The US FDA approves AOP Health's Rapiblyk TM (landiolol) for the treatment of atrial fibrillation and atrial flutter in critical care

VIENNA-AOP Orphan Pharmaceuticals GmbH (AOP Health), based in Vienna, Austria, announced that it has received regulatory approval from the U.S. Food and Drug Administration (FDA) for Rapiblyk ^TM (landiolol) for the treatment of the serious heart condition supraventricular tachycardia (atrial fibrillation and atrial flutter) in intensive care. The approval was based on clinical studies that demonstrated that Rapiblyk ^TM (landiolol) enables rapid regulation of heart rate with minimal reduction in blood pressure. The approval provides patients in the United States with a new treatment option and marks an important step for AOP Health in fulfilling its mission to help patients and contribute to the fight against rare diseases and intensive care medicine in the United States.

Approval was based on data from five randomized, double-blind, placebo-controlled studies. A total of 317 adults with supraventricular tachycardia were treated with landiolol: In 40-90% of the treated patients, the heart rate decreased within about 10 minutes. In patients who received a placebo, the heart rate decreased in 0-11% of the patients. A reduction in heart rate was defined as a reduction of >20% or a heart rate <100 bpm or at least a temporary cessation of the arrhythmia. In placebo-controlled clinical studies, side effects were observed in 9.9% of patients treated with landiolol, compared to only 1% of patients treated with placebo.

New therapeutic option for rapid and “short-term” treatment of supraventricular tachycardia

AOP Health is committed to providing solutions for patients with rare diseases or in intensive care. This approval therefore marks an important milestone for patients in intensive care who suffer from atrial fibrillation or atrial flutter. “The approval of Rapiblyk ^TM in the USA is an important milestone for patients who suffer from supraventricular tachycardia, including atrial fibrillation and atrial flutter, and who require a rapid and short-term reduction in heart rate. We are very pleased that this treatment option, which is already available in Europe, is now also available to patients in the USA,” said Dr. Martin Steinhart, CEO of AOP Health.

Study design

Five randomized, double-blind, placebo-controlled studies were conducted to investigate the efficacy and safety of landiolol in patients with supraventricular tachycardia (including atrial fibrillation and atrial flutter). A total of 317 adults were treated with landiolol: the heart rate of patients treated with landiolol decreased by 40-90% compared to 0-11% in patients receiving placebo. A reduction in heart rate was defined as a decrease of >20% or a heart rate <100 bpm or at least a temporary cessation of the arrhythmia. The infusion dose of landiolol in these studies ranged from 9.3 to 74.6 µg/kg/min. Adverse reactions were observed in 9.9% of patients treated with landiolol (the most common adverse reaction was hypotension) compared to 1% of patients treated with placebo.

About supraventricular tachycardias

Supraventricular tachycardias (including atrial fibrillation and atrial flutter) can occur in patients with or without existing heart disease. Because they impair cardiac function and can lead to acute cardiovascular problems, they require immediate medical treatment.

About Rapiblyck ^TM (landiolol) intravenously [280 mg landiolol (equivalent to 300 mg landiolol HCl) in a single dose ampoule]

Landiolol is an ultra-short-acting adrenergic receptor antagonist with a beta-1/beta-2 selectivity ratio of 255. Landiolol is characterized by a rapid onset of action and a rapid reduction in heart rate without significantly lowering blood pressure. Landiolol was developed for use in emergency situations, in cardiac intensive care units, in the operating room and in intensive care units. It is used in emergency situations and for short-term treatment in intensive care. It is therefore not suitable for the treatment of chronic cardiac arrhythmias. In Europe, it is approved for the treatment of supraventricular tachycardia, including atrial fibrillation or atrial flutter, and for the treatment of non-compensatory sinus tachycardia.

INDICATION

RAPIBLYK ^TM is indicated for the short-term reduction of ventricular rate in adults with supraventricular tachycardia, including atrial fibrillation and atrial flutter.

IMPORTANT SAFETY INSTRUCTIONS

CONTRAINDICATIONS

RAPIBLYK ^TM is contraindicated in patients with:

· Severe sinus bradycardia, sick sinus syndrome, heart block greater than 1st degree

· Decompensated heart failure

Cardiogenic shock: Further cardiovascular collapse and cardiac arrest may occur.

Pulmonary hypertension: Cardiorespiratory decompensation may occur.

Hypersensitivity reactions, including anaphylaxis, to landiolol or any of the inactive ingredients

WARNINGS AND PRECAUTIONS

· Hypotension. There is an increased risk of hypotension in patients with hemodynamic compromise, hypovolemia, or drug interactions.

· Bradycardia. Patients with first degree AV block, sinus node dysfunction, or conduction abnormalities are at increased risk for bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest.

· Heart failure. Beta-blockers such as RAPIBLYK ^TM can impair myocardial contractility and induce heart failure and cardiogenic shock.

· Reactive airway disease. Patients with reactive airway disease should generally not receive beta-blockers. Due to its relative beta-1 selectivity and titratability, RAPIBLYK ^TM injection can be titrated to the lowest possible effective dose. If bronchospasm occurs, the infusion must be stopped immediately. A beta-2 stimulant may be administered with appropriate monitoring of ventricular rates.

· Treatment of patients with diabetes mellitus and hypoglycaemia. Beta-blockers may prevent early warning signs of hypoglycaemia, such as tachycardia, and may increase the risk of severe or prolonged hypoglycaemia at any time during treatment, particularly in patients with diabetes mellitus, in fasting patients (ie during surgery, irregular feeding or vomiting) or in children.

· Reactions at the infusion site. Reactions at the infusion site such as pain, swelling and redness have occurred with the administration of RAPIBLYK ^TM injections. Avoid infusions into small veins or through a butterfly catheter.

· Use in patients with Prinzmetal’s angina. Beta-blockers may worsen angina attacks in patients with Prinzmetal’s angina due to alpha-receptor-mediated vasoconstriction of the coronary arteries.

· Use in patients with pheochromocytoma. When administering RAPIBLYK ^TM injections in the setting of pheochromocytoma, RAPIBLYK should be administered in combination with an alpha-blocker and only after initiation of alpha-blocker therapy. Administration of beta-blockers without concurrent alpha-blockade in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure, which is due to attenuation of beta-receptor-mediated vasodilation in skeletal muscle.

· Use in patients with peripheral circulatory disorders. RAPIBLYK ^TM injection may lead to a worsening of peripheral circulatory disorders such as Raynaud’s disease or Raynaud’s syndrome and peripheral arterial occlusive disease.

· Abrupt discontinuation of RAPIBLYK ^TM injections. In patients with coronary artery disease, severe exacerbations of angina pectoris, myocardial infarction and ventricular arrhythmias have been reported following abrupt discontinuation of beta-blocker therapy.

· Hyperkalemia. Beta-blockers, including RAPIBLYK ^TM injection, may cause an increase in serum potassium levels and hyperkalemia. This risk is increased in patients with risk factors such as renal impairment. Potentially life-threatening hyperkalemia has been reported in hemodialysis patients caused by the intravenous administration of beta-blockers. Monitor serum electrolytes during therapy with RAPIBLYK ^TM injection.

· Use in patients with metabolic acidosis. Beta-blockers have been reported to cause hyperkalaemic renal tubular acidosis. Acidosis may generally be associated with reduced cardiac contractility.

· Use in patients with hyperthyroidism. Beta-adrenergic blockade may mask certain clinical signs (e.g. tachycardia) of hyperthyroidism. Abrupt discontinuation of beta-blockade may result in thyrotoxic shock. Patients should therefore be monitored for signs of thyrotoxicosis during discontinuation of beta-blocker therapy.

– Use in patients at risk for severe acute hypersensitivity reactions. Patients at risk for anaphylactic reactions may be more sensitive to allergen exposure (accidental, diagnostic or therapeutic) when using beta-blockers. Patients taking beta-blockers may not respond to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions.

SIDE EFFECTS

The most important and common side effect is hypotension, which occurred in clinical trials in 9.9% of patients receiving RAPIBLYK ^TM compared to 1% of patients receiving placebo.

Please see the full prescribing information for Rapiblyk ^TM (landiolol) at https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217202s000lbl.pdf

About AOP Health

The AOP Health Group comprises several companies, including AOP Orphan Pharmaceuticals GmbH, based in Vienna, Austria (“AOP Health”). The AOP Health Group is the European pioneer in integrated therapies for patients with rare diseases and in intensive care medicine. Over the last 25 years, the group has developed into an established provider of integrated therapy solutions, operating from its headquarters in Vienna, its subsidiaries and representative offices throughout Europe and the Middle East, and through partners worldwide. The claim “Needs. Science. Trust.” sums up the basis of success: creating trust through continuous high investments in research and development and a very consistent and pragmatic focus on the needs of all stakeholders – especially patients and their relatives as well as the treating doctors and nurses.

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