Business Insights, PHARMA TECH
PRNewswire | July 19, 2023
Endo International plc announced that its Par Sterile Products business has begun shipping bivalirudin injection in a ready-to-use 250 mg/50 mL single-use vial. It is the only ready-to-use liquid format of bivalirudin on the market in the U.S.
"Hospital practitioners work hard to provide quality patient care while also meeting operational challenges," said Scott Sims, Senior Vice President and General Manager, Injectable Solutions & Generics at Endo. "With ready-to-use products like bivalirudin, we're helping to deliver solutions that reduce complexity for healthcare providers—so they can focus on patient care."
In May 2023, Endo executed agreements with MAIA Pharmaceuticals, Inc. and Gland Pharma Limited, India to commercialize ready-to-use bivalirudin in the U.S. The product, manufactured by Gland Pharma Limited, is an anticoagulant (thrombin inhibitor) that helps prevent the formation of blood clots. It is used to prevent blood clots in people with severe chest pain or other conditions who are undergoing an angioplasty procedure.
Ready-to-use, or RTU, products streamline operations for hospitals by eliminating the need to prepare or transfer the product before patient administration. This may reduce waste and costs, optimize convenience and workflow and reduce the chance for preparation error—all of which support quality patient care
In clinical trials in patients undergoing percutaneous coronary intervention (PCI), co-administration of bivalirudin with heparin, warfarin, thrombolytics, or GPls was associated with increased risks of major bleeding events compared to patients not receiving these concomitant medications.
USE IN SPECIFIC POPULATIONS
In studies of patients undergoing PCI, 44% were ≥65 years of age and 12% of patients were ≥75 years old. Elderly patients experienced more bleeding events than younger patients.
The disposition of bivalirudin was studied in PTCA patients with mild, moderate and severe renal impairment. The clearance of bivalirudin was reduced approximately 21% in patients with moderate and severe renal impairment and was reduced approximately 70% in dialysis- dependent patients. The infusion dose of bivalirudin injection may need to be reduced, and anticoagulant status monitored in patients with renal impairment.
INDICATION AND USAGE
Bivalirudin injection is indicated for use as an anticoagulant in patients undergoing PCI, including patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis syndrome.
Endo is a specialty pharmaceutical company committed to helping everyone we serve live their best life through the delivery of quality, life-enhancing therapies. Our decades of proven success come from passionate team members around the globe collaborating to bring treatments forward. Together, we boldly transform insights into treatments benefiting those who need them, when they need them.
PRNewswire | July 18, 2023
Karyopharm Therapeutics Inc. a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation to the development program of selinexor for the treatment of patients with myelofibrosis, including primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis.
"Fast Track Designation for selinexor highlights its potential to address the unmet medical need in myelofibrosis, an important acknowledgement as we continue our pivotal Phase 3 study," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "Selinexor's unique mechanism of action, XPO1 inhibition, is a novel and potentially fundamental mechanism in myelofibrosis. We have been highly encouraged by the efficacy and safety data observed to date [in our Phase 1 study] with selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis and believe selinexor has the potential to shift the treatment paradigm. We look forward to continued interaction with the FDA as we advance the development of this promising treatment for patients in need."
In June 2023, Karyopharm initiated a pivotal Phase 3 clinical trial to assess the efficacy and safety of once-weekly selinexor 60 mg in combination with ruxolitinib in JAKi-naïve patients with myelofibrosis. Updated data from the Phase 1 study were presented at the American Association for Cancer Research Annual Meeting 2023, American Society of Clinical Oncology 2023 and European Hematology Association 2023, which showed rapid, deep and sustained spleen responses and robust symptom improvement in patients treated with selinexor 60 mg in combination with ruxolitinib as of the April 10, 2023 cut-off date. Top-line data from the Phase 3 study is expected in 2025. The Company plans to expand its clinical development program in myelofibrosis by investigating selinexor in other JAKi-naïve settings, such as novel combinations, to benefit the greatest number of patients.
Fast Track Designation is intended to facilitate development and expedite review of drugs to treat serious and life-threatening conditions so that an approved product can reach the market expeditiously. Features of Fast Track Designation include frequent interactions with the FDA review team, and if relevant criteria are met, eligibility for Priority Review and Rolling Review.
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. is a commercial-stage pharmaceutical company pioneering novel cancer therapies. Since its founding, Karyopharm has been an industry leader in oral Selective Inhibitor of Nuclear Export (SINE) compound technology, which was developed to address a fundamental mechanism of oncogenesis: nuclear export dysregulation. Karyopharm's lead SINE compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications and has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including Europe and the United Kingdom (as NEXPOVIO®) and China. Karyopharm has a focused pipeline targeting multiple high unmet need cancer indications, including in multiple myeloma, endometrial cancer, myelodysplastic neoplasms and myelofibrosis.
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.
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.