On August 9, 2021 Eagle Pharmaceuticals, Inc. (Nasdaq: EGRX) ("Eagle" or the "Company") reported that it has entered into a licensing agreement with AOP Orphan Pharmaceuticals GmbH ("AOP Orphan"), a privately owned Austrian company devoted to the treatment of rare and special diseases, for the commercial rights to its product, Landiolol in the United States (Press release, Eagle Pharmaceuticals, AUG 9, 2021, View Source [SID1234586137]). Landiolol, a leading hospital emergency use product, is currently approved in Europe for the treatment of non-compensatory sinus tachycardia and tachycardic supraventricular arrhythmias. The Company will support the submission of a new drug application ("NDA") to the U.S. Food and Drug Administration ("FDA") seeking approval for Landiolol for the short-term reduction of ventricular rate in patients with supraventricular tachycardia ("SVT"), including atrial fibrillation and atrial flutter.

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Landiolol is a short-acting, ultra-high selective beta-1 adrenoceptor blocker developed by AOP Orphan that has a selective effect on heart rate over cardiac contractility. Landiolol is available in two forms (20 mg/2ml concentrate, 300 mg powder) and is designed for use in emergency, cardiac critical care, operating room, and intensive care settings. It is registered in several European countries for the treatment of non-compensatory sinus tachycardia and tachycardic supraventricular arrhythmias. The drug uses a proprietary dosing algorithm to facilitate the administration.

Under the terms of the agreement, Eagle will facilitate the U.S. regulatory pathway for the approval of Landiolol. In addition, Eagle will be responsible for the U.S. commercialization of the product upon approval. Landiolol, which has not previously been marketed in the U.S., is covered by several patents, and the Company anticipates five years of new chemical entity ("NCE") exclusivity.

Landiolol is already commercially available in Japan (Onoact) and several European markets as RAPIBLOC. A review of multiple clinical studies suggests that Landiolol is a useful 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 Orphan 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. FDA tentatively agreed with this methodological approach and deemed data sets adequate to support a proposed NDA.

"This is an exciting near-term opportunity for Eagle, with the potential to file an NDA in the first quarter of next year. The clinical advantages of Landiolol are well recognized within the medical community, and we look forward to advancing this asset for FDA approval in the United States. Our deep understanding of the U.S. regulatory landscape, along with our established research and development infrastructure, will be valuable in accelerating the program. Once approved, we plan to leverage our current sales force and relationships in the critical care setting to promote the product. There is broad potential to expand the portfolio of future indications for Landiolol’s use," stated Scott Tarriff, Chief Executive Officer of Eagle Pharmaceuticals.

"With this license agreement, we are solidifying our hospital and critical care product portfolio, as we look to capitalize on multiple near- and longer-term opportunities. As we have stated, executing on our growth strategy for Eagle beyond 2021 has been a priority. With the anticipated launch of vasopressin, the February 2022 launch of PEMFEXY, the recent launch of bendamustine in Japan, our current pipeline, and now the future potential Landiolol launch, we believe we have a firm foundation for sustained future growth," concluded Tarriff.

"The step into the American market forms the basis for further expansion of AOP Orphan. I am convinced that with an experienced partner like Eagle, we will succeed in making Landiolol available to patients in the U.S. as well," stated Georg Fischer, Chief Executive Officer of AOP Orphan.

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

Landiolol has the potential to become a cornerstone therapy in the management of these patients. It is ultra short acting, with a rapid on and off effect that allows clinicians to balance heart rate control and blood pressure more precisely. In addition, it predominantly affects heart rate without much effect on cardiac contractility and blood pressure. 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 is under way in Europe for a trial of Landiolol in patients with tachycardia and septic shock, and importantly, the product is also being studied in a pediatric population, for whom no beta-blocker drug products are approved in the U.S. for ventricular rate control. The U.S. FDA has tentatively agreed that this study could form the basis for initial pediatric study plan ("iPSP") for a future submission to FDA.

"We believe that we can expedite and prepare a compelling submission for approval of this important cardioprotective therapeutic," stated Judith Ng-Cashin, MD, Chief Medical Officer of Eagle Pharmaceuticals

Terms of the Agreement

The agreement is subject to regulatory clearance. Under the terms of the agreement, Eagle will make an upfront payment of $5 million, followed by additional payments upon regulatory approval(s) and based upon commercial sales. The agreement is subject to regulatory clearance.