U.S. FDA Approves AOP Health’s RapiblykTM (landiolol) for Atrial Fibrillation and Atrial Flutter in the Critical Care Setting

VIENNA--(BUSINESS WIRE)--Nov 27, 2024--

AOP Orphan Pharmaceuticals GmbH (AOP Health), based in Vienna, Austria, announced that the U.S. Food and Drug Administration (FDA) has granted regulatory approval for Rapiblyk TM (landiolol) in the hospital critical care setting for the treatment of the severe heart condition supraventricular tachycardia (atrial fibrillation and atrial flutter). The approval is based on clinical studies which demonstrated that Rapiblyk TM (landiolol) enables rapid management of the heart rate with minimal reduction of blood pressure. The approval will provide patients in the U.S. with a new treatment option and is an important step for AOP Health in bringing its mission to help patients and make an impact on rare diseases and critical care to the United States for the first time.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20241127506170/en/

The approval was based on data of 5 randomized, double-blind, placebo-controlled studies. A total of 317 adults with supraventricular tachycardia were treated with landiolol: The heart rate decreased in 40-90% of treated patients within about 10 minutes, compared to 0-11% of patients who received placebo; heart rate decrease was defined as a >20% decrease in heart rate or a heart rate <100 bpm or at least intermittent cessation of the arrhythmia. In placebo-controlled clinical trials, adverse events were observed in 9,9% of landiolol treated patients vs. 1 % in patients treated with placebo.”

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

AOP Health strives to offer solutions for patients with rare diseases or in critical care. Therefore, this approval marks an important moment for patients suffering from atrial fibrillation and atrial flutter in intensive care settings. “Rapiblyk TM approval in the US represents an important milestone for patients experiencing supraventricular tachycardia, including atrial fibrillation and atrial flutter, who need rapid and short-term heart rate reduction. After being available in Europe, we are delighted that this therapeutic option can be now available also for US patients” says Dr. Martin Steinhart, CEO of AOP Health.

Study Design

Five randomized, double-blind, placebo-controlled studies were conducted to test landiolol efficacy and safety in patients with supraventricular tachycardia (including atrial fibrillation and atrial flutter). A total of 317 adults were treated with landiolol: heart rate in patients treated with landiolol decreased of 40-90% vs 0-11% of patients who received placebo. Heart rate decrease was defined as a >20% decrease in heart rate or a heart rate <100 bpm or at least intermittent cessation of the arrhythmia. The infused dose of landiolol in these studies ranged from 9.3 to 74.6 mcg/kg/min. Adverse events were observed in 9,9% of landiolol treated patients (main adverse event was hypotension) vs. 1 % in patients treated with placebo.”

About supraventricular tachycardias

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

About Rapiblyck TM (landiolol) intravenous [280 mg of landiolol (equivalent to 300 mg of landiolol HCl) in a single-dose vial]

Landiolol is an ultra-short-acting adrenergic receptor antagonist, with beta 1/beta 2 selectivity ratio of 255. Landiolol is characterized by a fast onset of action and rapid reduction in heart rate without significantly lowering blood pressure. It is designed for use in emergency, cardiac critical care unit, operating room, and intensive care settings. It is used in emergency conditions and for short term treatments in critical care. It is therefore not intended for the treatment of chronic cardiac arrhythmias. It is registered in Europe for the treatment of supraventricular tachycardia, including atrial fibrillation or atrial flutter and for the management 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 INFORMATION

CONTRAINDICATIONS

RAPIBLYK TM is contraindicated in patients with:

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

· Decompensated heart failure

· Cardiogenic shock: May precipitate further cardiovascular collapse and cause cardiac arrest.

· Pulmonary hypertension: May precipitate cardiorespiratory decompensation.

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

WARNINGS AND PRECAUTIONS

· Hypotension. Patients with hemodynamic compromise, hypovolemia, or on interacting medications are at increased risk of hypotension.

· Bradycardia. Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders are at increased risk of bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest.

· Cardiac Failure. Beta-blockers, like RAPIBLYK TM, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock.

· Reactive Airways Disease. Patients with reactive airways disease should, in general, not receive beta-blockers. Because of its relative beta-1 selectivity and titratability, RAPIBLYK TM injection may be titrated to the lowest possible effective dose. In the event of bronchospasm, stop the infusion immediately; a beta-2 stimulating agent may be administered with appropriate monitoring of ventricular rates.

· Use in Patients with Diabetes Mellitus and Hypoglycemia. Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus, patients who are fasting (i.e., surgery, not eating regularly, or are vomiting), or children.

· Infusion Site Reactions. Infusion site reactions such as pain, swelling and erythema have occurred with the use of RAPIBLYK TM injection. Avoid infusions into small veins or through a butterfly catheter.

· Use in Patients with Prinzmetal’s Angina. Beta-blockers may exacerbate anginal attacks in patients with Prinzmetal’s angina because of unopposed alpha receptor–mediated coronary artery vasoconstriction.

· Use in Patients with Pheochromocytoma. If RAPIBLYK TM injection is used in the setting of pheochromocytoma, administer RAPIBLYK in combination with an alpha-blocker, and only after the alpha-blocker has been initiated. Administration of beta-blockers without opposing alpha blockade in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure from the attenuation of beta receptor-mediated vasodilation in skeletal muscle.

· Use in Patients with Peripheral Circulatory Disorders. RAPIBLYK TM injection may exacerbate peripheral circulatory disorders, such as Raynaud’s disease or syndrome, and peripheral occlusive vascular disease.

· Abrupt Discontinuation of RAPIBLYK TM Injection. Severe exacerbations of angina, myocardial infarction, and ventricular arrhythmias have been reported in patients with coronary artery disease upon abrupt discontinuation of beta-blocker therapy.

· Hyperkalemia. Beta-blockers, including RAPIBLYK TM injection, can cause increases in serum potassium and hyperkalemia. The risk is increased in patients with risk factors such as renal impairment. Intravenous administration of betablockers has been reported to cause potentially life-threatening hyperkalemia in hemodialysis patients. Monitor serum electrolytes during therapy with RAPIBLYK TM injection.

· Use in Patients with Metabolic Acidosis. Beta-blockers have been reported to cause hyperkalemic renal tubular acidosis. Acidosis in general may 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 withdrawal of beta blockade might precipitate thyroid storm; therefore, monitor patients for signs of thyrotoxicosis when withdrawing beta blocking therapy.

- Use in Patients at Risk of Severe Acute Hypersensitivity Reactions. When using beta-blockers, patients at risk of anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic, or therapeutic). Patients using beta-blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions.

ADVERSE REACTIONS

The most important and common adverse reaction is hypotension, which in clinical trials occurred in 9.9% of patients receiving RAPIBLYK TM vs. 1% in those receiving placebo.

Please see the full Prescribing Information for Rapiblyk TM (landiolol), athttps://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217202s000lbl.pdf

About AOP Health

The AOP Health Group incorporates several companies including AOP Orphan Pharmaceuticals GmbH with its seat in Vienna, Austria (“AOP Health”). The AOP Health Group is the European pioneer for integrated therapies for rare diseases and in critical care. Over the past 25 years, the Group has become an established provider of integrated therapy solutions operating from its headquarters in Vienna, its subsidiaries and representative offices throughout Europe and the Middle East, as well as through partners worldwide. The claim “Needs. Science. Trust.” sums up the foundation of the Group’s success: establishing trust through a continually high level of investment in research and development and a highly consistent and pragmatic orientation towards the needs of all stakeholders – especially the patients and their families as well as the healthcare professionals treating them.

Portrait of Dr. Martin Steinhart, CEO AOP Health (Photo: AOP Health/Studio Koekart)

TYRE, Lebanon (AP) — A ceasefire between Israel and the Lebanese militant group Hezbollah that began Wednesday appeared to be holding, as residents in cars heaped with belongings streamed back toward southern Lebanon despite warnings from the Israeli and Lebanese militaries that they stay away from certain areas.

If it holds, the ceasefire would bring an end to nearly 14 months of fighting between Israel and Hezbollah, which escalated in mid-September into all-out war and threatened to pull Hezbollah's patron Iran and Israel into a broader conflagration. The deal does not address the war in Gaza.

It could give some reprieve to the 1.2 million Lebanese displaced by the fighting and the tens of thousands of Israelis who fled their homes along the border with Lebanon.

“They were a nasty and ugly 60 days,” said Mohammed Kaafarani, 59, who was displaced from the Lebanese village of Bidias. “We reached a point where there was no place to hide."

The U.S.- and France-brokered deal, approved by Israel late Tuesday, calls for an initial two-month halt to fighting and requires Hezbollah to end its armed presence in southern Lebanon, while Israeli troops are to return to their side of the border.

Thousands of additional Lebanese troops and U.N. peacekeepers would deploy in the south, and an international panel headed by the United States would monitor compliance.

Israel says it reserves the right to strike Hezbollah should it violate the terms of the deal.

Israel is still fighting Hamas militants in Gaza in response to the group’s cross-border raid into southern Israel in October 2023. But President Joe Biden on Tuesday said his administration would make another push in the coming days to try to renew efforts for a deal in the war-ravaged Palestinian enclave.

On the highway linking Beirut with south Lebanon, hours after the Israel-Hezbollah ceasefire took hold, thousands of people drove south with their belongings and mattresses tied on top of their cars. Traffic was gridlocked at the northern entrance of the port city of Sidon.

“This is a moment of victory, pride and honor for us, the Shiite sect, and for all of Lebanon,” said Hussein Sweidan, a resident returning to the port city of Tyre. He said he saw the ceasefire as a victory for Hezbollah.

Sporadic celebratory gunfire was heard at a main roundabout in the city, as people returning honked the horns of their cars and residents cheered.

Israel’s Arabic military spokesperson Avichay Adraee warned displaced Lebanese not to return to evacuated villages in southern Lebanon. Israeli troops were still present in parts of southern Lebanon after Israel launched a ground invasion in October. The Israeli military said forces opened fire to push back a number of vehicles that were entering a restricted area in southern Lebanon.

An Israeli security official said Israeli forces remain in their positions hours after the ceasefire began and will only gradually withdraw.

He said the pace of the withdrawal and the scheduled return of Lebanese civilians to their homes would depend on whether the deal is implemented and enforced by all sides. The official spoke on condition of anonymity because he wasn't authorized to discuss the deal and its implementation with the media.

The Lebanese military asked displaced returning to southern Lebanon to avoid frontline villages and towns near the border where Israeli troops are still present until they withdraw.

Residents will return to vast destruction wrought by the Israeli military during its campaign, which flattened villages where the military said it found vast weapons caches and infrastructure it says was meant for Hezbollah to launch an Oct. 7-style attack on northern Israel.

More than 3,760 people have been killed by Israeli fire in Lebanon the past 13 months, many of them civilians, according to Lebanese health officials.

Hezbollah emerges from the war battered and bloodied, with the reputation it built by fighting Israel to a stalemate in the 2006 war tarnished. Yet its fighters still managed to put up heavy resistance on the ground, slowing Israel’s advance while continuing to fire scores of rockets, missiles and drones across the border each day.

In Israel, the mood was far more subdued, with displaced Israelis concerned that the deal did not go far enough to rein in Hezbollah and that it did not address Gaza and the hostages still held there.

“I think it is still not safe to return to our homes because Hezbollah is still close to us,” said Eliyahu Maman, an Israeli displaced from the northern Israeli city of Kiryat Shmona, which is not far from the border with Lebanon and was hit hard by the months of fighting.

On Wednesday morning, Kiryat Shmona remained quiet on a cold, rainy day. A handful of people milled about, inspecting damage from earlier rocket attacks, including to the roof of a bus. The town’s shopping mall, which had been hit before, appeared to have new damage, and a rocket was seen stuck in the ground next to an apartment building.

The fighting killed more than 70 people in Israel, more than half civilians, as well as dozens of Israeli soldiers fighting in southern Lebanon.

A significant return of the displaced to their communities, many of which have suffered extensive damage from rocket fire, could take months.

But Israel can claim major victories in the war, including the killing of Hezbollah’s top leader Hassan Nasrallah and most of its senior commanders, as well as the destruction of extensive militant infrastructure. A complex attack involving exploding pagers and walkie-talkies, widely attributed to Israel, appeared to show a remarkable degree of penetration of the secretive militant group.

Chehayeb reported from Beirut. Goldenberg reported from Tel Aviv, Israel. Associated Press journalists Alon Bernstein in Haifa, Israel, Leo Correa in Kiryat Shmona, Israel, and Josef Federman in Jerusalem contributed to this report.

Find more of AP’s war coverage at https://apnews.com/hub/israel-hamas-war

Rescuers use an excavator as they search for victims at the site of an Israeli airstrike that hit a building in Beirut, Tuesday, Nov. 26, 2024. (AP Photo/Hassan Ammar)

People take shelter in a metro station as a siren sounds a warning of incoming rockets from Lebanon in Haifa, Tuesday, Nov. 26, 2024. (AP Photo/Francisco Seco)

People celebrate after a ceasefire between Israel and Hezbollah went into effect in Sidon, Lebanon, Wednesday, Nov. 27, 2024. (AP Photo/Mohammed Zaatari)

People hug each other upon their arrival at their neighborhood as they celebrate a ceasefire between Hezbollah and Israel, which began early morning, in Tyre, south Lebanon, Wednesday, Nov. 27, 2024. (AP Photo/Hussein Malla)

People in a car return back to their villages with their belongings after a ceasefire between Hezbollah and Israel began early morning, as they pass in front of a destroyed building that was hit in an Israeli airstrike, in Tyre, south Lebanon, Wednesday, Nov. 27, 2024. (AP Photo/Hussein Malla)

People sit in traffic as they return to their villages after a ceasefire between Israel and Hezbollah went into effect in Ghazieh, Lebanon, Wednesday, Nov. 27, 2024. (AP Photo/Mohammed Zaatari)

A woman carries a picture of slain Hezbollah leader Hassan Nasrallah as she returns to Dahiyeh, in Beirut, Lebanon, following a ceasefire between Israel and Hezbollah, Wednesday, Nov. 27, 2024. (AP Photo/Bilal Hussein)

Displaced families carry mattresses as they prepare to return to their villages after a ceasefire between Israel and Hezbollah went into effect in Sidon, Lebanon, Wednesday, Nov. 27, 2024. (AP Photo/Mohammed Zaatari)