UAE clears first oral PCSK9 cholesterol treatment

The UAE has approved Lipfendra, a once-daily pill designed to sharply reduce harmful cholesterol, becoming the second country after the United States to authorise the first oral treatment targeting the PCSK9 protein.

The Emirates Drug Establishment approved the medicine for adults with elevated low-density lipoprotein cholesterol, or LDL-C, including those with heterozygous familial hypercholesterolaemia, an inherited disorder that causes dangerously high cholesterol levels. The treatment must be prescribed by a healthcare professional and used alongside diet and exercise.

Lipfendra contains enlicitide, a medicine developed by US pharmaceutical company Merck, which operates as MSD outside the United States and Canada. The 20mg tablet offers a non-injectable alternative within a drug class that has produced substantial cholesterol reductions but has previously been available only through injections.

The UAE authorisation was announced on August 1, about two weeks after US regulators approved the medicine on July 16. The rapid clearance highlights the country’s strategy of accelerating access to pharmaceutical innovations after evaluations by established international regulators.

Clinical evidence supporting the approvals came from two Phase III studies involving 3,207 adults who were already receiving the maximum statin dose they could tolerate. Participants included people with established atherosclerotic cardiovascular disease, those considered at high risk and patients with inherited high cholesterol.

Lipfendra reduced LDL-C by 56 per cent compared with a placebo after 24 weeks among adults with cardiovascular disease or a heightened risk of developing it. Participants in that trial had an average LDL-C level of 96 milligrams per decilitre when the study began.

Among patients with heterozygous familial hypercholesterolaemia, whose average starting level was 119 milligrams per decilitre, the medicine produced a placebo-adjusted reduction of 59 per cent over the same period. Lower levels of other artery-damaging particles, including non-HDL cholesterol and apolipoprotein B, were also recorded.

PCSK9 is a protein that contributes to the destruction of receptors used by the liver to remove LDL cholesterol from the bloodstream. By blocking the protein, enlicitide preserves more of those receptors, allowing the liver to clear greater quantities of cholesterol.

Injectable medicines using the same mechanism have been available for more than a decade. They include products from Amgen, Sanofi and Regeneron Pharmaceuticals. Their use has remained limited in some markets because of cost, insurance restrictions, injection requirements and prescribing practices.

An oral version could widen access, particularly for people who are reluctant to use injections or require additional treatment beyond statins. Statins remain the standard first-line medicines because they are widely studied, inexpensive and proven to reduce heart attacks and strokes.

Lipfendra is not intended to replace lifestyle changes or eliminate the need for established therapies. Its role will depend on each patient’s cholesterol level, cardiovascular risk, medical history and response to other drugs.

The medicine is taken once a day. Prescribing information advises patients to take it on an empty stomach, at least two hours after eating and at least 30 minutes before the next meal. Other oral medicines should generally be taken four hours after Lipfendra because food and accompanying drugs may reduce its absorption.

The safety profile was broadly similar to placebo among patients with cardiovascular disease or elevated risk. Diarrhoea and dizziness were reported more frequently among participants with inherited high cholesterol. Treatment discontinuation because of adverse reactions was comparable between the medicine and placebo groups.

While reductions in LDL cholesterol are strongly linked with lower cardiovascular risk, Lipfendra has not yet been shown directly to prevent heart attacks, strokes or cardiovascular deaths. A large outcomes trial is under way to determine whether its cholesterol-lowering effect translates into fewer major cardiovascular events.