US FDA approves world's first oral cholesterol-lowering pill: What it means for patients

Patients with difficult-to-control high cholesterol may soon have an oral alternative to injectable cholesterol-lowering drugs after the US Food and Drug Administration (FDA) approved Lipfendra (enlicitide), the world's first oral PCSK9 inhibitor. The once-daily pill is designed to significantly reduce low-density lipoprotein (LDL), or "bad" cholesterol.

The drug has been approved for adults with high cholesterol, including those with heterozygous familial hypercholesterolaemia (HeFH), an inherited condition that causes very high cholesterol levels. It is meant to be used alongside diet, exercise and existing cholesterol-lowering medicines. Until now, PCSK9 inhibitors have only been available as injections administered every two or four weeks.

Not available in India yet

The newly approved drug is not expected to reach the Indian market immediately.


"Even if a medicine is approved abroad, it cannot be marketed in India automatically. Besides patent-related restrictions, it must obtain approval from CDSCO after following the prescribed regulatory process, which may include clinical trials as required under Indian regulations," said Dr Subhash Mandal, national general secretary, Indian Pharmaceutical Association (IPA).

"In exceptional cases, patients may seek permission through a separate CDSCO mechanism to import limited quantities for personal treatment. However, medicines cannot simply be brought into the country by friends or relatives," he said.

Why the approval matters

The FDA's approval is significant because many patients at high risk of heart disease continue to have elevated LDL cholesterol despite taking standard oral medicines such as statins.

Indian cardiology guidelines recommend reducing LDL cholesterol to below 70 mg/dL for high-risk patients and below 55 mg/dL for those at very high cardiovascular risk. However, many patients fail to achieve these targets despite multiple therapies.

With cardiovascular disease remaining the leading cause of death in India, doctors say improving LDL control is essential to reducing the risk of heart attacks and strokes.

Clinical trials involving 3,207 adults showed that the once-daily tablet reduced LDL cholesterol by 56-59% over 24 weeks in patients already taking maximally tolerated statins. The results are comparable to those achieved by injectable PCSK9 inhibitors, offering another treatment option for patients whose cholesterol remains uncontrolled despite existing medications.

However, cardiologists emphasised that the new drug is unlikely to replace statins or become a first-line therapy.

"PCSK9 inhibitors have so far been available only as injections every two or four weeks. The new oral therapy lowers LDL, or 'bad' cholesterol, by about 50-60%, making it a promising option for patients who prefer to avoid injections," said Dr Ambuj Roy, Professor of Cardiology at AIIMS Delhi.

High LDL cholesterol is a major risk factor for heart disease and stroke because it leads to the build-up of fatty plaques inside arteries, increasing the likelihood of heart attacks and strokes.