Experimental drug lowers blood levels of 'bad' fats

Two recent studies published in the New England Journal of Medicine examined a new drug called olesarsen, which is designed to lower levels of "bad" fats in the blood called triglycerides.

Both studies showed that olesarsen significantly reduced triglycerides.

Olesarsen, manufactured by Ionis Pharmaceuticals, also lowers levels of other fats in the blood associated with disease risk.

The drug may soon be approved for people with a rare condition called familial chylomicronemia syndrome, who are likely to benefit most from the drug.

Are all blood fats harmful?

About 95% of the fats we eat are triglycerides, an important source of energy. After eating, triglycerides eventually enter the bloodstream.

Once there, they travel to the muscles where they are used as energy, or to the liver and fat cells for storage.

Although triglycerides are vital to health, high levels are associated with an increased risk of cardiovascular disease and stroke.

When triglyceride levels are particularly high, doctors call it hypertriglyceridemia. In severe cases, this can lead to acute pancreatitis - an acute inflammation of the pancreas that can be fatal in severe cases.

Familial chylomicronemia syndrome is a rare disorder that results in elevated triglyceride levels. People living with this condition have an even higher risk of developing acute pancreatitis.

Reduction of "bad" fats in the bloodstream

It is estimated that one in four people in the United States has high triglyceride levels.

Some of these people respond well to medications such as statins. However, treatments that have a direct effect on triglycerides are limited.

Certain lifestyle changes such as eating a healthy diet, exercising regularly, and quitting smoking can also help lower triglyceride levels.

However, Kenneth Feingold, M.D., professor emeritus of medicine at the University of California, San Francisco, who was not involved in the study, said that people with familial chylomicronemia syndrome "are extremely difficult to achieve lifestyle changes. They need to follow an extremely low-fat diet."

"Therefore, it is very difficult to achieve a satisfactory reduction in triglyceride levels with lifestyle changes." Some people will benefit, but "in other patients, elevated triglycerides are primarily due to genetic factors, and lifestyle changes have only a moderate effect," he said.

The Olezarsen study and cardiovascular disease risk

The first study enrolled 154 participants with either severe hypertriglyceridemia or moderate hypertriglyceridemia plus increased cardiovascular risk.

They received monthly injections of olesarsen or placebo. Patients who received olesarsen were divided into two groups: the first group received a 50 milligram (mg) dose and the second group received an 80 mg dose.

Compared to placebo, those who took olesarsen had a 49.3% (50g group) and 53.1% (80mg group) reduction in triglyceride levels.

They also observed significant reductions in other blood fats associated with cardiovascular risk, namely APOC3, apolipoprotein B, and non-HDL cholesterol.

Olesarsen's second study and acute pancreatitis

For the second study, the researchers recruited 66 people with familial chylomicronemia syndrome. Divided into three groups, the participants received placebo, 50 mg of olesarsen every 4 weeks, or 80 mg of olesarsen every 4 weeks. The study lasted 53 weeks.

After 6 months, the researchers found that an 80 mg dose significantly reduced triglyceride levels, while a 50 mg dose did not.

Importantly, there was also a decrease in the incidence of acute pancreatitis.

Researchers from Ionis Pharmaceuticals explained that "only one patient in the group taking 80 mg had an episode of acute pancreatitis compared to 11 in the group taking placebo. This important finding supports the possibility of olesarsen becoming the standard of care for patients with [familial chylomicronemia syndrome]."

Significant benefits to the heart and pancreas

Cheng-Han Chen, M.D., a board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, California, said that olesarsen "appears to be much more effective than existing treatments in lowering triglyceride levels. Levels in patients with severely elevated levels."

Gerald Watts, Winthrop Professor of Internal Medicine at the University of Western Australia, wrote an editorial about two new studies.

Will the drug be approved? Watts said he expects olesarsen to be approved soon for the treatment of familial chylomicronemia syndrome, but we need more studies for people with moderate to high triglyceride levels.

Although olesarsen may be useful for people with elevated triglyceride levels, most experts believe it will primarily be used by people with familial chylomicronemia syndrome.

"For these individuals," Feingold explained, "there are currently no drugs in the U.S. That are effective at lowering triglyceride levels and reducing the risk of pancreatitis. There is an urgent need for a drug to treat this rare disease that causes significant morbidity."

He called the drug "a significant advance in the treatment of patients with this disorder."

Can this drug be used to treat cardiovascular disease?

While these results are impressive, especially for people with familial chylomicronemia syndrome, the overall benefits for people with moderately high triglyceride levels are less clear.

"In patients with moderate hypertriglyceridemia, the triglyceride reduction was impressive and better than other drugs. Of note, olesarsen not only lowered triglycerides, but also lowered non-HDL cholesterol and apolipoprotein B levels," Feingold said.

However, he added a caveat: "Previous studies with other triglyceride-lowering drugs in patients receiving statin therapy have failed to demonstrate that lowering triglycerides reduces the risk of cardiovascular disease."

So before recommending olesarsen to these people, Feingold said, "we need studies that demonstrate that treatment with this drug reduces the development of atherosclerosis and the risk of cardiovascular events."

Cheng supported this view, "Long-term studies examining safety and efficacy will be needed before this therapy becomes generally accepted."

Feingold also called for longer and larger studies to see if the drugs are safe. He explained that some evidence suggests that olesarsen "may affect platelets in some patients."

The study is published in New England Journal of Medicine.