Intervertebral Disc Degeneration

Japan-based Seikagaku will face an FDA advisory committee on Friday, with the agency raising concerns ahead of the meeting regarding the efficacy of its condoliase injection for the treatment of radicular leg pain associated with lumbar disc herniation in adults. Ahead of the meeting of the Anesthetic and Analgesic Drug Products Advisory Committee, the FDA notes that one of the clinical trials failed on its primary endpoint. Overall, the agency sounded positive on an approval, noting in briefing documents released Wednesday that “the negative study may inform the benefit-risk assessment for specific populations who may be considered for treatment with condoliase if the product is approved.” One of the three clinical trials evaluated by the FDA did not meet its primary efficacy endpoint (change in worst leg pain from baseline to week 13), nor did it meet either of its two key secondary endpoints, including a pain outcome assessment after a year. The change from worst leg pain from baseline to week 52 slightly favored the control in the failed study, FDA said, but the difference was not statistically significant. The agency also noted that the study that failed likely did so because herniation resulting in symptomatic nerve impingement was not present in most of the patients enrolled, and that’s what the injection targets. The agency said that Seikagaku “performed a detailed analysis to explain the negative U.S. findings despite the positive findings in Study 1031 in Japan.” The company highlighted two key issues: 1) A majority of patients in the failed trial did not have definitive impingement of the nerve root by the disc herniation on an MRI. 2) Baseline back pain was significantly higher in the US study compared to the study in Japan. Two other Phase 3 clinical trials were positive, although one was conducted exclusively in Japan. And in both trials, nerve impingement conducive to condoliase treatment was confirmed by imaging, FDA said. Friday’s committee will have an up-or-down vote on the injection, with the question presented as, “Do the benefits of condoliase injection for treatment of radicular leg pain associated with confirmed nerve root impingement caused by lumbar disc herniation in adults with radicular leg pain outweigh the risks?” Seikagaku, which also markets an intra-articular injection for the treatment of knee osteoarthritis in the US, calls its condoliase injection an improvement on the current treatment landscape, because it does not require general anesthesia and is “less invasive to the patient than surgical treatment.”

NEW YORK--( BUSINESS WIRE )--Spine BioPharma, Inc., a development stage company committed to non-opiate, non-surgical therapies for Degenerative Disc Disease (DDD), today announced that Chief Executive Officer Marc Viscogliosi will present a corporate overview and update at Biotech Showcase 2025, taking place in San Francisco January 13-15. Biotech Showcase 2025 Presentation Details Date: Tuesday, January 14, 2025 Time: 3:00 PM PT Venue: Hilton San Francisco Union Square Hotel, San Francisco, CA (United States) Room: Franciscan-B About SB-01 For Injection SB-01 is a 7-amino acid synthetic peptide that binds to and antagonizes TGF-Beta activity. TGF-Beta is a pleiotropic cytokine expressed by almost every tissue and cell type, is stored in abundance in the extracellular matrix, and possesses suppressive and stimulatory signaling pathways. In many diseases, there are high concentrations of TGF-Beta that result in a spectrum of negative downstream effects including inflammation, fibrosis, neoinnervation, hyperexcitability of nerves and cell proliferation. SB-01 modulates TGF-Beta concentration, without eliminating it, mitigating the negative downstream effects. About Spine BioPharma Spine BioPharma is committed to developing non-opiate, non-surgical treatments that will reduce pain, restore function, and slow or stop pathological disease progression. Spine BioPharma’s lead candidate, SB-01 For Injection, is a first-in-class treatment of DDD, offering potential clinical benefits of pain relief, restoration of function, and prevention of disease progression. To learn more about Spine BioPharma, visit www.spinebiopharma.com

*仅供医学专业人士阅读参考 今天早上一起来，北京温度突然降了不少，不过天倒是挺蓝的。往年一到冬天就开始忧心雾霾问题，这几年的整治还是蛮有效果，体感上好天气是越来越多了。 除了雾霾的主要污染源PM2.5，其实还有更多造成空气污染的成分，比如主要由交通工具燃油燃烧产生的二氧化氮（NO2），也是要为一系列疾病负起责任。 近期，北京大学、复旦大学、西安交通大学、牛津大学的联合科研团队在《柳叶刀·公共卫生》杂志发文，研究者们分析了来自中国嘉道理生物库的50余万中国人数据，发现长期二氧化氮暴露与多种疾病高风险存在正向关联。 二氧化氮年暴露量每升高10 μg/m³，分别与心血管疾病、呼吸道疾病、肌肉骨骼病、精神行为障碍发生风险升高4%、3%、11%、12%有关。 论文题图 不得不说，相较PM2.5，二氧化氮的危害程度在人们心中是低不少的。就看《全球疾病、伤害和风险因素负担研究》（GBD），PM2.5被列为全球疾病负担的主要贡献者，而二氧化氮只被认为是哮喘的可归因因素。 那么事实如何呢？ 研究者们调取了最大规模的中国人队列嘉道理生物库，结合卫星记录、气象参数、人口分布和道路网格等数据，将二氧化氮浓度的分析精度定位到了1km × 1km的小地块，并对二氧化氮暴露和参与者的医疗数据进行匹配分析。 最终纳入分析的有512709名参与者，中位基线年龄52岁，59%为女性，44.1%为城市居民。参与者在2005年-2008年期间的年平均二氧化氮暴露量，第一四分位数为19 μg/m³，第四分位数为41.1 μg/m³，超过99.96%的参与者暴露量高于10 μg/m³。 分析结果显示，二氧化氮暴露量较高的参与者往往居住在城市地区，家庭收入较高，有饮酒习惯，使用清洁燃料，同时PM2.5暴露量也更高。 在嘉道理生物库的10个调查地点之间，二氧化氮暴露水平差异挺大，不过总的来说，二氧化氮暴露在2005年-2013年之间有一个显著的增加，随后略有下降，在整个随访期间二氧化氮水平是上升的。 不同地点的年二氧化氮暴露 在所有疾病大类中，二氧化氮暴露与精神行为障碍、心血管、呼吸和肌肉骨骼病之间存在显著的关联，调整PM2.5后正向关联性更明显。 二氧化氮与疾病大类的关系 研究者进一步分析了12种特定的疾病，发现二氧化氮与高血压、下呼吸道感染、关节病、脊椎病、椎间盘疾病、缺血性心脏病、缺血性卒中和哮喘存在正相关。 二氧化氮与12种特定疾病的关系 此外，分析发现，精神行为障碍中，男性参与者的相关性较女性更强，而女性参与者与肌肉骨骼病的相关性更强。 从机制上来说，二氧化氮是一种反应性气体，可被呼吸道上皮吸收，产生活性氮/活性氧/氧化脂质分子，从而增加局部和全身的炎症、促进氧化应激。这可能导致呼吸免疫功能受损和动脉粥样硬化、高血压风险增加，这都是心肺疾病的风险因素。全身炎症可能引起自身免疫反应，与肌肉骨骼病风险增加有关。此外，二氧化氮还参与激素调节和内分泌紊乱，可能与精神行为障碍、肌肉骨骼病和内分泌疾病风险的升高有关。 参考资料： [1]Xia X, Meng X, Liu C, Guo Y, Li X, Niu Y, Lam KBH, Wright N, Kartsonaki C, Chen Y, Yang L, Du H, Yu C, Sun D, Lv J, Chen J, Yang X, Gao R, Wu S, Kan H, Chan KH, Li L, Chen Z; China Kadoorie Biobank Study Group. Associations of long-term nitrogen dioxide exposure with a wide spectrum of diseases: a prospective cohort study of 0·5 million Chinese adults. Lancet Public Health. 2024 Dec;9(12):e1047-e1058. doi: 10.1016/S2468-2667(24)00264-0. PMID: 39643329; PMCID: PMC11626078. 本文作者丨代丝雨