Tonix Pharmaceuticals Presented Data and Analyses of TNX-102 SL Treatment Effects on Fibromyalgia at the 2024 Military Health System Research Symposium (MHSRS)
August 28, 2024 7:00am EDT Download as PDF
Oral presentation highlighted results from confirmatory Phase 3 RESILIENT study of TNX-102 SL (sublingual cyclobenzaprine HCl) treatment demonstrating statistically significant improvement in primary endpoint of fibromyalgia nociplastic pain and in all six key secondary endpoints, including sleep quality
NDA submission on track for second half 2024; Fast Track designation granted by FDA; FDA decision expected 2025
TNX-102 SL is a potential non-opiod analgesic targeting non-restorative sleep in fibromyalgia: Post hoc analyses highlight strong correlations between improvements in nociplastic pain and sleep quality
Nociplastic pain originates from altered pain perception in the brain and is the type of pain that manifests in fibromyalgia and other chronic overlapping pain conditions (COPCs)
CHATHAM, N.J., Aug. 28, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, presented data in an oral presentation at the 2024 Military Health System Research Symposium (MHSRS), held August 26-29, 2024, in Kissimmee, Fla. A copy of the Company's presentation, titled "Assuaging Agony: Novel Pain Therapeutics", is available under the Scientific Presentations tab of the Tonix website at .
In the Phase 3 RESILIENT study, TNX-102 SL met the pre-specified primary endpoint of significantly reducing daily pain compared to placebo (p-value=0.00005) in participants with fibromyalgia. TNX-102 SL demonstrated broad syndromal benefits with statistically significant improvement in all six pre-specified key secondary endpoints including those related to improving sleep quality, reducing fatigue, and improving patient global ratings and overall fibromyalgia symptoms and function. A post hoc analysis showed strong correlations between improvements in pain and sleep quality at Week 14, supporting the concept that targeting sleep quality has the potential to achieve syndromal improvement in fibromyalgia. TNX-102 SL was well tolerated with an adverse event profile comparable to prior studies and no new safety signals observed.
"Traditional analgesics like NSAIDs or opioids often prove ineffective, if not deleterious, as strategies for treating fibromyalgia," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "In contrast, TNX-102 SL provided broad-spectrum symptom relief in the Phase 3 RESILIENT study and was designed as a bedtime treatment to target non-restorative sleep and improve sleep quality. With the statistically significant results of two positive Phase 3 studies of TNX-102 SL in fibromyalgia we believe TNX-102 SL has the potential to be the first new treatment option for fibromyalgia patients in 15 years."
Dr. Lederman continued, "Fibromyalgia is the prototypic nociplastic syndrome and chronic overlapping pain condition (COPC)3,4,5. Our results in fibromyalgia suggest potential for TNX-102 SL in treating other COPCs like post-concussive syndrome6, in which sleep disturbances correlate with persistence and severity. In addition, we expect to begin enrolling this quarter in a trial of TNX-102 SL for acute stress disorder/acute stress reaction in the immediate aftermath of motor vehicle collision in the U.S. Department of Defense (DoD)-funded Optimizing Acute Stress Reaction Interventions (OASIS) trial conducted by the University of North Carolina under an investigator-initiated investigational new drug (IND) application.
Tonix remains on track to submit a new drug application (NDA) to the FDA in the second half of 2024 for TNX-102 SL for the management of fibromyalgia. A decision on approval is expected in 2025.
1Moldofsky H, et al. Psychosom Med. 1975;37:341-51
2Moldofsky H, Scarisbrick P. Psychosom Med. 1976;38:35-44
3Fitzcharles MA, et al. Lancet. 2021;397:2098-110
4Clauw DJ. Ann Rheum Dis. Published Online First: 2024
5Kaplan CM, et al. Nat Rev Neurol. 2024;20, 347–363
6Kureshi S et al. Healthcare (Basel) 2024 12(3): 289.
About Fibromyalgia
Fibromyalgia is a chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system. Fibromyalgia afflicts more than 10 million adults in the U.S., the majority of whom are women. Symptoms of fibromyalgia include chronic widespread pain, non-restorative sleep, fatigue, and brain fog (or cognitive dysfunction). Other associated symptoms include mood disturbances, including anxiety and depression, headaches, and abdominal pain or cramps. Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products. According to the recent report from the U.S. National Academies of Sciences, fibromyalgia is a diagnosable condition that may also occur in the context of Long COVID
About TNX-102 SL
TNX-102 SL is a centrally acting, non-opioid, non-addictive, bedtime investigational drug. The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed for the management of fibromyalgia. In December 2023, the company announced highly statistically significant and clinically meaningful topline results in RESILIENT, the second pivotal Phase 3 clinical trial of TNX-102 SL for the management of fibromyalgia. In the study, TNX-102 SL met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all six key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first statistically significant Phase 3 trial of TNX-102 SL in fibromyalgia, was completed in December 2020. It met its pre-specified primary endpoint of daily pain reduction compared to placebo (p=0.010) and showed activity in key secondary endpoints. In both pivotal studies, the most common treatment-emergent adverse event was tongue or mouth numbness at the administration site, which was temporally related to dosing, self-limited, never rated as severe, and rarely led to study discontinuation (one participant in each study). TNX-102 SL was recently granted Fast Track Designation by the FDA for the management of fibromyalgia and remains on track to submit an NDA to FDA in the second half of 2024.
About Nociplastic Pain
Nociplastic pain is the third category of pain distinct from nociceptive pain and neuropathic pain. Nociplastic pain is characterized by pain arising from altered nociception despite no evidence of actual or threatened tissue damage causing activation of peripheral nociceptors or somatosensory system disease or lesion. Its underlying pathophysiology involves altered pain processing by the central nervous system (CNS). Nociplastic syndromes, officially recognized by the International Association for the Study of Pain (IASP) in 2017, also include several other chronic overlapping pain conditions: myalgic encephalomyelitis/chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorders, forms of chronic back pain and chronic headache. The pathophysiology of nociplastic pain involves central sensitization (CS), where neurons of the CNS become hyperexcitable, amplifying pain signals. CS can be triggered by peripheral pain stimuli, emotional stress, or other factors, leading to persistent pain despite no peripheral nociceptive input.
Tonix Pharmaceuticals Holding Corp.*
Tonix is a fully-integrated biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix recently announced the U.S. DoD, Defense Threat Reduction Agency (DTRA) awarded it a contract for up to $34 million over five years to develop TNX-4200 small molecule broad-spectrum antiviral agents targeting CD45 for the prevention or treatment of infections to improve the medical readiness of military personnel in biological threat environments. Tonix owns and operates a state-of-the art infectious disease research facility in Frederick, MD. The company also owns a Good Manufacutring Practice (GMP)-capable advanced manufacturing facility in Dartmouth, MA, which was purpose-built to manufacture TNX-801, a potential mpox vaccine, and the GMP suites are ready to be reactivated in case of a national emergency. Tonix's development portfolio is focused on CNS disorders. Tonix's priority is to submit an NDA to the FDA in the second half of 2024 for TNX-102 SL, a product candidate for which two statistically significant Phase 3 studies have been completed for the management of fibromyalgia. The FDA has granted Fast Track designation to TNX-102 SL for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction. Tonix's CNS portfolio includes TNX-1300 (cocaine esterase), a biologic designed to treat cocaine intoxication that has Breakthrough Therapy designation, which is enrolling in a potential pivotal Phase 2 trial. Tonix's immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. Tonix also has product candidates in development in the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace SymTouch (sumatriptan injection) 3 mg and Tosymra (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.
*Tonix's product development candidates are investigational new drugs or biologics and have not been approved for any indication.
Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. All other marks are property of their respective owners.
Source: Tonix Pharmaceuticals Holding Corp.
Released August 28, 2024
tonix pharmaceuticals在2024年军工-半导体健康系统研究研讨会上介绍了TNX-102 SL治疗纤维肌痛的数据和分析
2024年8月28日 上午7:00 EDT 下载为PDF
口头报告重点介绍了TNX-102 SL（舌下环苯甲酸氯倍他索）治疗的第3期确认性RESILIENt研究结果，显示在纤维肌痛的病因疼痛和所有六个关键次要终点中均有统计学上显著的改善，包括睡眠质量
新药申报计划顺利进行，预计2024年下半年完成；FDA授予快速通道认定；预计FDA将于2025年作出决定
TNX-102 SL是一种潜在的非阿片类镇痛药，针对纤维肌痛中的非恢复性睡眠：事后分析突显了病因疼痛改善与睡眠质量的强相关性
痛觉过敏性疼痛起源于大脑中变化的疼痛感知，是纤维肌痛和其他慢性重叠疼痛症状的类型
2024年8月28日，新泽西州CHATHAm市（全球新闻社）--Tonix Pharmaceuticals Holding Corp.（纳斯达克上市代码：TNXP）（Tonix或公司）是一家拥有上市产品和发展候选药物流水线的全面集成生物制品公司，其数据在2024年军事卫生系统研究学术会议（MHSRS）的口头报告中展示，该会议于2024年8月26日至29日在佛罗里达州基西米举行。公司的报告题为“Alleviating Agony: Novel Pain Therapeutics”，可在Tonix网站的科学报告选项卡上找到
在第3期RESILIENt研究中，TNX-102 SL达到了预先指定的主要终点，与安慰剂相比显著减少了每日疼痛（p值=0.00005），适用于纤维肌痛患者。TNX-102 SL表现出广泛的综合效益，所有预先指定的六个关键次要终点均有统计学上显著的改善，包括与改善睡眠质量、减少疲劳、改善患者整体评价和纤维肌痛症状和功能有关的终点。事后分析显示，在第14周的疼痛和睡眠质量改善之间存在显著相关性，支持通过改善睡眠质量来实现纤维肌痛的综合改善的观念。TNX-102 SL的耐受性良好，与之前的研究相当，并未观察到新的安全信号。
“像NSAIDs或阿片类传统止痛药物常常被证实无效，甚至有害，作为处理纤维肌痛的策略，”tonix pharmaceuticals首席执行官Seth Lederman.D.说道。“相反，TNX-102 SL在第3期RESILIENt研究中提供了广谱症状缓解，并被设计为针对非恢复性睡眠和改善睡眠质量的床前治疗。通过在纤维肌痛中进行两项积极的第3期研究，显示了统计学显著的结果，我们相信TNX-102 SL有潜力成为纤维肌痛患者15年来的首个新治疗选择。”
Lederman博士继续说道：“纤维肌痛是原型的痛觉异常综合症和慢性重叠性疼痛症（COPC）3,4,5. 我们在纤维肌痛中的结果表明了TNX-102 SL在治疗其他COPC（如后脑震荡综合症6）方面的潜力，其中睡眠障碍与持续和严重程度相关。此外，我们预计将在这个季度开始在美国北卡罗来纳大学进行由美国国防部（DoD）资助的优化急性应激反应干预（OASIS）试验，该试验是基于调查者发起的新药（IND）申请，用于处理车祸后立即出现的急性压力障碍/急性应激反应的TNX-102 SL试验的招募工作。”
Tonix仍然按计划准备在2024年下半年向FDA提交TNX-102 SL用于纤维肌痛管理的新药申请（NDA）。预计将于2025年做出批准决定。
Moldofsky H，等人。心身医学杂志。1975年; 37：341-51
Moldofsky H，Scarisbrick P。心身医学杂志。1976年; 38：35-44
Fitzcharles MA等。柳叶刀。2021年; 397：2098-110
Clauw DJ。《Ann Rheum Dis》。2024年首次在线发表。
Kaplan Cm等。Nat Rev Neurol。2024年; 20，347-363。
6Kureshi S等。 Healthcare (Basel) 2024年12期：289。
关于纤维肌痛
纤维肌痛是一种由中枢神经系统内的感觉和疼痛信号放大所致的慢性疼痛疾病。纤维肌痛病患在美国超过1000万，其中大部分是女性。纤维肌痛的症状包括慢性广泛性疼痛、不良恢复性睡眠、疲劳和脑雾（认知功能障碍）。其他相关症状包括情绪障碍，如焦虑和抑郁、头痛以及腹痛或痉挛。患有纤维肌痛的人们经常面临着日常活动的困难，其生活质量降低且容易发生残障。医生和患者对目前市场上的产品普遍表示不满。根据美国国家科学院的最近一份报告，纤维肌痛是一种可诊断的疾病，在长期新冠肺炎的情况下也可能出现。
关于TNX-102 SL
TNX-102 SL是一种中枢作用的非阿片类非成瘾性睡前调查药物。该片剂是环苯磺酸环丙司平的专利舌下制剂，用于管理纤维肌痛。2023年12月，该公司宣布在纤维肌痛管理的TNX-102 SL第二个关键3期临床试验RESILIENt中取得了高度统计学意义和临床意义的上市结果。在研究中，与安慰剂相比，TNX-102 SL 达到了预先确定的主要终点，显著减少了参与者的日常疼痛（p=0.00005）。在改善睡眠质量、减轻疲劳以及改善整体纤维肌痛症状和功能方面，所有六个关键的次要终点也均取得了统计学和临床意义上的显著结果。TNX-102 SL在纤维肌痛的第一个具有统计学意义的3期临床试验RELIEF于2020年12月完成。它达到了预先确定的主要终点-与安慰剂相比每日疼痛的减轻（p=0.010），并在关键的次要终点上显示了活性。在这两个关键试验中，最常见的治疗细胞出现的不良事件是在给药部位出现的舌头或口腔麻木感，这种感觉与服药时间有关，是自限制的，从未被评为严重的，并很少导致试验中止（每项研究中各有一个参与者）。TNX-102 SL最近被FDA授予快速通道资格，用于管理纤维肌痛，并计划于2024年下半年提交新药申请给FDA。
关于无器质性疼痛
痛觉过敏原性疼痛是针对实际或威胁性组织损伤没有证据的改变感觉或nociceptors激活的疼痛的第三类疼痛。它的潜在病理生理机制涉及中枢神经系统（CNS）对疼痛处理的变化。2017年，国际疼痛研究协会（IASP）正式承认痛觉过敏症候群，还包括若干其他慢性重叠性疼痛病症：慢性疲劳综合症/慢性疲劳综合症、肠易激综合症、颞下颌关节紊乱、慢性背痛和慢性头痛。痛觉过敏性疼痛的病理生理涉及中枢敏化（CS），其中CNS的神经元变得过度兴奋，放大了疼痛信号。CS可能会被周围疼痛刺激、情绪压力或其他因素触发，导致持续的疼痛，尽管没有周围nociceptive输入。
Tonix Pharmaceuticals Holding Corp.*
Tonix是一家全面集成的生物制药公司，专注于开发、许可和商业化治疗和预防人类疾病并减轻痛苦的治疗方案。Tonix最近宣布，美国国防部，国防威胁削减局（DTRA）授予其一项合同，金额高达3400万美元，为期五年，用于开发针对CD45的TNX-4200小分子广谱抗病毒药物，以预防或治疗感染，改善军事人员在生物威胁环境中的医疗准备。Tonix拥有并运营位于MD州Frederick市的最先进的传染病研究设施。公司还拥有位于MA州Dartmouth市的符合GMP法规的先进制造工厂，专门用于生产TNX-801，一种潜在的生物制剂疫苗，GMP生产车间可随时在国家紧急情况下重新启用。Tonix的开发项目组合侧重于中枢神经系统疾病。Tonix的重点是在2024年下半年提交TNX-102 SL的NDA申请，这是一个用于管理纤维肌痛的产品候选药物，已进行了两项具有统计学意义的第三期研究。FDA已授予TNX-102 SL用于管理纤维肌痛的快速通道认定。TNX-102 SL也正在开发用于治疗急性压力反应。Tonix的中枢神经系统项目组合包括TNX-1300（古柯碱酯酶），这是一种旨在治疗古柯碱中毒的生物制品，已获得突破性疗法认定，正在进行潜在的关键第二期临床试验。Tonix的免疫学研发项目组合包括生物制品，用于治疗器官移植排斥、自身免疫病和癌症，包括TNX-1500，这是一种人类化的单克隆抗体，针对CD40配体（CD40L或CD154），用于预防移植排斥和治疗自身免疫疾病。Tonix在罕见疾病和传染病领域也有在研的产品候选药物。Tonix Medicines，我们的商业子公司，销售Zembrace SymTouch（舒马曲坦注射液）3毫克和Tosymra（舒马曲坦鼻喷雾剂）10毫克，用于成年人急性偏头痛的治疗，无论有无先兆。
Tonix的产品研发候选品是新药或生物制品，尚未获得任何适应症批准。
Zembrace SymTouch和Tosymra是Tonix Medicines的注册商标，其他所有商标均为其各自所有者的财产。
资料来源：Tonix Pharmaceuticals Holding Corp。
