Ponsegromab

▎药明康德内容团队编辑 FDA颁发首个治疗软骨发育不全的突破性疗法认定 BridgeBio Pharma今日宣布，其正在开发的口服药物infigratinib已获得美国FDA授予的突破性疗法认定，用于治疗患有软骨发育不全的儿童患者。新闻稿指出，这是FDA为治疗软骨发育不全的在研疗法颁发的首个突破性疗法认定。 该突破性疗法认定的授予基于2期临床试验PROPEL 2的初步临床证据。在PROPEL 2试验的第5队列（0.25 mg/kg/天）中，口服infigratinib治疗导致患者年化身高增长速度（AHV）显著且持续增加。在12个月时，患儿的AHV相对于基线的平均增长为+2.51厘米/年，在18个月时为+2.50厘米/年，增长持续且具有统计学意义（p=0.0015）。 软骨发育不全发病的背后病理机制是由于编码成纤维细胞生长因子受体3（FGFR3）的基因出现突变，导致FGFR3蛋白过度活跃。FGFR3是骨骼发育的负向调节分子，可影响软骨细胞的增殖和分化。而infigratinib通过阻断FGFR3的活性，就好像松开抑制儿童生长的“刹车”，直接靶向软骨发育不全的潜在病理生理学，从而促进软骨形成，让患儿的生长速率恢复正常。 辉瑞抗GDF-15抗体达到2期临床终点，显著改善癌症患者体重 辉瑞日前宣布，在治疗癌症恶病质（cachexia）患者的2期临床研究中，靶向生长分化因子-15（GDF-15）的单克隆抗体ponsegromab达到主要终点。研究结果显示，在GDF-15水平升高的癌症恶病质患者中，ponsegromab显著改善了患者体重。恶病质是一种常见的、危及生命的消耗性疾病，导致体重下降和功能衰退，严重影响癌症患者的生活质量。研究结果已经在《新英格兰医学杂志》上发表。基于这一积极结果，辉瑞将在2025年启动注册性研究。 这项2期临床试验共纳入了187名患有非小细胞肺癌、胰腺癌或结直肠癌的参与者。在所有剂量组中，接受ponsegromab治疗的患者在12周内体重显著增加：100 mg治疗组体重增加2.02%（95% CI，-0.97%-5.01%），200 mg组体重增加3.48%（95% CI，0.54%-6.42%），400 mg组体重增加5.61%（95% CI，2.56-8.67%）。与安慰剂相比。在400 mg组中，评估恶病质的多个指标，包括食欲、恶病质症状、身体活动和骨骼肌指数均有所改善。Ponsegromab的使用未发现临床显著的不良趋势。服用安慰剂的患者中8.9%出现治疗相关不良事件，而服用ponsegromab的患者中这一数值为7.7%。 治疗广泛神经系统疾病，新锐完成6800万美元A轮融资 Nura Bio今日宣布完成6800万美元的A轮扩展融资，将A轮融资总额提升到1.4亿美元。此次融资由创始投资者The Column Group领投，现有投资者Samsara Bio Capital和Euclidean Capital以及新投资者Sanofi Ventures参与。 该公司的主打在研疗法NB-4746是一款具有脑渗透性的SARM1抑制剂。SARM1是一种富集于神经元的烟酰胺腺嘌呤二核苷酸（NAD）水解酶，已被证明是重要的轴突内在代谢传感器及轴突退化的核心驱动因素。轴突退化是多种神经系统疾病的早期标志。早期阻止轴突退化能够提供结构和功能上的神经保护，在多种神经系统疾病的治疗中具有巨大潜力。临床前研究支持NB-4746在中枢、外周和眼神经系统疾病中提供广泛的轴突保护和功能改善的潜力。目前，NB-4746已在健康志愿者中进行的1期临床试验中取得成功。Nura Bio计划于2025年在患者群体中启动1b/2期临床试验。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] Pfizer Presents Positive Data from Phase 2 Study of Ponsegromab in Patients with Cancer Cachexia. Retrieved September 17, 2024, from https://www.pfizer.com/news/press-release/press-release-detail/pfizer-presents-positive-data-phase-2-study-ponsegromab [2] Nura Bio Closes Series A Financing with $68 Million in New Funds, Bringing Total Raised to $140+ Million. Retrieved September 17, 2024, from https://www.businesswire.com/news/home/20240917107266/en/Nura-Bio-Closes-Series-A-Financing-with-68-Million-in-New-Funds-Bringing-Total-Raised-to-140-Million [3] BridgeBio Announces Infigratinib Is the First Ever Investigational Therapeutic Option for Achondroplasia to Be Awarded Breakthrough Therapy Designation by the FDA. Retrieved September 17, 2024, from https://www.globenewswire.com/news-release/2024/09/17/2947311/0/en/BridgeBio-Announces-Infigratinib-Is-the-First-Ever-Investigational-Therapeutic-Option-for-Achondroplasia-to-Be-Awarded-Breakthrough-Therapy-Designation-by-the-FDA.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。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：本文来自药明康德内容团队，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

BARCELONA — One of this weekend’s sleeper data presentations at Europe’s biggest oncology conference puts Pfizer in a leading position in a common cancer condition with no approved treatments in the US or Europe. The New York-based pharma giant’s GDF-15-directed monoclonal antibody helped cancer patients gain weight and, at the highest dose, experience improvements in appetite, physical activity and muscle mass in a Phase 2 trial, according to data presented at the European Society for Medical Oncology confab on Saturday. Analysts at Leerink Partners think the experimental medicine, code-named ponsegromab, has blockbuster potential. But the large pharma has many questions to work through before it can mount a registrational study next year for ponsegromab in cancer cachexia, a muscle-wasting condition that leads to severe weight loss and impacts a patient’s ability to tolerate cancer medications. Patients with cachexia also require more healthcare resources, leading to a “high clinical and economic burden,” according to another Pfizer-funded study presented at ESMO. Doctors have long sought a treatment for the metabolic condition, which some research suggests may be linked to up to 30% of cancer deaths. It’s also a strain on patients with chronic conditions like heart failure and chronic obstructive pulmonary disease, among others. The broad potential gives ponsegromab a shot at achieving sales of $1 billion or more, Leerink Partners analyst David Risinger wrote in a Sunday evening note. Despite its prevalence, though, the condition has not received “the attention it deserves,” Min Li, a professor and co-leader of the cancer biology program at the Stephenson Cancer Center in Oklahoma, said in an email. “We are now more confident in saying that we can see the light at the end of the tunnel,” Li said in the days after the ESMO presentation and simultaneous publication of the Phase 2 data in the New England Journal of Medicine . Having one of the world’s biggest pharma companies with ample R&D resources to approach late-stage testing could be a boon for the field. “Incredible progress is finally being made in this space, and we very much hope that Pfizer’s findings continue to be positive and pave the way for more successful trials to follow,” Andy Judge, a University of Florida professor and president of the Cancer Cachexia Society, told Endpoints in an email. Cachexia comes with a lot of complexities, likely leading to a challenging Phase 3 showdown for Pfizer. The company anticipates launching the trial next year and it still needs to hash out plans with regulators, according to a spokesperson, who said Pfizer will share more Phase 3 details at a later date. The condition is quite heterogeneous and impacts different cancers at varying rates, which could make it difficult to prove a treatment works in late-stage trials. Li noted that “there is no consensus on the optimal endpoint to evaluate cancer cachexia.” Another biotech, NGM Bio, warned in recent years of the lack of a clear regulatory path for cachexia. Another company received approval in Japan in 2020 for the medicine anamorelin, but the ghrelin receptor agonist was rejected in Europe a few years before. Also standing in the way is the number of organs and tissues involved in the systemic dysfunction. Going after a single pathway “has yielded limited efficacy,” Li said. Pfizer’s ponsegromab goes after growth differentiation factor 15, or GDF-15. The company’s researchers have said neutralizing GDF-15 could lead to improvements in caloric intake and boost physical activity. The candidate was discovered in-house and first entered the clinic in a 2018 healthy volunteer trial. Ponsegromab is also being tested in patients with heart failure . That study is enrolling patients with cardiac cachexia or fatigue in its main cohort and is expected to be completed next March, according to the federal trials database. Li noted other potential pathways in cancer cachexia could be targeted, such as “myostatin/activin signaling, IL-6, ghrelin, circular RNAs, metabolic enzymes, TNF and TGF.” Meanwhile, more studies are needed to “directly prove” that stabilizing muscle and fat reserves, “or even revers[ing] those losses,” has a direct impact on patient outcomes, Michael Rosenthal, assistant director of radiology at Dana-Farber/Brigham and Women’s Hospital, said in an email. Aside from the effects on weight, doctors will look for impacts on daily activities. “It would be impressive to see improvement in ECOG performance status and overall survival in a randomized trial of chemotherapy with or without ponsegromab,” Vincent Chung, a medical oncologist at City of Hope, said in an email. ECOG is a scale that assesses a patient’s ability to function, including walking and self-care activities. Pfizer is in the lead in cachexia drug development, and it’s no stranger to breaking open fields, having done so in areas like ATTR-CM, where it could soon face competition. Other drugmakers looking at cachexia include UK-based Actimed Therapeutics, Tokyo-based TMS and Vistagen, which says on its website that it is “evaluating the path forward” for its candidate for more Phase 2 development. Even if those medicines make it to market, it’s still important to think about treating cachexia in a “multi-dimensional way, rather than a single drug,” David Hui, director of supportive and palliative care research at the University of Texas MD Anderson Cancer Center, said in an interview on the sidelines of ESMO. Doctors currently work with a team of healthcare professionals to address cachexia with diet and exercise and medications to treat symptoms of pain, difficulty swallowing and other complications, he said. “Having the dietitian, physical therapy and supportive palliative care team working side by side together with the patient and family can, hopefully, lead to improved outcomes because everyone may have different concerns related to cachexia,” Hui said.