Epidermal Nevus

Once-daily topical treatment of target cutaneous neurofibromas (cNFs) with NFX‑179 Gel 1.5% achieved statistically significant reduction in size First randomized, double-blind, vehicle-controlled Phase 2b clinical trial to report positive results in the treatment of cutaneous neurofibromas Multiple secondary endpoints met; significant reductions in the volume and height of cNFs correlates with patient-reported meaningful improvement in their cNFs Efficacy and tolerability results support advancing NFX‑179 Gel program to Phase 3 development in 2024 BOSTON, Nov. 13, 2023 /PRNewswire/ -- NFlection Therapeutics Inc., a company developing topical MEK inhibitors for RAS-mediated skin conditions, today announced positive topline results from a randomized, double-blind, vehicle-controlled Phase 2b clinical trial (NCT05005845) evaluating NFX‑179 Gel as a treatment for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1), a rare genetic condition. Cutaneous neurofibromas appear in over 95% of people with NF1 and are physically disfiguring, painful, cause extensive psychological harm, and negatively impact quality of life. There are currently no FDA-approved therapeutics for the treatment of cNFs. The Phase 2b study was a 6‑month double-blind, randomized, vehicle-controlled study of 199 subjects to determine the safety and effectiveness of NFX‑179 Gel 0.5% and 1.5% compared with vehicle in patients with cNFs. The study was conducted at 24 investigational centers in the U.S. NFX‑179 Gel was applied topically to target cNF tumors for six months, enabling delivery of high concentrations of NFX‑179 to the tumors. The highest concentration of NFX‑179 tested, 1.5%, achieved the study's primary efficacy endpoint, with a statistically significant improvement over vehicle in the shrinkage of cNFs in people with NF1 that was highly correlated with patient-reported meaningful improvements in their cNFs. Consistent with its design as a soft, or metabolically labile, MEK inhibitor, NFX‑179 Gel was generally well tolerated, and plasma drug concentrations were orders of magnitude lower than those typically observed for oral MEK inhibitors. "Cutaneous neurofibromas, which present in over 95 percent of people with NF1, are associated with significant psychosocial impact and are often the most burdensome symptom of the condition," said study investigator Miriam Bornhorst, MD, Assistant Professor of Pediatrics, and the Clinical Director of the Gilbert Family Neurofibromatosis Institute at Children's National Hospital. "The data shows that NFX‑179 Gel significantly reduced the size of cNFs across multiple efficacy endpoints and was generally well tolerated. We are excited to see the potential for NFX‑179 Gel as the first topical therapy for the treatment of cNFs in people with NF1." The primary efficacy endpoint of the study was a subject-level responder analysis, with a response defined as at least 50% reduction in cNF volume above the surrounding non-tumor skin for five or more of the ten treated tumors, after 6 months of once-daily application of NFX‑179 Gel. The study met the primary efficacy endpoint with dose-dependent responder rates of 44.2% with NFX‑179 Gel 1.5%, 34.8% with NFX‑179 Gel 0.5%, and 24.1% with vehicle. The high dose had a statistically significant higher responder rate than vehicle (p = 0.03). "We are pleased to report success from our Phase 2b NF1 patient trial that supports the first-in-class potential of NFX‑179," said William Hodder, Chief Executive Officer of NFlection. "Based on the favorable efficacy and tolerability profile NFX‑179 Gel demonstrated in this study, we plan to meet with U.S. and European regulators and move the program to Phase 3 development in 2024. We would like to thank the patients, our investigators and collaborators, including The Children's Tumor Foundation, who made this study possible. We look forward to continuing the development of this important therapy for the NF1 community." "In addition to developing efficient preclinical and clinical neurofibromatosis (NF) test platforms, CTF is dedicated to investing in new medicines for people with NF. Our support for NFlection demonstrates that commitment," said Annette Bakker, PhD, President of The Children's Tumor Foundation. "People with NF1 with cutaneous neurofibromas have been overlooked for a long time and are desperate for safe and easy-to-apply treatment options." About NFX‑179 Topical Gel NFX‑179 is an investigational mitogen-activated protein kinase kinase (MEK) inhibitor. NFX‑179 is a "soft" (metabolically labile) drug, which, when formulated as NFX‑179 Gel for topical application, is designed to concentrate at the dermal site of action but degrade in systemic circulation, thereby significantly reducing side effects routinely seen with systemically available MEK inhibitors. NFlection is developing NFX‑179 Gel for the treatment of cutaneous neurofibromas in people with neurofibromatosis type 1 and has received Orphan Designation in the United States and European Union for this indication. About NFlection Therapeutics Inc. NFlection is a clinical-stage biopharmaceutical company focused on the development of novel therapies to address the needs of patients with neurofibromatosis type 1, immunosuppressant-mediated squamous cell carcinoma, and congenital birthmarks such as keratinocytic epidermal nevi and nevi sebacei. To address these RAS-mediated disorders driven by the aberrant activation of the Ras/Raf/MEK/ERK pathway, we are developing first-in-class MEK (mitogen-activated protein kinase kinase) inhibitors for topical treatment of these conditions. To learn more about the company, please visit . SOURCE NFlection Therapeutics

4月6日，诺华（Novartis）宣布，美国FDA加速批准Vijoice（alpelisib）上市，用于治疗需要接受系统治疗的PIK3CA相关过度生长疾病谱系（PROS）成人和2岁及以上儿童患者。他们表现出严重的症状。新闻稿指出，Vijoice是美国FDA批准的首个PROS治疗药物，针对特定患者的PROS疾病根本原因。 PROS泛指因PIK3CA基因突变所致病谱系，特征为血管、淋巴系统和其他组织非典型过度生长和异常，估计影响14人/100万人。与PROS相关的特异性疾病包括CLOVES综合征（丁香综合征）、巨指症、肌肉性HH和表皮痣、良性苔藓样角化病或脂溢性角化病等。PROS疾病可影响生活质量，并对患者及其家庭构成一系列身体、情绪和社会挑战，范围从功能影响和发育迟缓至慢性疼痛、运动问题和孤独感。PROS管理可能具有挑战性，需要多学科团队的合作，患者和医生只能获得专注于症状管理的干预措施。 美国FDA的批准基于EPIK-P1的真实世界证据，EPIK-P1是一项回顾性、非干预性病历研究，研究显示接受Vijoice治疗的患者出现了靶病灶体积减小和PROS相关症状的改善。在第24周进行的主要终点分析显示，27%的患者（10/37）达到确认的治疗缓解，定义为PROS靶病灶体积总和减少20%以上。在基线和第24周进行影像学检查的患者中，近四分之三（74%，23/31）患者显示靶病灶体积有所缩小，平均缩小13.7%，在主要分析时无患者发生疾病进展。 此外，在第24周，研究者观察到患者的疼痛（90%，20/22）、疲乏（76%，32/42）、血管畸形（79%，30/38）、肢体不对称（69%，20/29）和弥散性血管内凝血（55%，16/29）较基线获得改善。 患者组织CLOVES综合征社区（CLOVES Syndrom Community）执行主任Kristen Davis女士表示：“今天PROS的首个治疗药物获批，为受这些罕见病症影响的患者和家庭提供了更好生活质量的希望。PROS状况可能使人衰弱和致残，并可能导致日常活动中断。直到今天，患者的唯一治疗选择往往是手术或介入放射学手术。” 诺华美国创新药部门总裁Victor Bulto先生表示：“Vijoice的获批标志着患者的一个转折点，直到现在，这些患者还没有一种获批的疗法来专门解决他们的疾病，我们感谢参与EPIK-P1试验的医生、患者和家属。我们正在继续投资研究，以推进对PROS状况的科学理解，并了解Vijoice的全部潜力。” 参考来源： [1] FDA approves Novartis Vijoice® (alpelisib) as first and only treatment for select patients with PIK3CA-Related Overgrowth Spectrum (PROS). Retrieved 2022-04-06, from https://www.globenewswire.com/news-release/2022/04/06/2417163/0/en/FDA-approves-Novartis-Vijoice-alpelisib-as-first-and-only-treatment-for-select-patients-with-PIK3CA-Related-Overgrowth-Spectrum-PROS.html 内容来源于网络，如有侵权，请联系删除，谢谢。