PRNewswire | August 04, 2023
Ionis Pharmaceuticals, Inc. announced that it has entered a collaboration and license agreement with Novartis for the discovery, development and commercialization of a novel medicine for patients with lipoprotein(a), or Lp(a)-driven cardiovascular disease (CVD). This builds on the companies' existing collaboration focused on the development and commercialization of pelacarsen, which Novartis is currently evaluating in a Phase 3 cardiovascular outcome study. The next generation compound will be a potential follow-on to pelacarsen.
"We are pleased to expand our productive collaboration with Novartis aimed at delivering transformative therapies to patients with elevated Lp(a) who are at high risk of cardiovascular events," said Brett P. Monia, Ph.D., Ionis' chief executive officer. "This collaboration is designed to leverage Ionis' advancing RNA-targeting platform technologies to deliver a novel Lp(a)-targeting therapy that we expect will provide industry-leading efficacy and dosing frequency."
Ionis will receive a $60 million upfront payment from Novartis and is eligible to earn development, regulatory and commercial milestone payments and tiered royalties. Novartis will be solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) therapy.
The agreement is subject to the satisfaction of requirements of the Hart-Scott-Rodino Antitrust Improvements Act of 1976.
Lp(a) is a lipoprotein particle assembled in the liver that consists of a low-density lipoprotein cholesterol (LDL-C)-like particle and apolipoprotein(a). Lp(a) levels in the blood can vary greatly between individuals primarily due to genetic variations and do not correlate with LDL-C levels. Even patients with LDL-C lowered to target levels (<70 mg/dL) remain at high-risk of cardiovascular events if they have high levels of Lp(a). Elevated Lp(a) is a genetically determined condition that is not responsive to lifestyle changes, therefore patients are unable to adequately control their Lp(a) levels through improved diet or increased physical activity. Elevated Lp(a) is recognized as an independent, genetic cause of coronary artery disease, heart attack, stroke, peripheral arterial disease and aortic stenosis. Currently, there is no effective drug therapy to specifically and robustly lower elevated levels of Lp(a).
Pelacarsen was discovered by Ionis and licensed to Novartis in 2019 for exclusive worldwide development, manufacturing and commercialization. It is an investigational antisense medicine designed to reduce apolipoprotein(a) production in the liver to offer a direct approach for reducing circulating Lp(a). It is estimated that more than eight million people worldwide have elevated Lp(a) and CVD.
Pelacarsen is currently being evaluated in Lp(a) HORIZON (NCT04023552), a global, multicenter, double-blind, placebo-controlled pivotal Phase 3 study conducted by Novartis. The study completed enrollment with 8,323 participants. Data are expected in 2025.
About Ionis Pharmaceuticals, Inc.
For more than 30 years, Ionis has been a leader in RNA-targeted therapy, pioneering new markets and changing standards of care. Ionis currently has four marketed medicines and a promising late-stage pipeline highlighted by cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision to become the leader in genetic medicine, utilizing a multi-platform approach to discover, develop and deliver life-transforming therapies.
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.
PHARMACY MARKET, PHARMA TECH
Businesswire | July 12, 2023
Kindeva Drug Delivery, a global leader in contract drug delivery development and manufacturing services and technology, and H&T Presspart (a division of the Heitkamp & Thumann Group), a market leader in respiratory drug delivery systems design, development, and manufacturing, are partnering with Chiesi Group, an international research-focused biopharmaceutical and healthcare group, for the installation of a production line for dose counter (DC) and dose indicator (DI) devices. Combining the specific expertise of each partner, H&T Presspart will manufacture Kindeva Drug Delivery’s dose counters under license for Chiesi Group for their pressurized metered-dose inhaler (pMDI) portfolio.
This partnership is a continuation of the agreement signed in 2014 between Kindeva Drug Delivery and H&T Presspart to accelerate the growth of Kindeva Drug Delivery’s dose counter technology. This technology enhances patient safety by providing real-time information on the remaining doses in inhalers, preventing unexpected shortages. H&T Presspart will expand the cleanroom facilities at their Marsberg, Germany, site to support the dose counter production. As part of this strategic partnership, Chiesi Group will use dose counters in their innovative carbon minimal pMDI portfolio, which uses a low Global Warming Potential (GWP) propellant to minimize the climate impact of the inhalers, while maintaining all the therapeutic options that patients suffering from respiratory diseases need.
David Stevens, global chief commercial officer of Kindeva Drug Delivery, stated: “Kindeva is pleased to extend this strategic partnership as it solidifies our core objective of improving the lives of patients around the world. Kindeva embraces the responsibility it has in ensuring that patients who depend upon our device technology are reliably supplied, and we believe that this innovative supply chain collaboration further underscores this commitment.”
Roberto Della Valle, head of global direct procurement of Chiesi Group, added: “Chiesi, with its patient-centric approach, is dedicated to delivering therapeutic solutions that enhance patients’ health and quality of life. Collaborating with Kindeva and H&T Presspart exemplifies this commitment, and we are thrilled to take this step forward. By providing an inhaler that reassures patients about the remaining dose count, we aim to enhance their safety and confidence.”
Christian Kraetzig, president of H&T Presspart, commented: “With our expertise in device industrialization and manufacturing, this agreement marks another step in our journey to becoming a leading development and contract manufacturing partner in drug delivery devices.”
About Kindeva Drug Delivery
Kindeva Drug Delivery is a global contract development manufacturing organization focused on drug-device combination products. Kindeva Drug Delivery develops and manufactures products across a broad range of complex drug-delivery formats, including injectables (autoinjector, intradermal, microneedle), pulmonary & nasal, and transdermal patches. Its service offering spans early-stage feasibility through commercial scale drug product fill-finish, container closure system manufacturing, and drug-device product assembly. Kindeva Drug Delivery serves a global client base from its nine manufacturing and research and development facilities located in the U.S. and U.K.
About Chiesi Group
Chiesi is an international, research-focused biopharmaceuticals group that develops and markets innovative therapeutic solutions in respiratory health, rare diseases, and specialty care. The company’s mission is to improve people’s quality of life and act responsibly towards both the community and the environment. By changing its legal status to a Benefit Corporation in Italy, the US, and France, Chiesi’s commitment to create shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, we’re part of a global community of businesses that meet high standards of social and environmental impact. The company aims to reach Net-Zero greenhouse gases (GHG) emissions by 2035. With over 85 years of experience, Chiesi is headquartered in Parma (Italy), operates in 31 countries, and counts more than 6,500 employees.