Eagle Pharmaceuticals Announces Submission of NDA to FDA for a Beta-1 Adrenergic Blocker

Eagle Pharmaceuticals, Inc. recently announced that AOP Orphan Pharmaceuticals GmbH, a member of the AOP Health Group, with whom Eagle entered into a licensing agreement in August 2021, submitted a new drug application (NDA) to the US FDA for landiolol, a short-acting, intravenous (IV), cardio-selective beta-1 adrenergic blocker. The submission seeks approval for landiolol for the short-term reduction of ventricular rate in patients with supraventricular tachycardia (SVT), including atrial fibrillation and atrial flutter.

“The submission of the landiolol NDA is a significant step forward for our company, as we look to bring this important therapeutic candidate to the US market and to expand our footprint in the acute care setting. We believe that landiolol has the potential to become a cornerstone therapy in the management of tachycardia in critically ill patients. Landiolol has differentiated clinical characteristics and an established safety profile, and we look forward to working with FDA during the course of the review process,” said Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals. “We are successfully diversifying our revenue stream, anticipated to grow from three commercial products just last year to eight upon the closing of the anticipated Acacia Pharma transaction, and nine with landiolol, if approved. We look forward to the potential of adding another strong product to our portfolio and to leveraging our highly capable hospital-based sales force.”

Landiolol is an ultra-short-acting, cardio-selective, beta-1 adrenoceptor blocker, which reduces heart rate and has a minimal effect over cardiac contractility (inotropy). Landiolol is designed for use in emergency, critical care, and operating room settings. It is registered in several European countries for the treatment of tachycardic supraventricular arrhythmias and non-compensatory sinus tachycardia.

Landiolol is already commercially available in Japan (Onoact) and several European markets as RAPIBLOC. Multiple clinical studies in these geographies demonstrate that landiolol is a safe and effective option for the rapid short-term control of tachyarrhythmias (Syed YY. Landiolol: A Review in Tachyarrhythmias. Drugs. 2018 Mar;78(3):377-388. doi: 10.1007/s40265-018-0883-9. PMID: 29470800.). A Type C meeting was held with FDA in July 2020, at which time AOP Health proposed a submission strategy in which it would provide summaries of pre-existing safety and efficacy data and a meta-analysis of published randomized controlled trials. The FDA tentatively agreed with this methodological approach and deemed data sets adequate to support a proposed NDA.

The management of rapid heart rate (tachycardia) in critically ill patients can be quite complicated regardless of the underlying cause. Beta blockers, also known as beta-adrenergic blocking agents, are a class of drugs that lower heart rate by blocking the neurotransmitters norepinephrine and epinephrine from binding to receptors. These neurotransmitters contribute to the development of tachycardia. β-1 receptor beta blockers are used frequently in critical care settings to manage tachycardia; however, the available β-1 beta blockers in the US can have the unwanted effects of decreasing the contractility, or muscle strength, of the heart, and of lowering blood pressure to a greater extent than landiolol.

Landiolol is ultra-short acting, with a rapid on and off effect that allows clinicians to quickly control heart rate with minimal impact on blood pressure. In addition, with a β1:β2 ratio of 255:1, landiolol is the most cardioselective beta blocker, which the Company believes will result in the least potential impact on respiratory function among available β-blockers. The Company believes that clinicians will welcome landiolol as a key therapeutic tool for the more precise management of tachycardia in the critical care setting.

There are additional clinical settings for which landiolol has the potential to improve patient management. Enrollment in LANDI-SEP, a European clinical trial studying landiolol in patients with tachycardia and septic shock, is complete. Importantly, landiolol is also being studied in a pediatric population, for whom no intravenous beta-blocker drug products are approved in the US for ventricular rate control. The FDA has tentatively agreed that this study could form the basis for proposed pediatric study plans for a future submission to FDA.

Eagle is a fully integrated pharmaceutical company with research and development, clinical, manufacturing, and commercial expertise. Eagle is committed to developing innovative medicines that result in meaningful improvements in patients’ lives. Eagle’s commercialized products include vasopressin injection, PEMFEXY, RYANODEX, BENDEKA, BELRAPZO, TREAKISYM (Japan), and its oncology and CNS/metabolic critical care pipeline includes product candidates with the potential to address underserved therapeutic areas across multiple disease states. For more information, visit www.eagleus.com.