Oxytocin

CHATHAM, N.J., Dec. 17, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), today announced that the U.S. Food and Drug Administration (FDA) has accepted the filing of its New Drug Application (NDA) for TNX-102 SL (cyclobenzaprine HCl sublingual tablets), a 5.6 mg, non-opioid, centrally-acting analgesic, for the management of fibromyalgia. The FDA is expected to assign the NDA a Prescription Drug User Fee Act (PDUFA) target action date in a Day 74 Letter. At that time, the FDA will also communicate to Tonix whether Priority Review has been granted. TNX-102 SL was granted Fast Track designation for fibromyalgia by the FDA in July of 2024. Fast Track is designed to expedite FDA review of important new drugs to treat serious conditions and fill an unmet medical need. “The FDA’s acceptance of our NDA represents another step forward as we pursue our goal of delivering the first member of a new class of medicines for the management of fibromyalgia, a condition affecting over 10 million adults in the U.S.,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “The fibromyalgia community, comprised of patients and their families and support groups, has been waiting for a new drug for over 15 years. Analysis of insurance claims in the U.S., commissioned by Tonix, have shown that 18 months after diagnosis, fibromyalgia patients were more likely to be prescribed addictive opioids than all three of the FDA-approved drugs combined.” Dr. Lederman continued, “We look forward to working closely with the FDA throughout the NDA review period with the goal of bringing TNX-102 SL to the market to address the significant unmet needs of the fibromyalgia community as quickly as possible. Furthermore, this is an important milestone as we advance our commercial preparations in anticipation of a potential approval in 2025 with an accomplished commercial leadership team already in place, supporting our marketed products 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.” The NDA is supported by data from two 14-week double-blind, randomized, placebo-controlled Phase 3 clinical trials evaluating the safety and efficacy of TNX-102 SL as a bedtime treatment for fibromyalgia. The first Phase 3 trial, RELIEF, of TNX-102 SL 5.6 mg in fibromyalgia, completed in December 2020, met its pre-specified primary endpoint of significantly reducing daily pain compared to placebo (p=0.010). In the confirmatory Phase 3 RESILIENT study in fibromyalgia, completed in December 2023, TNX-102 SL again met the pre-specified primary endpoint of significantly reducing daily pain compared to placebo (p =0.00005). In both trials, TNX-102 SL was generally well tolerated with an adverse event profile comparable to prior studies and with no new safety signals observed. 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). Excluding COVID-19, systemic adverse events in each of the two studies was lower than 4.0%. Tonix believes the submitted dossier contains the requisite safety and efficacy data from two adequate and well-controlled studies to support NDA approval. About Fibromyalgia Fibromyalgia is a common chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system, called central sensitization. Brain imaging studies have localized the functional disorder to the brain’s insula and anterior cingulate cortex. 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 depression, anxiety, headaches and abdominal pain or cramps. Individuals suffering from fibromyalgia often struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products. Fibromyalgia is now recognized as the prototypic nociplastic syndrome. Nociplastic pain is the third primary type of pain in addition to nociceptive pain and neuropathic pain. Many patients present with pain syndromes that are a spectrum of mixtures of the three primary types of pain. Nociplastic syndromes are associated with central and peripheral sensitization. Fibromyalgia can occur without any identifiable precipitating event. However, many fibromyalgia cases follow one or more precipitating event(s) including: post-operative pain, acute or chronic nociceptive or neuropathic pain states; recovery from an infectious illness; a cancer diagnosis or cancer treatment; a metabolic or endocrine stress; or a traumatic event. In the cases of recovery from an infectious illness, fibromyalgia is considered an Infection-Associated Chronic Condition. In addition to fibromyalgia cases associated with other conditions or stressors, the U.S. National Academies of Sciences, Engineering, and Medicine, has concluded that fibromyalgia is a diagnosable condition that can occur after recovery from COVID-19 in the context of Long COVID. Fibromyalgia is also recognized as a Chronic Overlapping Pain Condition, which is a group of related conditions including, chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), irritable bowel syndrome, endometriosis, low back pain, post-concussive syndrome (also known as mild traumatic brain injury), chronic Lyme Disease, chronic diabetic neuropathy and chronic post-herpetic neuralgia. About TNX-102 SL TNX-102 SL is a centrally acting, non-opioid investigational drug, designed for chronic use. The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed for bedtime dosing for the management of fibromyalgia. Cyclobenzaprine potently binds and acts as an antagonist at four different post-synaptic neuroreceptor subtypes: serotonergic-5-HT 2A , adrenergic-α 1 , histaminergic-H 1 , and muscarinic-M 1 -cholinergic receptors. Together, these interactions are believed to target the non-restorative sleep characteristic of fibromyalgia that was identified by Professor Harvey Moldofsky in 1975. Cyclobenzaprine is not associated with risk of addiction or dependence. The TNX-102 SL tablet is based on a eutectic formulation of cyclobenzaprine HCl and mannitol that provides a stable product which dissolves rapidly and delivers cyclobenzaprine by the transmucosal route efficiently into the bloodstream. The eutectic protects cyclobenzaprine HCl from interacting with the basifying agent that is also part of the formulation and required for efficient transmucosal absorption. Patents based on TNX-102 SL’s eutectic composition and its properties have issued in the U.S., E.U., Japan, China and many other jurisdictions around the world and provide market protection into 2034. The European Patent Office’s Opposition Division maintained Tonix’s European Patent EP 2 968 992 in unamended form after an Opposition was filed against it by a Sandoz subsidiary, Hexal AG. Hexal AG did not appeal that decision. The formulation of TNX-102 SL was designed specifically for sublingual administration and transmucosal absorption for bedtime dosing to target disturbed sleep, while reducing the risk of daytime somnolence. Clinical pharmacokinetic studies indicated that relative to oral cyclobenzaprine, TNX-102 SL results in higher levels of exposure during the first 2 hours after dosing and in deceased levels of the long-lived active metabolite, norcyclobenzaprine in both single dose and multiple dose studies, consistent with bypassing first pass hepatic metabolism. At steady state after 20 days of dosing TNX-102 SL, the dynamic peak level of cyclobenzaprine is higher than the background level of norcyclobenzaprine. In contrast, after 20 days of dosing oral cyclobenzaprine, the simulated peak level of cyclobenzaprine is lower than the simulated background level of norcyclobenzaprine. Tonix Pharmaceuticals Holding Corp. * Tonix is a fully integrated biopharmaceutical company focused on transforming therapies for pain management and vaccines for public health challenges. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to advance TNX-102 SL, a product candidate for the management of fibromyalgia. The FDA has accepted the NDA filing for TNX-102 SL for fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction and acute stress disorder under a Physician-Initiated IND at the University of North Carolina in the OASIS study funded by the U.S. Department of Defense (DoD). Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase), a biologic in Phase 2 development designed to treat cocaine intoxication that has FDA Breakthrough Therapy designation, and its development is supported by a grant from the U.S. National Institute of Drug Abuse and Addiction. Tonix’s immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is an Fc-modified 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, including TNX-2900 for Prader-Willi syndrome, and infectious disease, including a vaccine for mpox, TNX-801. In July 2024, Tonix announced a contract with the U.S. DoD’s Defense Threat Reduction Agency (DTRA) 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. 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; their efficacy and safety have not been established 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 www.tonixpharma.com. 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 market 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. Source: Tonix Pharmaceuticals Holding Corp. TNX-102 (cyclobenzaprine hydrochloride) FDA Approval History Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Maternal mortality in the U.S. has been on the rise, with the rate per 100,000 live births more than doubling from the first decade of the 2000s to the second.Health equity remains a major piece of the puzzle. As of 2022, Black women were more than twice as likely to die from a pregnancy-related condition than women of other racial backgrounds. This highlights shortcomings in access to care, but also points to the general lack of research in the field, said A. Metin Glmezoglu, executive director at the nonprofit Concept Foundation, which leads a project called Accelerating Innovation for Mothers.There have been very few new medicines being registered for these pregnancy conditions in the last 30 to 40 years, Glmezoglu said. If you compare this to innovations in other areas like chronic diseases, it's really tiny in terms of the number of solutions we have.The slow pace of innovation can be traced back to two major mid-20th century tragedies related to prescription drugs the nausea medicine thalidomide for pregnant women led to severe birth defects in thousands of children in the 1950s and 1960s and, not long after that, the hormone diethylstilbestrol was found to cause cancer in women who had been exposed to it in utero.These developments chilled drug research involving pregnant women. But in a twist of fate, what was meant to protect women and their children made it harder to find new drugs for them, Glmezoglu said, driving up mortality rates.These tragedies created this enormous fear and risk averseness in this area because those two drugs were not actually researched properly without a rigorous evaluation before, Glmezoglu said. That created this mindset that pregnant women are vulnerable and we have to protect the fetus, even if it means we have to withhold medication a woman might need.The research shortcomings are global, but they have a greater impact among women in low- and middle-income countries, where clinical research is less, Glmezoglu said.Other challenges include the limited time period of pregnancy, which makes drug testing more difficult. All of these combine for a perfect storm where nobody's investing in this field, he added.A gendered problemWhen women take part in clinical research and become pregnant, they are often taken out of that trial, Glmezoglu said, further thinning the data that becomes available.All of these differences tend to push evaluation to male bodies, male cell cultures and so on, which in the short term may be helpful because you can find solutions easier, but it doesn't help because you are not developing solutions for the other 50% of the population, Glmezoglu said.This was made clear during the COVID-19 pandemic, when vaccine trials excluded pregnant women, even though they were at higher risk of mortality and morbidity from the virus. That shifted the responsibility to healthcare providers and patients to decide whether to receive a shot.Gaining traction for a widespread push to study women's health issues more could partly hinge on winning political and public support.Inclusion of women and inclusion of pregnant and lactating women in trials has for many years been a secondary concern, Glmezoglu said. Any political process that does not support inclusivity and equality is likely to have an adverse effect on women's inclusion in research as a general concern.Mercks effortsJacquelyn Caglia, director of learning, communications and U.S. programs, Merck for MothersPermission granted by Merck for MothersOne success story came out of pharmaceutical giant Merck & Co. in 2018, which through its Merck for Mothers initiative studied the use of heat-stable carbetocin, finding it was not inferior to the standard of care oxytocin at preventing excessive bleeding after birth. The heat-stable nature of the new compound makes it easier to use in countries where refrigeration is difficult to come by.Merck for Mothers has been building evidence for maternal mortality trends since 2011 and providing women with education and health solutions in the U.S., India, Kenya and Nigeria. The initiative has reached more than 30 million women in that time, said Jacquelyn Caglia, director of learning, communications and U.S. programs at Merck for Mothers.Caglias vision is to see a healthcare system with a plan in place to treat mothers in the same way it treats newborns.What are our opportunities to think about mom and baby receiving care together? Our system across the U.S. is not quite set up that way, Caglia said. We have a very clear schedule for the types of care and visits and the timing of those visits that newborns need to have but what's our opportunity to think about mom and the care that they should be receiving alongside the newborn at those same points in time?Through programs like the Safer Childbirth Cities which supports community organizations in cities with high maternal mortality rates Merck for Mothers aims to meet mothers where they are, reducing geographic disparities that cause gaps in outcomes.We're still seeing in our national trends across the U.S. and globally, that most of the deaths, most of the complications, are preventable, which points us in the direction of where we need to intervene, Caglia said. There are continued patterns of differences based on race and ethnicity as well as based on geography ... and those disparities demand our attention. '