New Delhi: A new daily pill could potentially lower high cholesterol in a way that was previously possible only with injections. The US Food and Drug Administration (FDA) on Thursday approved Lipfendra (enlicitide), developed by American pharmaceutical company Merck, for adults with high “bad” cholesterol.
It is the world’s first oral PCSK9 inhibitor, a new type of cholesterol-lowering medicine that, until now, was available only as an injection. PCSK9 inhibitors are a class of medicines that lower “bad” (Low-Density Lipoprotein or LDL) cholesterol by helping the liver remove more of it from the blood.
LDL cholesterol is called “bad” cholesterol because excess LDL sticks to the walls of arteries, gradually forming fatty plaques that reduce blood flow. If one of these plaques ruptures, it can trigger a heart attack or stroke.
The once-daily pill has been approved for adults with high LDL cholesterol, including those with an inherited condition called heterozygous familial hypercholesterolemia (HeFH), which causes very high cholesterol from birth.
“This is an important advance because it offers another option for patients whose cholesterol remains high despite taking the best available dose of statins,” Dr Chetan Kumar HB, senior consultant in cardiology at Fortis Hospital, Bengaluru, told ThePrint.
However, he said, statins will continue to remain the first choice for treating high cholesterol because decades of research have shown they reduce the risk of heart attacks and strokes. Statins work by reducing the amount of cholesterol produced by the liver and have been the standard treatment for high cholesterol for more than three decades.
High LDL usually does not cause any symptoms, so many people discover they have high cholesterol only through a blood test.
According to the World Health Organization (WHO), cardiovascular disease caused nearly 19.8 million deaths worldwide in 2022, making it the leading cause of death globally.
India also faces a growing burden. The Indian Council of Medical Research -INDIAB study estimates that 213 million Indians have high cholesterol, including 185 million with elevated LDL cholesterol.
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How is this pill different
PCSK9 inhibitors are not new medicines. Doctors have been prescribing injectable PCSK9 medicines such as Repatha, Praluent and, more recently, Leqvio for people whose cholesterol remains high despite taking statins.
What makes Lipfendra different is that it comes as a pill instead of an injection.
It works by blocking the PCSK9 protein. Typically, the PCSK9 protein breaks down the liver cells that clean out bad cholesterol. If PCSK9 is blocked, those liver cells stay alive and healthy. This helps the liver pull much more bad cholesterol out of the blood.
For many patients, the biggest advantage could simply be that it is easier to take.
“People with diabetes, obesity or thyroid disorders often remain at high risk of heart disease even after making lifestyle changes and taking statins. A pill may be more convenient for some patients than injections,” said Dr Nishchitha K, consultant endocrinologist at Fortis Network’s Gleneagles Hospital in Bengaluru.
She emphasised that the medicine is not meant for everyone with high cholesterol.
“The drug should only be prescribed following a thorough medical evaluation. It should also be associated with a healthy diet, regular physical activity, weight control, and good control of conditions such as diabetes and high blood pressure,” she added.
What the trials showed
The FDA approval is based on two Phase III clinical trials involving 3,207 adults already taking the highest dose of statins they could tolerate.
In one study involving people with heart disease or a high risk of developing it, Lipfendra reduced LDL cholesterol by 56 percent after 24 weeks compared with those who took placebo. In another study, involving patients with inherited high cholesterol, LDL cholesterol fell by 59 percent.
The drug also lowered other blood markers linked to cardiovascular disease.
The most commonly reported side effects included diarrhoea and dizziness, though most participants tolerated the medicine well. However, Merck is still conducting another large trial to determine whether lowering cholesterol with Lipfendra actually translates into fewer heart attacks and strokes.
What could it mean for patients on statins
Doctors say that the pill is expected to be most useful for people at very high risk of heart disease, including those with diabetes who have already had a heart attack or stroke, people with chronic kidney disease, and those with an inherited condition called familial hypercholesterolemia.
According to Dr Rajiv Kovil, diabetologist and obesity specialist at Zandra Healthcare in Mumbai, the pill could also overcome one of the biggest barriers to advanced cholesterol treatment in India — the need for injections.
“Many patients are reluctant to start injectable medicines because of needle anxiety or the inconvenience of taking injections. A daily pill fits more naturally into the routine of people who are already taking medicines for diabetes or blood pressure,” he said.
However, Dr Kovil cautioned that a tablet does not automatically mean better treatment adherence. Many people with diabetes already take several medicines every day, so adding another pill could increase the treatment burden.
He also said the drug’s impact in India will depend largely on its price. “A scientifically impressive medicine will have limited public health impact if it is too expensive for most patients,” he said.
(Edited by Ajeet Tiwari)
Also Read: Why new guidelines in US recommend screening for ‘bad cholesterol’ as early as ages 9-11