Pharma Tech
Globenewswire | August 02, 2023
Tonix Pharmaceuticals Holding Corp. a biopharmaceutical company, announced that it has completed enrollment of its potentially final, confirmatory Phase 3 RESILIENT trial of TNX-102 SL (cyclobenzaprine HCL sublingual tablets) 5.6 mg in fibromyalgia and expects topline data next quarter. A total of 457 participants were randomized. TNX-102 SL is in development as a non-opioid, centrally acting analgesic, to be taken daily at bedtime for the management of fibromyalgia. If successful, we believe this will be the final, well-controlled efficacy trial required for submission of a New Drug Application (NDA) for approval by the U.S. Food and Drug Administration (FDA).
“The completion of enrollment in our Phase 3 RESILIENT trial is a significant milestone for both Tonix and the fibromyalgia community,” said Seth Lederman, M.D., Chief Executive Officer of Tonix. “Currently-approved treatments have not fully met the needs of fibromyalgia patients and there has not been a new FDA-approved therapy for the condition since 2009. TNX-102 SL has the potential to be a new non-addictive, non-opioid bedtime medication with broad spectrum symptom coverage and which can be used on a chronic basis for the management of fibromyalgia. With all other clinical, nonclinical and CMC requirements for an NDA submission achieved, we are looking forward to the upcoming data readout and an expeditious filing of an NDA.”
In December 2020, Tonix reported positive results from the first Phase 3 study (RELIEF) of TNX-102 SL 5.6 mg for the management of fibromyalgia. TNX-102 SL met its pre-specified primary endpoint in the Phase 3 RELIEF trial, significantly reducing daily pain compared to placebo (p=0.01) in participants with fibromyalgia. Also, when the primary endpoint was analyzed as a ≥30% pain responder analysis, there was a higher rate of responders to TNX-102 SL (47%) than to placebo (35%; p=0.006). TNX-102 SL at 5.6 mg also showed activity in key secondary endpoints demonstrating improvements in sleep quality, mitigation of fatigue, and fibromyalgia-specific global symptomatic and functional recovery. TNX-102 SL was generally safe and well tolerated in patients with fibromyalgia, with overall adverse event profile comparable to prior fibromyalgia studies. The most common treatment-emergent adverse events were oral hypoesthesia, oral paresthesia, and product taste abnormal.
About the Phase 3 RESILIENT Study
The RESILIENT study is a double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) in the management of fibromyalgia. The two-arm trial randomized 457 participants in the U.S. The first two weeks of treatment consist of a run-in period in which participants start on TNX-102 SL 2.8 mg (1 tablet) or placebo. Thereafter, all participants increase their dose to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks. The primary endpoint is the daily diary pain severity score change (TNX-102 SL 5.6 mg vs. placebo) from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation.
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 an estimated 6-12 million adults in the U.S., approximately 90% of whom are women. Symptoms of fibromyalgia include chronic widespread pain, nonrestorative sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety and depression. 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.
About TNX-102 SL
TNX-102 SL is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities at the 5-HT2A-serotonergic, α1-adrenergic, H1-histaminergic, and M1-muscarinic receptors, TNX-102 SL is in development as a daily bedtime treatment for fibromyalgia, Long COVID (formally known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder and agitation in Alzheimer’s disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic™ protective eutectic and Angstro-Technology™ formulation claimed in the patent are important elements of Tonix’s proprietary TNX-102 SL composition. These patents are expected to provide TNX-102 SL, upon NDA approval, with U.S. market exclusivity until 2034/2035.
Tonix Pharmaceuticals Holding Corp.
Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment in a potentially registration-enabling study, with topline data expected in the fourth quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 study has been completed, and topline results are expected in the third quarter of 2023.
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PHARMACY MARKET
businesswire | September 26, 2023
Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company focused on ADHD, pain, addiction and neurological disorders, today announced that Health Canada has authorized the use of Quillivant® ER (extended release) for the treatment of attention deficit hyperactivity disorder (ADHD) in children ages 6 to 12. Quillivant ER will be available as both an oral suspension and chewable tablet (known in the United States as Quillivant XR® and QuilliChew ER®, respectively). Quillivant ER is the first once-daily, long-acting, chewable and oral suspension formulations of methylphenidate to be approved for the treatment of ADHD in Canada.
“Children with ADHD around the world need medications that provide fast-acting and long-lasting relief in a range of formulations that are easy for them to take. Since the launch of our Quillivant XR product in the United States, we have been approached by potential partners to make our portfolio of ADHD products available around the world,” said Ketan Mehta, founder and chief executive officer at Tris Pharma. “We are truly delighted by this milestone, which will make this important medication available to millions of patients in Canada.”
Ontario-based KYE Pharmaceuticals, Inc. will make Quillivant ER Oral Suspension and Quillivant ER Chewable Tablets available to patients in Canada beginning in Q1 2024. Tris will manufacture Quillivant ER in the United States and export to KYE Pharmaceuticals for Canadian patients.
ADHD is one of the most common neurodevelopmental disorders diagnosed among children. Many therapies approved to treat ADHD have well-established and significant drawbacks, including early symptom rebound, limited duration of release and efficacy, delayed onset, inability to customize or control titration, and patient difficulty taking the medications (e.g., children unable to swallow a tablet).
In Canada, Quillivant ER is authorized for administration to children aged 6 to 12 diagnosed with ADHD as a once-daily liquid suspension or as a chewable tablet to overcome the difficulty of swallowing pills while still achieving the duration needed to control ADHD symptoms for the desired timeframe. Quillivant ER has demonstrated onset of action as soon as 45 minutes through 12 hours post-dose, providing consistent, continuous delivery throughout the day. Quillivant ER Oral Suspension allows for personalized dosing with ease of titration and the Quillivant ER chewable tablets are scored tablets, which are ideal for pediatric patients, providing additional flexibility in dose administration with the most dosing options available in an extended-release methylphenidate tablet. Tris developed both formulations using the company’s proprietary LiquiXR® technology.
“Quillivant ER has the potential to address a significant unmet market need in the treatment of ADHD by overcoming drawbacks associated with many other ADHD medications, particularly among children,” said John McKendry, president at KYE Pharmaceuticals. “Our strategic partnership with Tris allows us to apply our extensive regulatory and commercial expertise to ensure this unique ADHD medication is made available to patients in Canada.”
About Tris Pharma
Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain and neurological disorders, including addiction and diseases of the central nervous system. Tris is an established commercial organization with a robust portfolio of best-in-class ADHD products and a promising pipeline of differentiated, near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @TrisPharma.
About KYE Pharmaceuticals
Kye Pharmaceuticals Inc. is a private company headquartered in Mississauga, Canada focused on bringing medications to the Canadian market which fulfill clinically significant and unmet needs. KYE has licensed many innovative products and was founded on an entrepreneurial spirit that optimizes our team’s strengths and brings unique value to our partners, Canadian healthcare professionals, and most importantly, patients across Canada.
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Pharmacy Market
Globenewswire | August 14, 2023
Tonix Pharmaceuticals Holding Corp. a biopharmaceutical company, today announced the completion of the clinical phase of the Phase 2 proof-of-concept PREVAIL study of TNX-102 SL as a potential treatment for fibromyalgia-type Long COVID. Topline results for the PREVAIL study are expected in the third quarter of 2023.
“Approximately 40% of U.S. Long COVID patients have fibromyalgia-like multi-site pain symptoms based on our observational studies of Long COVID patients from the TriNetX claims database,”2,3 said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “In addition to multi-site pain, these individuals often suffer from one or more other symptoms typically associated with fibromyalgia such as fatigue, sleep disturbance, and brain fog. We have termed this subgroup, ‘Fibromyalgia-type Long COVID.’ Given our encouraging results with TNX-102 SL as a potential treatment for fibromyalgia4, we are testing TNX-102 SL as a bedtime medicine for the management of Fibromyalgia-type Long COVID. In completing this clinical milestone, marked by the last enrolled patient finishing their final visit, we can now begin to look forward to topline results from the 63-patient PREVAIL study later this quarter.”
Dr. Lederman continued, “TNX-102 SL improves sleep quality in fibromyalgia, and we believe this is the mechanism by which TNX-102 SL improves other symptoms, like multi-site pain.5 Recently, the U.S. National Institutes of Health (NIH) has identified improving sleep quality as a target for potential therapeutics for Long COVID6,7,8, consistent with the proposed mechanism of TNX-102 SL.
“Common symptoms of Long COVID, including multi-site pain, fatigue, unrefreshing sleep, and cognitive dysfunction, or ‘brain fog,’ are also hallmarks of conditions like fibromyalgia and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME),”9 said Herbert Harris, M.D., Ph.D., Executive Vice President and Head of Translational Medicine of Tonix Pharmaceuticals. “Defining subgroups of Long COVID patients that overlap with fibromyalgia and CFS/ME is expected to facilitate the development of new treatments.4 It can be challenging to distinguish fibromyalgia and CFS/ME clinically, given the high level of symptom overlap between them. Each of these conditions is defined by a constellation of symptoms, and there is no widely recognized diagnostic laboratory test that distinguishes them.”
Dr. Harris continued, “The recent identification of Long COVID subgroups in the National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored RECOVER study10 was an important step. In their recent publication, cluster analysis of the symptom frequencies in the RECOVER study identified four subgroups of Long COVID patients. Cluster #4 represented approximately one-quarter of the population (28%) and reported the highest frequencies of pain (back pain (58%), joint pain (64%) or muscle pain (60%)), high frequencies of fatigue (94%) and ’Brain Fog,’ (94%) and a high level of impairment of Quality of Life. We believe Cluster #4 is a subgroup of Long COVID that shares many clinical features with fibromyalgia and may involve common disease mechanisms. We also believe that Cluster #3, representing another approximately 29% of the RECOVER cohort, includes many patients with fibromyalgia-type Long COVID because 100% of that group suffer from ‘Brain Fog’, 94% experience fatigue and approximately one-third
experience pain (back pain (32%), joint pain (36%) or muscle pain (34%)).”
Dr. Harris concluded, “With no FDA approved treatment for Long COVID, we understand the need to better understand long COVID and to develop treatments for subgroups of this unserved population of patients. Fibromyalgia has been recognized by the U.S. Food and Drug Administration (FDA) with three approved medicines. Consequently, measuring daily pain is a validated endpoint for FDA registrational studies in fibromyalgia. We believe that daily pain has the potential to be an endpoint for registrational studies in fibromyalgia-like long COVID.”
About the Phase 2 PREVAIL Study
The Phase 2 PREVAIL study is a 14-week double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-102 SL taken daily at bedtime in patients with multi-site pain associated with post-acute sequelae of SARS-CoV-2 infection (PASC). The trial is being conducted at approximately 30 sites in the U.S. The primary efficacy endpoint will be the change from baseline in the weekly average of daily self-reported worst pain intensity scores at the Week 14 endpoint. Key secondary efficacy endpoints include change from baseline in self-reported scores for sleep disturbance, fatigue, and cognitive function. Topline results are expected in the third quarter of 2023.
About Long COVID or Post-Acute Sequelae of COVID-19 (PASC)
Post-acute sequelae of COVID-19, or PASC is the formal name for a condition now widely known as Long COVID. Although most people recover from COVID-19 within weeks of the acute illness, a substantial portion develops a chronic syndrome called Long COVID.11 These individuals experience a constellation of disabling symptoms long past the time of recovery from acute COVID-19. Most Long COVID patients who have been studied appear to have cleared the SARS-CoV-2 infection from their systems. The symptoms of Long COVID can include fatigue, sleep disorders, multi-site pain, fevers, shortness of breath, cognitive impairment described as “brain fog” or memory disturbance, gastrointestinal symptoms, anxiety, and depression. According to the Centers for Disease Control and Prevention (CDC), 1 in 13 adults in the U.S. (7.5%) have Long COVID symptoms.1 Long COVID is typically associated with moderate or severe COVID-19, but can occur after mild COVID-19 or even after asymptomatic SARS-CoV-2 infection. More than 40% of adults in the United States reported having COVID-19 in the past, and nearly one in five of those (19%) are currently still having symptoms of Long COVID.1 Long COVID is a chronic disabling condition that is expected to result in a significant global health and economic burden.12-15
About TNX-102 SL
TNX-102 SL is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities at the 5-HT2A-serotonergic, α1-adrenergic, H1-histaminergic, and M1-muscarinic receptors, TNX-102 SL is in development as a daily bedtime treatment for fibromyalgia, Long COVID (formally known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder and agitation in Alzheimer’s disease.
AboutTonix Pharmaceuticals Holding Corp.
Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in the fourth quarter of 2023.
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