD Phase 3 Chronic Neutropenia Trial - - Expect Completion of Enrollment by Year-End 2026 and Topline Data in H1 2028 - BOSTON, Sept. 08, 2026 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company focused on improving the lives of people with rare hematology diseases, today announced the positive outcome of its Type C Meeting with the U.S. Food and Drug Administration (FDA) related to the global 4WARD Phase 3 clinical trial. The purpose of the meeting was to gain alignment on a revised sample size and associated statistical power and the size of the safety database to support a supplemental new drug application (sNDA) for mavorixafor for the treatment of chronic neutropenia in 4WARD. The FDA agreed with the Company’s analysis that the reduction in sample size for the 4WARD trial from 176 to 126 participants maintains adequate overall power for the co-primary endpoints of the reduction in annualized infection rate and positive absolute neutrophil count (ANC) response. In addition, the FDA indicated that the proposed safety database would be acceptable to support a potential sNDA. ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); “After a rigorous re-examination of the statistical plan for 4WARD, we determined that the trial was overpowered and that we could reduce the sample size to 126 participants while preserving good statistical power for our co-primary endpoints,” said Adam Craig, M.D., Ph.D., Executive Chairman of X4 Pharmaceuticals. “We are pleased that the FDA agreed with our analysis. With continued execution from our new Clinical Research Organization (CRO), we expect to complete the enrollment of 4WARD by the end of this year and report topline data in the first half of 2028.” “With an estimated 15,000 patients experiencing serious and/or recurring infections as a result of their chronic neutropenia, we continue to believe mavorixafor can address a significant market opportunity based on its unique value proposition for the treatment of this rare disease with very limited therapy options,” concluded Dr. Craig. About the 4WARD Clinical Trial The 4WARD trial is a global, pivotal Phase 3 clinical trial evaluating the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without G-CSF) in patients with congenital, acquired primary autoimmune, or idiopathic chronic neutropenia who are experiencing recurrent and/or serious infections. The 52-week trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 126 patients aged 12 years and older with confirmed trough absolute neutrophil count (ANC) levels less than 1,000 cells per microliter at baseline screening and histories of two or more serious and/or recurrent infections in the prior year. The co-primary endpoints of the study are the reduction in annualized infection rate and positive absolute neutrophil count (ANC) response. For more information, visit clinicaltrials.gov (NCT06056297) . ezstandalone.cmd.push(function () { ezstandalone.showAds(132); }); About Chronic Neutropenia and Mavorixafor Chronic neutropenia is a primary, rare blood condition characterized by abnormally low levels of circulating neutrophils in the blood lasting more than three months, persistently or intermittently. As a result, people with chronic neutropenia are at an increased risk of serious and life-threatening infections and reduced quality of life. Neutrophils are retained in the bone marrow by the CXCR4/CXCL12 axis, creating a reserve of cells. Mavorixafor is a small molecule delivered in a capsule for oral dosing as a selective antagonist of the chemokine receptor, CXCR4. Down-regulation of the CXCR4 receptor by mavorixafor has been shown to mobilize functional neutrophils from the bone marrow into the peripheral bloodstream across multiple disease states. The level of circulating neutrophils is typically determined by the absolute neutrophil count (ANC) obtained from a blood draw. About X4 Pharmaceuticals X4 Pharmaceuticals is a company focused on improving the lives of people with rare hematology diseases by developing and commercializing innovative therapies in areas with significant unmet needs. Leveraging expertise in diseases of the immune system and CXCR4 biology, X4 has successfully developed mavorixafor, an orally available CXCR4 antagonist that is commercially available in the U.S. as XOLREMDI® in its first indication. The Company is currently conducting a global, pivotal Phase 3 clinical trial (4WARD) evaluating mavorixafor in chronic neutropenic disorders. The U.S. FDA has granted Fast Track designation to mavorixafor for the treatment of chronic neutropenia. X4 is headquartered in Boston, Massachusetts. For more information, please visit . ezstandalone.cmd.push(function () { ezstandalone.showAds(133); }); X4 Forward Looking Statements This press release contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by the words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target,” or other similar terms or expressions that concern X4’s expectations, strategy, plans, or intentions. Forward-looking statements include, without limitation, implied or express statements regarding the Company’s ability to obtain and maintain regulatory approval for its product candidates, plans for the commercialization of XOLREMDI in the European Union by Norgine, the potential achievement of milestones and receipt of royalties under the Company’s licensing and supply agreement with Norgine, the expected design and enrollment of the Company’s clinical trials, including expected timing for full enrollment in 4WARD, the sufficiency of the Company’s cash resources and its expected cash runway, and future plans for the Company. Any forward-looking statements in this press release are based on management’s current expectations and beliefs. These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond X4’s control, which could cause actual results to differ materially from those contemplated in these forward-looking statements, including the risks that even if approved, mavorixafor may not ultimately be commercially successful; the Company is unable to initiate and complete its clinical trials, including the 4WARD trial; the FDA’s feedback provided in connection with the Type C meeting is not binding on the FDA and the FDA may take a different position in connection with its review of any sNDA; the reduced sample size may adversely affect the ability of the 4WARD trial to demonstrate statistically significant results with respect to its co-primary endpoints; enrollment in the 4WARD trial may not be completed within the timeframe described in this press release, or at all; and other risks and uncertainties, including those described in the section entitled “Risk Factors” in X4’s most recent Annual Report on Form 10-K, as well as in other filings X4 makes with the Securities and Exchange Commission, including its Quarterly Reports on Form 10-Q, from time to time. X4 undertakes no obligation to update the information contained in this press release to reflect new events or circumstances, except as required by law. X4 Investor Contact: Remy Bernarda Jenny Kobin IR Advisory Solutions IR@X4pharma.com Source: X4 Pharmaceuticals, Inc. ezstandalone.cmd.push(function () { ezstandalone.showAds(134); });