Randomized, double-blind, and placebo-controlled clinical study of Milnacipran hydrochloride tablets combined with transcranial magnetic stimulation in the treatment of somatic cough disorders

Start Date01 May 2024

Sponsor / Collaborator

Shanghai Tongji Hospital

CTR20223361 / CompletedNot Applicable

盐酸米那普仑片在健康受试者中的随机、开放、单次给药、两制剂、两周期人体生物等效性研究

[Translation] A randomized, open-label, single-dose, two-formulation, two-cycle human bioequivalence study of milnacipran hydrochloride tablets in healthy subjects

采用单中心、随机、开放、两周期、自身交叉、单剂量空腹及餐后给药试验设计评价上海现代制药股份有限公司生产的盐酸米那普仑片（规格：50mg）与日本旭化成株式会社生产的盐酸米那普仑片（商品名：Toledomin®，参比制剂，50mg）在健康人群空腹、餐后口服的生物等效性，为上海现代制药股份有限公司生产的盐酸米那普仑片与日本旭化成株式会社生产的盐酸米那普仑片临床疗效的一致性提供证据。

[Translation]

A single-center, randomized, open, two-period, self-crossover, single-dose fasting and postprandial administration trial design was used to evaluate the bioequivalence of milnacipran hydrochloride tablets (specification: 50 mg) produced by Shanghai Modern Pharmaceutical Co., Ltd. and milnacipran hydrochloride tablets (trade name: Toledomin®, reference preparation, 50 mg) produced by Asahi Kasei Corporation of Japan in healthy people when taken orally on an empty stomach or after a meal, to provide evidence for the consistency of clinical efficacy of milnacipran hydrochloride tablets produced by Shanghai Modern Pharmaceutical Co., Ltd. and milnacipran hydrochloride tablets produced by Asahi Kasei Corporation of Japan.

Start Date01 Feb 2023

Sponsor / Collaborator

Shanghai Shyndec Pharmaceutical Co., Ltd.

NCT05384210 / Unknown statusNot ApplicableIIT

Effect of Milnacipran Versus Gabapentin or Combination of Both in Fibromyalgia Syndrome

Gabapentin and milnacipran (MLN) show strong evidence of reduced pain, increased sleep, and improvement in the quality of life in fibromyalgia (FM) patients.
Most FM trials focus primarily on pain reduction with monotherapy. Polypharmacy is commonly used, but supportive evidence is limited.
The gabapentin-MLN combined therapy may be more effective in female patients with FM than their monotherapy.

Start Date01 Jun 2022

Sponsor / Collaborator

Mansoura University

100 Clinical Results associated with Milnacipran Hydrochloride

100 Translational Medicine associated with Milnacipran Hydrochloride

100 Patents (Medical) associated with Milnacipran Hydrochloride

686

Literatures (Medical) associated with Milnacipran Hydrochloride

01 Sep 2024·Current rheumatology reviews

Diet and Lifestyle Modifications for Fibromyalgia

Review

Author: Ballester, Andrew M ; Joseph, Marina ; Metyas, Samy ; Metyas, Caroline ; Aung, Tun Tun ; Cheung, Jennifer

Abstract::

Fibromyalgia (FM) is a complex, widespread pain disorder characterized by symptoms such as fatigue, sleep deprivation, mental fog, mood swings, and headaches. Currently, there are only three FDA-approved medications for FM patients: duloxetine, milnacipran, and pregabalin, with outcomes frequently being inadequate. This research team aims to investigate the effects of diet and lifestyle modifications on FM, with emphasis on anti-inflammatory diet, antioxidants, and gluten-free diets, as well as supplementation with Magnesium, CQ10, and Vitamin D, microbiome, sleep, exercise, and cognitive behavioral therapy. We reviewed the pathophysiology of certain foods that can be proinflammatory with the release of cytokines leading to activation of pain, fatigue and aggravation of the majority of Fibromyalgia symptoms. A literature review was performed by identifying FM articles published between 1994 and 2022 via PubMed and EMBASE databases, with particular emphasis on randomized controlled trials, meta-analysis, and evidence-based treatment guidelines. This review article was completed by a comprehensive narrative review process, in which our team systematically examined relevant scientific literature to provide a comprehensive overview of the significant role that diet and other lifestyle modifications play in mediating symptoms of Fibromyalgia. We propose that diet modifications and lifestyle changes, such as sleep, exercise, and weight loss, can be important steps in managing FM.

01 Nov 2023·Biological & pharmaceutical bulletin

Differential Contribution of 5-HT4, 5-HT5, and 5-HT6 Receptors to Acute Pruriceptive Processing Induced by Chloroquine and Histamine in Mice

Article

Author: Nishimori, Toshikazu ; Kanemaru-Kawazoe, Anna ; Haruta-Tsukamoto, Ayaka ; Funahashi, Hideki ; Ishida, Yasushi ; Miyahara, Yu ; Kogoh, Yoichiro ; Hirano, Yoji

The involvement of serotonin (5-HT) and/or noradrenaline in acute pruriceptive processing in the central nervous system (CNS) has been reported using antidepressants, such as milnacipran, a serotonin and noradrenaline reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant; however, the roles of 5-HT receptor family in acute pruriceptive processing have not been fully elucidated in the CNS. In the present study, scratching behavior induced by chloroquine (CQ) was ameliorated by milnacipran or mirtazapine, and these effects were reversed by SB207266, a 5-HT₄ antagonist, or SB258585, a 5-HT₆ antagonist, but not by SB258585, a 5-HT₅ antagonist. Moreover, CQ-induced scratches were mitigated by intrathecal injection of 5-HT₄ agonists, such as BIMU8 and ML10302, and the 5-HT₆ agonist, WAY208466. Conversely, histamine-induced scratches were not affected by the 5-HT₄ agonists or a 5-HT₆ agonist. Similarly, the amelioration of histamine-induced scratches by these antidepressants was not reversed by the 5-HT₄, 5-HT₅, or 5-HT₆ receptor antagonist. Therefore, 5-HT is involved in the amelioration of CQ-induced scratches by milnacipran and mirtazapine, and 5-HT₄, 5-HT₅, and 5-HT₆ receptors play differential roles in acute pruriceptive processing after administration of CQ or histamine.

31 Oct 2023·Cureus

Beyond the Pain: A Systematic Narrative Review of the Latest Advancements in Fibromyalgia Treatment

Review

Author: Nallakumarasamy, Arulkumar ; Khanna, Manish ; Jeyaraman, Naveen ; Gupta, Ashim ; Jeyaraman, Madhan ; Yadav, Sankalp ; Ram, Pothuri R

Fibromyalgia is a complex chronic pain disorder that significantly impacts the quality of life of affected individuals. The etiology of fibromyalgia remains elusive, necessitating effective treatment options. This review aims to provide an overview of current treatment options for fibromyalgia and highlight recent updates in managing the condition. The methodology employed in this systematic review comprised the following key steps. We conducted a comprehensive search across various databases to identify pertinent studies published between 2000 and 2023. Inclusion criteria were defined to specifically target studies involving adult individuals diagnosed with fibromyalgia, with a focus on both pharmacological and non-pharmacological interventions for managing the condition. The review encompassed a range of study types, including randomized controlled trials, observational studies, and systematic reviews. To ensure the quality of the selected studies, we employed appropriate assessment tools, and data extraction and synthesis adhered to established guidelines. This rigorous approach allowed for a robust analysis of the literature on fibromyalgia management. In the course of our review, it became evident that a spectrum of treatment approaches holds significant promise in the management of fibromyalgia. Specifically, pharmacological interventions, including selective serotonin-norepinephrine reuptake inhibitors, anticonvulsants, cannabinoids, tropisetron, and sodium oxybate, have exhibited substantial potential in alleviating fibromyalgia symptoms. Concurrently, non-pharmacological strategies, such as cognitive-behavioral therapy, exercise regimens, and complementary and alternative therapies, have yielded positive outcomes in improving the condition's management. Recent developments in the field have introduced innovative pharmacological agents like milnacipran and pregabalin, in addition to non-pharmacological interventions like mindfulness-based stress reduction and aquatic exercise, expanding the array of options available to enhance fibromyalgia care and alleviating patient symptoms. Fibromyalgia necessitates a multidisciplinary approach to treatment, encompassing both pharmacological and non-pharmacological interventions. Recent updates in fibromyalgia management offer additional options to alleviate symptoms and improve the quality of life for individuals with fibromyalgia. Healthcare professionals should remain informed about these advancements to provide evidence-based care, addressing the complex symptoms associated with fibromyalgia and enhancing patient outcomes.

News (Medical) associated with Milnacipran Hydrochloride

21 May 2024

·www.biospace.com

Tonix Pharmaceuticals Announces Key Findings from Initial Phase of EVERSANA Market Opportunity Analysis for Tonmya™ for the Management of Fibromyalgia

Tonmya is a potential new first-line, centrally acting non-opioid analgesic for the management of fibromyalgia, supported by statistically significant results from two Phase 3 trials Primary physician research found high level of interest in Tonmya as a potential new treatment option for fibromyalgia Significant dissatisfaction reported with drugs currently approved by FDA for the treatment of fibromyalgia Analysis of claims data revealed that addictive opioids are prescribed more frequently than currently approved drugs following fibromyalgia diagnosis New Drug Application (NDA) submission to the FDA on track for the second half of 2024 CHATHAM, N.J., May 21, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals, Inc. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, announced today that EVERSANA® Life Science Services, LLC, a leading provider of commercialization services to the global life sciences industry, completed the initial phase of an assessment of the U.S market opportunity for TonmyaTM (also known as TNX-102 SL, cyclobenzaprine HCl sublingual tablets), a potential new first line therapy for the management of fibromyalgia. Tonix previously announced that EVERSANA was selected to support the launch strategy and commercial planning of Tonmya. Specifically, EVERSANA is working with Tonix to assess the fibromyalgia landscape and help plan an efficient go-to-market (GTM) strategy. “The primary research and analysis conducted by EVERSANA provides valuable insights and informs the vision for the commercialization of Tonmya,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “We are excited to refine our business strategy for the anticipated launch of Tonmya in 2025. It has been approximately fifteen years since patients suffering with fibromyalgia have been provided a new therapeutic option. The market research conducted by EVERSANA with physicians indicates a continued high unmet need, with the need ranked > 4.0 on a 5-point scale.” Dr. Lederman continued, “We were surprised to learn that opioids dominate the fibromyalgia prescription market, despite the well-known risks of dependency. Opioids are prescribed to more patients following fibromyalgia diagnosis than all the FDA-approved fibromyalgia drugs combined. If approved, we believe that Tonmya can provide a non-opioid, centrally-acting solution for fibromyalgia patients. This is corroborated by EVERSANA’s primary market research in which physicians indicated median interest of 4.0 on a 5-point scale and intended use of Tomya in 40% of their fibromyalgia patients, upon approval.1 We look forward to submitting the NDA for Tonmya in the second half of this year and expect an FDA decision on approval in 2025.” EVERSANA’s analysis of the market size was based on medical claims databases and epidemiological studies on prevalence and diagnosis2. Primary research with physicians was conducted to test the potential adoption of Tonmya based on its activity and tolerability. Key findings from claims data analyses2: ~2.7 million adults in the U.S. currently diagnosed and treated for fibromyalgia. ~90 percent of patients diagnosed with fibromyalgia are female. Percentage of fibromyalgia patients who were prescribed certain drugs3: FDA-approved fibromyalgia drug prescriptions: Duloxetine (generic Cymbalta®): 23%, pregabalin (generic Lyrica®): 13%, and Savella® (milnacipran): 1% Off-label drug prescriptions: Gabapentin: 26%, hydroxycodone: 20%, cyclobenzaprine: 18%, oxycodone: 19%, tramadol: 13%, meloxicam: 12%, and amitriptyline: 6% Off-label opioids prescriptions: Hydroxycodone: 20%, oxycodone: 19%, and tramadol: 13% Targeted prescriber strategy for launch. High prescribers are rheumatologists, pain medicine specialists, primary care physicians, neurologists, and psychiatrists. ~50 percent of diagnosed fibromyalgia patients are covered by Medicare. Medicare population stands to benefit from a decrease in out-of-pocket prescription drug liability to $2,000 per year when the changes from the Inflation Reduction Act are enacted in 2025. Key findings from primary physician research4: High level of dissatisfaction with currently prescribed drugs. Physicians interviewed estimate that 85% of their patients fail first-line therapy due to efficacy and tolerability issues and 79% of their patients are on multiple therapies. Prescribers indicate high unmet need in fibromyalgia, ranked >4.0 on a 5-point scale. High level of interest in Tonmya from physicians interviewed as a potential new treatment option based on favorable activity and tolerability pro in Tonmya fibromyalgia clinical studies. Median interest in Tonmya of 4 on a 5-point scale. Physicians indicated intended use of Tonmya in 40% of their fibromyalgia patients.1 Tonmya is a centrally acting, non-opioid medication. As previously announced, Tonix’s second statistically significant Phase 3 study, RESILIENT, 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 (p=0.001 or better) were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue, and improving overall fibromyalgia symptoms and function. Tonix plans to submit an NDA to the U.S. Food and Drug Administration (FDA) in the second half of 2024 for Tonmya for the management of fibromyalgia and has scheduled a Type B pre-NDA meeting with FDA for the second quarter of 2024. 1 40% was the median preference share amongphysicians interviewed,assuming no market access barriers. 2EVERSANA analysis of claims database, May 2024; commissioned by Tonix 3Note: the total number of patients is greater than 100% because of switching between medications and polypharmacy. 4EVERSANA primary physician research, May 2024; commissioned by Tonix About Tonmya* (also known as TNX-102 SL) Tonmya is a centrally acting, non-opioid, non-addictive, bedtime medication. 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, a second positive Phase 3 clinical trial of Tonmya for the management of fibromyalgia. In the study, Tonmya 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 key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first positive Phase 3 trial of Tonmya 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. *Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration (FDA) as the tradename for TNX-102 SL for the management of fibromyalgia. Tonmya has not been approved for any indication. About EVERSANA® EVERSANA® is a leading independent provider of global services to the life sciences industry. The company’s integrated solutions are rooted in the patient experience and span all stages of the product life cycle to deliver long-term, sustainable value for patients, prescribers, channel partners and payers. The company serves more than 650 organizations, including innovative start-ups and established pharmaceutical companies, to advance life sciences solutions for a healthier world. To learn more about EVERSANA, visit eversana.com or connect through LinkedIn and X. 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’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya, a product candidate for which two positive Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase) a biologic designed to treat cocaine intoxication with Breakthrough Therapy designation. 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. This press release and further information about Tonix can be found at . Forward-Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully commercialize any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission (the “SEC”) on April 1, 2024, and periodic reports filed with the SEC on or after the date thereof. All of Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. Investor Contact Jessica Morris Tonix Pharmaceuticals investor.relations@tonixpharma.com (862) 904-8182 Peter Vozzo ICR Westwicke peter.vozzo@westwicke.com (443) 213-0505 Media Contact Katie Dodge LaVoieHealthScience kdodge@lavoiehealthscience.com (978) 360-3151 Matt Braun EVERSANA Matt.braun@eversana.com

Phase 3NDAClinical ResultBreakthrough Therapy

26 Feb 2024

·www.biospace.com

New Drug Study Shows Improving Sleep Quality Can Relieve Fibromyalgia Pain

Bedtime drug being developed by Tonix relieved pain by targeting fibromyalgia's characteristic "non-restorative sleep": Potential for FDA Approval in 2025 CHATHAM, NJ / ACCESSWIRE / February 26, 2024 / People who are suffering from fibromyalgia pain are closer to a new option for treatment that targets their characteristically poor sleep quality. Tonix Pharmaceuticals (TNXP) reported positive study results for its sleep-quality targeted therapy in late December. The drug reduced widespread pain in fibromyalgia reported by study volunteers, a sign it could be the first in a new class of painkiller to be approved for use in fibromyalgia. In the latest fibromyalgia phase 3 study, Tonix's product candidate Tonmya®* improved fibromyalgia pain with a highly statistically significant p-value of 0.00005 on the primary endpoint which was the improvement in daily pain relative to placebo. The results also showed favorable tolerability with no unexpected side effects. About 10 million Americans suffer from fibromyalgia and the majority are prescribed a medicine for the characteristic widespread pain. It is known that the brain creates the feeling of pain. Fibromyalgia results when the brain becomes overly sensitive. The fibromyalgia brain sounds the pain alarm in response to sensory experiences that most healthy people ignore. Brain imaging studies have revealed that the fibromyalgia pathology activates the same parts of the brain that pain normally activates in healthy people. Consequently, the pain that fibromyalgia patients experience is real to them. It is unknown how fibromyalgia turns up the volume on brain sensitivity. It is also unknown how good sleep is able to reset the fibromyalgia brain's over-sensitive perception. The experimental medicine targets the characteristic sleep disturbance of fibromyalgia, called "non-restorative sleep." People with fibromyalgia wake up feeling unrefreshed because their sleep fails to provide the restorative properties that healthy people enjoy. While targeting sleep is the novel mechanism of the new drug, it also provides a direct benefit because sleep disturbance is one of the core symptoms of fibromyalgia. In the study, Tonmya improved sleep quality relative to placebo by both the PROMIS sleep disturbance scale p = 0.0000001 and a daily sleep diary p = 0.0007. The role of poor sleep in causing, perpetuating or exacerbating fibromyalgia has been recognized for more than 50 years. In the 1970's, Professor Harvey Moldofsky at the University of Toronto deprived undergraduates of deep sleep and found that most of them developed symptoms of fibromyalgia. Developing drugs to target fibromyalgia's characteristic sleep problem has been challenging. Daily bedtime Ambien® (zolpidem) was studied and did not improve fibromyalgia. Intriguing results were achieved by treating fibromyalgia patients with the sleep drug Xyrem® (sodium oxybate). That drug induces a profoundly deep sleep and is approved for narcolepsy. It is hard to rouse people after taking Xyrem. While the results with Xyrem were scientifically interesting, an advisory committee to the U.S. Food and Drug Administration (FDA) voted against approval for fibromyalgia and the sponsor, Jazz Pharmaceuticals decided not to pursue approval. Because of the risk of diversion for date rape, Xyrem is burdened by a complex risk evaluation and mitigation strategy (REMS) program. This history with Ambien shows that the type of sleep drug and its particular effect on sleep are important in determining whether it will be therapeutic for fibromyalgia. Tonix's new drug candidate Tonmya™ improves sleep quality by blocking four receptors in the brain, each of which plays roles in disturbing sleep. The normal function of these four receptors is to increase alertness, vigilance or wakefulness or to sound the alarm to wake up. Consequently, when they fire during sleep, they can play pathological roles in fibromyalgia. During the time fibromyalgia patients want to sleep, these receptors can disrupt sleep quality. By blocking these receptors during sleep, Tonmya improves the quality of sleep and removes an obstacle to recovery. Tonix's drug, also known as TNX-102 SL, belongs to a new class of medicines for fibromyalgia. Tonmya's active ingredient has a chemical structure with three rings, so it is called a "tricyclic." The Tonix drug is a sublingual tablet to be taken at bedtime, designed to deliver the active ingredient into the brain during sleep and reduce its presence during wakefulness. This is the first program pursuing a drug to improve sleep quality in fibromyalgia since 2009 that is headed to the FDA for a decision on approval. Tonix says it intends to approval by submitting a New Drug Application (NDA) with the FDA in the second half of this year. The company expects a decision from the FDA in 2025. "If and when Tonmya is approved, it will offer a new first line treatment option for fibromyalgia patients," Tonix Chief Executive Officer Seth Lederman, M.D., said. "Ultimately, we believe Tonmya will also be an option for patients who need pain relief but can't tolerate or don't respond to the currently marketed drugs for fibromyalgia. Because Tonmya targets sleep quality, we believe it's a major step forward in both the treatment of fibromyalgia and in understanding the roles of non-restorative sleep in causing or exacerbating fibromyalgia." With the current FDA-approved drugs, fibromyalgia patients face tough choices: take Cymbala® (duloxetine) from Eli Lilly or Savella® (milnacipran) from Abbvie, Inc. and risk insomnia or take Lyrica® (pregabalin) from Pfizer, Inc. and risk increased fatigue. Tonmya demonstrated improved pain, sleep and fatigue in fibromyalgia patients in its confirmatory phase 3 study. New Jersey-based Tonix studied Tonmya in three late-stage, or phase 3, trials that enrolled more than 1,400 subjects with fibromyalgia. Tonix also studied TNX-102 SL in three phase 3, trials that enrolled more than 1,200 subjects with posttraumatic stress disorder (PTSD) which has a different sleep disturbance. Axsome plans to new drug application this quarter for esreboxetine for the management of fibromyalgia. Esreboxetine has a mechanism similar to Cymbalta and Savella but is more specific for norepinephrine reuptake. *Tomya is conditionally accepted by the U.S. Food and Drug Administration (FDA0 as the tradename for TN-102 SL for the management of fibromyalgia. Tonmya is an investigational new medicine and has not been accepted for any indication. Featured photo by Jonathan Borba on Unsplash. Click here for more information on Tonix Pharmaceuticals: Important notice, please read: Certain statements in this document are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as "anticipate," "believe," "forecast," "estimate," "expect," and "intend," among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval, and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the "SEC") in March 2023, and periodic reports filed with the SEC on or after the date thereof. All Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. This is not a solicitation of any offer to buy or sell. Redington, Inc. is paid by Tonix Pharmaceuticals Holding Corp. for investor relations services, and its employees or members of their families may from time to time own an equity interest in companies mentioned herein. Contact Tonix Pharmaceuticals Holding Corp. Jessica Morris (corporate) investor.relations@tonixpharma.com SOURCE: Tonix Pharmaceuticals View the original press release on accesswire.com

Clinical ResultPhase 3Drug ApprovalNDA

01 Feb 2024

·www.biospace.com

New Hope For Fibromyalgia Patients: Tonix Details Results Of Second Successful Phase 3 Trial And Plans To File For FDA Approval

Fibromyalgia candidate TNX-102 SL hits primary endpoint of daily pain reduction (p=0.00005) Combination of broad-spectrum relief and favorable tolerability seen as distinguishing, competitive features Company plans to NDA for FDA approval in 2H 2024 CHATHAM, NJ / ACCESSWIRE / February 1, 2024 / Tonix Pharmaceuticals, Inc. (NASDAQ:TNXP) appears to have a potential new weapon against fibromyalgia for the 6-12 million adults in America suffering from its debilitating effects. It has to do with sleep quality, not sleep quantity. Tonix's candidate drug TNX-102 SL*, which just completed its second successful Phase 3 clinical trial, targets poor sleep quality - not sleep quantity - as the key mechanism to improve the daily lives of people afflicted with fibromyalgia. Traditional sleeping pills, which are called sedatives or hypnotics, speed the onset of sleep, and increase the amount of time spent asleep. But these barbiturate, "benzo" or "non-benzo" type drugs often impair the quality of sleep. The quality of sleep is usually measured by how someone feels the next day. Fibromyalgia patients suffer from poor sleep quality. A core pathology of the fibromyalgia syndrome prevents affected patients from being able to get restorative sleep. Tonix believes TNX-102 SL's ability to facilitate restorative sleep is what drove the successful efficacy and tolerability outcomes in two successful Phase 3 trials in the management of fibromyalgia. TNX-102 SL treatment is based on the hypothesis that poor sleep is an obstacle to recovery and that if the obstacle of poor sleep quality can be addressed, then fibromyalgia patients have a better chance at recovery. A filing for marketing approval with the FDA is scheduled for the second half of this year, the company said. "'I hurt all over and I can't sleep,' are the two most frequent complaints of fibromyalgia patients", says Seth Lederman, MD, the CEO of Tonix, who years ago cared for fibromyalgia patients at the rheumatology clinic at Columbia Medical School. He added, "Sometimes fibromyalgia patients will volunteer that a good night's sleep can bring relief." The company's latest Phase 3 trial in fibromyalgia (457 patients randomized 1:1 drug to placebo) showed TNX-102 SL successfully improved sleep quality over placebo with a highly significant p-value of 0.0000001 in the PROMIS sleep scale and achieved its primary endpoint of daily pain reduction with a highly statistically significant p-value of 0.00005. Improved Sexual Function in Women "We believe the overall success of the trial and the strength of the effect on the primary endpoint are due to the kind of sleep fibromyalgia patients experience when they are taking TNX-102 SL therapy," says Dr. Lederman. "Our studies have shown TNX-102 SL increases sleep quality in fibromyalgia. Beyond sleep and pain, TNX-102 SL also improves other key characteristics of the fibromyalgia syndrome. For example, TNX-102 SL treated patients had less fatigue, fewer symptoms and better function. So far, TNX-102 SL has not shown any effects on weight or blood pressure in our trials. In addition, in the latest study, TNX-102 SL therapy improved sexual function in women as measured by the CSQ-14 score." TNX-102 SL's ability to reduce pain, coupled with its tolerability and favorable side effects profile, may give hope to fibromyalgia patients. If approved by the FDA, TNX-102 SL would be the first new drug approved for fibromyalgia in more than a dozen years. It would also be the first member of a new class of drugs for fibromyalgia, since it has a totally new mechanism of action, relative to the three drugs that have been approved. Three drugs have been FDA-approved for fibromyalgia, but their long-term use is often problematic due to side effects. Widespread dissatisfaction with the current medicines is reported. The three currently FDA-approved medicines for fibromyalgia are Cymbalta®, Lyric®, and Savella®. They are generally thought to be effective in reducing pain. None is associated with improvements in both sleep and fatigue, like TNX-102 SL. Some of the treatment-limiting side effects of these medicines include weight gain, blood pressure, and sexual dysfunction. Despite these shortcomings, Cymbalta and Lyrica, both now off patent, enjoyed combined annual peak sales of approximately $10 billion. The unmet treatment needs in fibromyalgia lead many patients to switch frequently between approved drugs, and then to off-label drugs, home remedies, and addictive opioids. "Fibromyalgia is a chronic condition that often persists for decades. It can be treated, but there is no cure yet", Dr. Lederman adds. "Adherence to the prescribed medicines is critical to achieving the best outcomes. Therefore, tolerability is important. We think TNX-102 SL has the potential to be a first-line medicine suitable for long-term use in managing fibromyalgia." The recently reported RESILIENT Phase 3 trial and the earlier Phase 3 RELIEF trial completed in 2020 position the company to submit a New Drug Application (NDA) to the FDA under the 505(b)(2) regulatory approval pathway, which it plans to do in the second half of 2024. The company said it is on track to supply the U.S. market upon FDA approval. Tonix has several other category-leading drug candidates in development. Among them are TNX-2900 for Prader-Willi syndrome, TNX-1500 for organ transplant rejection and autoimmune diseases, and TNX-1300, an antidote to cocaine intoxication. CLICK HERE for more information on Tonix Pharmaceuticals *Tonix's product development candidates, including TNX-102 SL, are investigational new drugs or biologics and have not been approved for any indication. Featured photo by National Cancer Institute on Unsplash. Disclosures: Important notice, please read: Certain statements in this document are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as "anticipate," "believe," "forecast," "estimate," "expect," and "intend," among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval, and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the "SEC") in March 2023, and periodic reports filed with the SEC on or after the date thereof. All Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. This is not a solicitation of any offer to buy or sell. Redington, Inc. is paid by Tonix Pharmaceuticals Holding Corp. for investor relations services, and its employees or members of their families may from time to time own an equity interest in companies mentioned herein. Contact: Tonix Pharmaceuticals Holding Corp. Jessica Morris investor.relations@tonixpharma.com SOURCE: Tonix Pharmaceuticals View the original press release on accesswire.com

Phase 3Clinical ResultNDA

100 Deals associated with Milnacipran Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D01107	Milnacipran Hydrochloride	N06AX17	DB04896

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Fibromyalgia	US	AbbVie, Inc.	14 Jan 2009
Depressive Disorder	JP	Pierre Fabre SA	22 Sep 1999
Depressive Disorder	JP	Asahi Kasei Corp.	22 Sep 1999

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01393522 (CTgov)	Not Applicable	Pain \| Migraine Disorders	37	Milnacipran (Milnacipran)	tbuejuiraq(wdyderycqi) = ocgbybrapg lovkdhweph (jvxspvnztg, ldilnmjcne - kyitkqwcpv) View more	-	12 Aug 2022
				Placebo (Placebo)	tbuejuiraq(wdyderycqi) = ignulrsdow lovkdhweph (jvxspvnztg, amguvryjtq - ecsuxfaafd) View more
NCT01288937 (CTgov)	Phase 3	Pain \| Peripheral Nervous System Diseases	6	Milnacipran (Milnacipran)	useeosjssl(takhmxesqf) = eeyezejzdg yrxbddtrbm (tgnweydjsz, hfjmnwarfq - vvdfyacjpt) View more	-	03 Sep 2020
				Placebo (Placebo)	useeosjssl(takhmxesqf) = xhmkmbviso yrxbddtrbm (tgnweydjsz, hjsodmymcz - uxpcmwimim) View more
NCT01337700 (CTgov)	Phase 4	Autistic Disorder \| Autism Spectrum Disorder \| Asperger Syndrome	10	Milnacipran (Milnacipran)	pykxcwxzhv(gzeezdzfqo) = qychyseqzj ssbabaimbj (gpxekqvieq, adjzoktwiu - cpmrnypqes) View more	-	27 Feb 2020
				Placebo (Placebo)	pykxcwxzhv(gzeezdzfqo) = rtqgdwtuvu ssbabaimbj (gpxekqvieq, ytanlizrmn - hvurxvlmvy) View more
NCT01288807 (CTgov)	Phase 4	Pain \| Fibromyalgia	8	Milnacipram	npxybuehms(jwtivwvtut) = yjxykexyaf waczswfils (zuahogqjvl, zjkgndstfq - qawfkoxxzn) View more	-	24 Sep 2019
NCT01328002 (CTgov)	Phase 2	Fibromyalgia	116	Placebo (Placebo)	ecufxwhsws(zxzzlcssex) = lwwbzxogik dwczkytmpl (daembttnaw, lwqdnfhudf - enakdvzimk) View more	-	14 May 2019
				Milnacipran (Milnacipran)	ecufxwhsws(zxzzlcssex) = wtuoprjkst dwczkytmpl (daembttnaw, kwnouilwnm - wiucodclhz) View more
NCT01294059 (Pubmed \| J Pain) Manual	Phase 1	Pain \| Fibromyalgia \| Hyperalgesia	46	milnacipran	vptxwoovul(kbhimwwfta) = significantly declined by 15%, but this improvement was not statistically different between milnacipran and placebo kwrvlrgshd (msbxsmhuov )	Negative	01 Aug 2015
				Placebo
NCT01234675 (CTgov)	Phase 4	Dyssomnias \| Fibromyalgia \| Sleep	19	Milnacipran (Milnacipran)	bvphiqsmam(ioppadpbwm) = safhckkjrf tjdgibcdfx (xjnzyvvfcu, zwajvpolfe - gfblxlzotk) View more	-	22 Jul 2015
				Placebo (Placebo)	bvphiqsmam(ioppadpbwm) = iyhxqejsxr tjdgibcdfx (xjnzyvvfcu, hrblunxfxi - sjnbyhvttm) View more
NCT01173055 (CTgov)	Phase 4	Pain \| Fibromyalgia	22	milnacipran (Milnacipran)	vhrdbjurrf(bxzriqqnbh) = mttlohthqx cgvoizjkqo (fodqmfalqr, enqaqfcgzr - fgzlvffweb) View more	-	20 Feb 2015
				Placebo (Placebo)	vhrdbjurrf(bxzriqqnbh) = qipjzfaupr cgvoizjkqo (fodqmfalqr, qhadqscebv - tpscywykwh) View more
NCT01510457 (CTgov)	Phase 4	Chronic Pain \| Osteoarthritis, Knee	46	Milnacipran (Milnacipran)	qtzlrujczh(bgslovfsnw) = lmwbdhjnqs bibfhlfsah (imtxocxldc, qsnmuizaka - xvcsidpqny) View more	-	22 Jan 2015
				Placebo (Sugar Pill)	qtzlrujczh(bgslovfsnw) = oewplbtghw bibfhlfsah (imtxocxldc, pssmsjpwdh - zknnswazsr) View more
NCT01207453 (CTgov)	Phase 4	Arthralgia \| Rheumatoid Arthritis	49	placebo (Placebo)	yjvwqeyjqh(mvcclouudy) = msucymyvtf znddxecrss (ltuwraxyho, nzpqkygfpm - ejpveovwkp) View more	-	17 Nov 2014
				Milnacipran (Milnacipran)	yjvwqeyjqh(mvcclouudy) = xteucowfxp znddxecrss (ltuwraxyho, eqkkrdakmy - hcwnmjzwsg) View more

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