Eagle Pharmaceuticals announced that AOP Orphan Pharmaceuticals GmbH has submitted a new drug application (NDA) to the U.S. Food and Drug Administration for landiolol, a short-acting, intravenous, 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.
Unique Pharmacological Profile
Landiolol is an ultra-short-acting, cardio-selective, beta-1 adrenoceptor blocker that reduces heart rate while having minimal effect on cardiac contractility (inotropy). The drug is designed specifically for use in emergency, critical care, and operating room settings. With a β1:β2 ratio of 255:1, landiolol is the most cardioselective beta blocker, which Eagle believes will result in the least potential impact on respiratory function among available β-blockers.
The ultra-short acting nature of landiolol provides a rapid on and off effect that allows clinicians to quickly control heart rate with minimal impact on blood pressure. This distinguishes it from available β-1 beta blockers in the U.S., which can have unwanted effects of decreasing heart contractility and lowering blood pressure to a greater extent than landiolol.
Established International Presence
Landiolol is already commercially available in Japan under the brand name Onoact and in several European markets as RAPIBLOC. It is registered in several European countries for the treatment of tachycardic supraventricular arrhythmias and non-compensatory sinus tachycardia. Multiple clinical studies in these geographies demonstrate that landiolol is a safe and effective option for the rapid short-term control of tachyarrhythmias.
Regulatory Strategy and Timeline
A Type C meeting was held with the FDA in July 2020, during which AOP Health proposed a submission strategy involving 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 the data sets adequate to support the proposed NDA.
Based on feedback from the FDA provided during the Type C meeting, Eagle expects approval by mid-year 2023, if the application is accepted for filing. If landiolol is approved, Eagle expects five years of new chemical entity exclusivity.
Clinical Need and Market Opportunity
The management of rapid heart rate (tachycardia) in critically ill patients can be complicated regardless of the underlying cause. Beta blockers are used frequently in critical care settings to manage tachycardia by blocking neurotransmitters norepinephrine and epinephrine from binding to receptors, as these neurotransmitters contribute to tachycardia development.
"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 U.S. market and to expand our footprint in the acute care setting," stated Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals. "We believe that landiolol has the potential to become a cornerstone therapy in the management of tachycardia in critically ill patients."
Expanding Clinical Applications
There are additional clinical settings for which landiolol has 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 U.S. 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.
Portfolio Expansion
Tarriff noted the company's successful revenue diversification strategy: "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."
