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年軍工-半導體健康系統研究研討會上介紹了TNX-102 SL治療纖維肌痛的數據和分析
2024年8月28日 上午7:00 EDT 下載爲PDF
口頭報告重點介紹了TNX-102 SL（舌下環苯甲酸氯倍他索）治療的第3期確認性RESILIENt研究結果，顯示在纖維肌痛的病因疼痛和所有六個關鍵次要終點中均有統計學上顯著的改善，包括睡眠質量
新藥申報計劃順利進行，預計2024年下半年完成；FDA授予快速通道認定；預計FDA將於2025年作出決定
TNX-102 SL是一種潛在的非阿片類鎮痛藥，針對纖維肌痛中的非恢復性睡眠：事後分析突顯了病因疼痛改善與睡眠質量的強相關性
痛覺過敏性疼痛起源於大腦中變化的疼痛感知，是纖維肌痛和其他慢性重疊疼痛症狀的類型
2024年8月28日，新澤西州CHATHAm市（全球新聞社）--Tonix Pharmaceuticals Holding Corp.（納斯達克上市代碼：TNXP）（Tonix或公司）是一家擁有上市產品和發展候選藥物流水線的全面集成生物製品公司，其數據在2024年軍事衛生系統研究學術會議（MHSRS）的口頭報告中展示，該會議於2024年8月26日至29日在佛羅里達州基西米舉行。公司的報告題爲「Alleviating Agony: Novel Pain Therapeutics」，可在Tonix網站的科學報告選項卡上找到
在第3期RESILIENt研究中，TNX-102 SL達到了預先指定的主要終點，與安慰劑相比顯著減少了每日疼痛（p值=0.00005），適用於纖維肌痛患者。TNX-102 SL表現出廣泛的綜合效益，所有預先指定的六個關鍵次要終點均有統計學上顯著的改善，包括與改善睡眠質量、減少疲勞、改善患者整體評價和纖維肌痛症狀和功能有關的終點。事後分析顯示，在第14周的疼痛和睡眠質量改善之間存在顯著相關性，支持通過改善睡眠質量來實現纖維肌痛的綜合改善的觀念。TNX-102 SL的耐受性良好，與之前的研究相當，並未觀察到新的安全信號。
「像NSAIDs或阿片類傳統止痛藥物常常被證實無效，甚至有害，作爲處理纖維肌痛的策略，」tonix pharmaceuticals首席執行官Seth Lederman.D.說道。「相反，TNX-102 SL在第3期RESILIENt研究中提供了廣譜症狀緩解，並被設計爲針對非恢復性睡眠和改善睡眠質量的牀前治療。通過在纖維肌痛中進行兩項積極的第3期研究，顯示了統計學顯著的結果，我們相信TNX-102 SL有潛力成爲纖維肌痛患者15年來的首個新治療選擇。」
Lederman博士繼續說道：「纖維肌痛是原型的痛覺異常綜合症和慢性重疊性疼痛症（COPC）3,4,5. 我們在纖維肌痛中的結果表明了TNX-102 SL在治療其他COPC（如後腦震盪綜合症6）方面的潛力，其中睡眠障礙與持續和嚴重程度相關。此外，我們預計將在這個季度開始在美國北卡羅來納大學進行由美國國防部（DoD）資助的優化急性應激反應干預（OASIS）試驗，該試驗是基於調查者發起的新藥（IND）申請，用於處理車禍後立即出現的急性壓力障礙/急性應激反應的TNX-102 SL試驗的招募工作。」
Tonix仍然按計劃準備在2024年下半年向FDA提交TNX-102 SL用於纖維肌痛管理的新藥申請（NDA）。預計將於2025年做出批准決定。
Moldofsky H，等人。心身醫學雜誌。1975年; 37：341-51
Moldofsky H，Scarisbrick P。心身醫學雜誌。1976年; 38：35-44
Fitzcharles MA等。柳葉刀。2021年; 397：2098-110
Clauw DJ。《Ann Rheum Dis》。2024年首次在線發表。
Kaplan Cm等。Nat Rev Neurol。2024年; 20，347-363。
6Kureshi S等。 Healthcare (Basel) 2024年12期：289。
關於纖維肌痛
纖維肌痛是一種由中樞神經系統內的感覺和疼痛信號放大所致的慢性疼痛疾病。纖維肌痛病患在美國超過1000萬，其中大部分是女性。纖維肌痛的症狀包括慢性廣泛性疼痛、不良恢復性睡眠、疲勞和腦霧（認知功能障礙）。其他相關症狀包括情緒障礙，如焦慮和抑鬱、頭痛以及腹痛或痙攣。患有纖維肌痛的人們經常面臨着日常活動的困難，其生活質量降低且容易發生殘障。醫生和患者對目前市場上的產品普遍表示不滿。根據美國國家科學院的最近一份報告，纖維肌痛是一種可診斷的疾病，在長期新冠肺炎的情況下也可能出現。
關於TNX-102 SL
TNX-102 SL是一種中樞作用的非阿片類非成癮性睡前調查藥物。該片劑是環苯磺酸環丙司平的專利舌下製劑，用於管理纖維肌痛。2023年12月，該公司宣佈在纖維肌痛管理的TNX-102 SL第二個關鍵3期臨床試驗RESILIENt中取得了高度統計學意義和臨床意義的上市結果。在研究中，與安慰劑相比，TNX-102 SL 達到了預先確定的主要終點，顯著減少了參與者的日常疼痛（p=0.00005）。在改善睡眠質量、減輕疲勞以及改善整體纖維肌痛症狀和功能方面，所有六個關鍵的次要終點也均取得了統計學和臨床意義上的顯著結果。TNX-102 SL在纖維肌痛的第一個具有統計學意義的3期臨床試驗RELIEF於2020年12月完成。它達到了預先確定的主要終點-與安慰劑相比每日疼痛的減輕（p=0.010），並在關鍵的次要終點上顯示了活性。在這兩個關鍵試驗中，最常見的治療細胞出現的不良事件是在給藥部位出現的舌頭或口腔麻木感，這種感覺與服藥時間有關，是自限制的，從未被評爲嚴重的，並很少導致試驗中止（每項研究中各有一個參與者）。TNX-102 SL最近被FDA授予快速通道資格，用於管理纖維肌痛，並計劃於2024年下半年提交新藥申請給FDA。
關於無器質性疼痛
痛覺過敏原性疼痛是針對實際或威脅性組織損傷沒有證據的改變感覺或nociceptors激活的疼痛的第三類疼痛。它的潛在病理生理機制涉及中樞神經系統（CNS）對疼痛處理的變化。2017年，國際疼痛研究協會（IASP）正式承認痛覺過敏症候群，還包括若干其他慢性重疊性疼痛病症：慢性疲勞綜合症/慢性疲勞綜合症、腸易激綜合症、顳下頜關節紊亂、慢性背痛和慢性頭痛。痛覺過敏性疼痛的病理生理涉及中樞敏化（CS），其中CNS的神經元變得過度興奮，放大了疼痛信號。CS可能會被周圍疼痛刺激、情緒壓力或其他因素觸發，導致持續的疼痛，儘管沒有周圍nociceptive輸入。
Tonix Pharmaceuticals Holding Corp.*
Tonix是一家全面集成的生物製藥公司，專注於開發、許可和商業化治療和預防人類疾病並減輕痛苦的治療方案。Tonix最近宣佈，美國國防部，國防威脅削減局（DTRA）授予其一項合同，金額高達3400萬美元，爲期五年，用於開發針對CD45的TNX-4200小分子廣譜抗病毒藥物，以預防或治療感染，改善軍事人員在生物威脅環境中的醫療準備。Tonix擁有並運營位於MD州Frederick市的最先進的傳染病研究設施。公司還擁有位於MA州Dartmouth市的符合GMP法規的先進製造工廠，專門用於生產TNX-801，一種潛在的生物製劑疫苗，GMP生產車間可隨時在國家緊急情況下重新啓用。Tonix的開發項目組合側重於中樞神經系統疾病。Tonix的重點是在2024年下半年提交TNX-102 SL的NDA申請，這是一個用於管理纖維肌痛的產品候選藥物，已進行了兩項具有統計學意義的第三期研究。FDA已授予TNX-102 SL用於管理纖維肌痛的快速通道認定。TNX-102 SL也正在開發用於治療急性壓力反應。Tonix的中樞神經系統項目組合包括TNX-1300（古柯鹼酯酶），這是一種旨在治療古柯鹼中毒的生物製品，已獲得突破性療法認定，正在進行潛在的關鍵第二期臨床試驗。Tonix的免疫學研發項目組合包括生物製品，用於治療器官移植排斥、自身免疫病和癌症，包括TNX-1500，這是一種人類化的單克隆抗體，針對CD40配體（CD40L或CD154），用於預防移植排斥和治療自身免疫疾病。Tonix在罕見疾病和傳染病領域也有在研的產品候選藥物。Tonix Medicines，我們的商業子公司，銷售Zembrace SymTouch（舒馬曲坦注射液）3毫克和Tosymra（舒馬曲坦鼻噴霧劑）10毫克，用於成年人急性偏頭痛的治療，無論有無先兆。
Tonix的產品研發候選品是新藥或生物製品，尚未獲得任何適應症批准。
Zembrace SymTouch和Tosymra是Tonix Medicines的註冊商標，其他所有商標均爲其各自所有者的財產。
資料來源：Tonix Pharmaceuticals Holding Corp。
