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Scientists are testing an experimental treatment to help lower triglycerides. Inuk Studio/Stocksy
  • Triglycerides are a form of blood fat.
  • High levels of triglycerides are linked to increased heart disease risk.
  • Two recent studies find that an injectable experimental drug significantly reduces levels.
  • The drug, called olezarsen, may be particularly useful for people with a rare condition that causes raised triglyceride levels.

Two recent studies, published in The New England Journal of Medicine, investigated a new drug called olezarsen, which is designed to reduce levels of “bad” fat in the blood called triglycerides.

Both studies found that olezarsen significantly lowered triglyceride levels.

Olezarsen, produced by Ionis Pharmaceuticals, also reduced the levels of other blood fats associated with disease risk.

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

Around 95% of the fats we eat are triglycerides, an essential source of energy. After eating, triglycerides eventually reach your bloodstream.

Once there, they travel to your muscles to be used as energy or to liver and fat cells for storage.

While triglycerides are vital for health, high levels are associated with an increased risk of heart disease and stroke.

When triglycerides are at particularly high levels, doctors call it hypertriglyceridemia. In severe cases, this can lead to acute pancreatitis — an acute inflammation of the pancreas, which, in severe cases, can lead to death.

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

An estimated 1 in 4 people in the United States have high triglyceride levels.

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

Certain lifestyle interventions, such as a healthy diet, regular physical activity, and stopping smoking, can also help reduce triglyceride levels.

However, Kenneth Feingold, MD, Emeritus professor of medicine at the University of California San Francisco who was not involved in the study, told Medical News Today that “lifestyle changes are extremely difficult to achieve” for people with familial chylomicronemia syndrome. They need to follow an extremely low fat diet.”

“Therefore, getting satisfactory reductions in triglyceride levels is very difficult with lifestyle.” Some people will benefit, but “in other patients, the elevated triglyceride levels are primarily due to genetic factors, and lifestyle changes have only a moderate effect,” he said.

The first study recruited 154 participants with either severe hypertriglyceridemia or moderate hypertriglyceridemia plus elevated cardiovascular risk.

They received a monthly olezarsen injection or a placebo. Those receiving olezarsen were further split into two groups: The first group received a 50-milligram (mg) dose and the second group an 80-mg dose.

Compared with placebo, those taking olezarsen reduced their triglyceride levels by 49.3% (50 g group) and 53.1% (80 mg group).

They also saw significant reductions in other blood fats linked to cardiovascular risk — namely, APOC3, apolipoprotein B, and non-HDL cholesterol.

For the second study, the scientists recruited 66 people with familial chylomicronemia syndrome. Split into three groups, the participants received a placebo, 50 mg of olezarsen every 4 weeks, or 80 mg of olezarsen every 4 weeks. The study ran for 53 weeks.

At 6 months, the scientists found that the 80-mg dose significantly reduced triglyceride levels, but the 50-mg dose did not.

Importantly, there was also a reduction in acute pancreatitis.

MNT reached out to Ionis Pharmaceuticals. They explained that ”Only one patient in the 80 mg group […] experienced an episode of acute pancreatitis, compared with 11 in the placebo group. This important finding supports the potential for olezarsen to be the standard of care for patients with [familial chylomicronemia syndrome].”

MNT contacted a number of experts, none of whom were involved in the study, but all had similar thoughts on the research.

For instance, Cheng-Han Chen, MD, board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, told MNT that olezarsen “appears to be much more effective than current therapies in lowering triglyceride levels in patients with severely elevated levels.”

Gerald Watts, Winthrop professor of internal medicine at the University of Western Australia, wrote an editorial on the two new studies.

MNT asked whether the drug was likely to be approved. Watts said he expects that olezarsen will soon be approved for familial chylomicronemia syndrome, but we need more research for people with moderate-to-high triglycerides,.

While olezarsen may be useful for people with elevated triglycerides, most experts believe its primary use will be in people with familial chylomicronemia syndrome.

“For these people,” Feingold explained, “there are currently no drugs in the U.S. that are effective in lowering triglyceride levels and reducing the risk of pancreatitis. There is a major need for a drug to treat this rare disorder that causes considerable morbidity.”

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

MNT contacted Ioanna Gouni-Berthold, MD, a professor of internal medicine and head of the Lipid Research Clinic at the University of Cologne, Germany. Similarly, she believes that olezarsen “is definitely going to be a great addition to the treatment of familial chylomicronemia syndrome.”

While these results are exciting, particularly for people with familial chylomicronemia syndrome, the overall benefits for individuals with moderately high triglycerides are less clear.

“For patients with moderate hypertriglyceridemia, the decrease in triglycerides was impressive and better than other drugs. Of note, olezarsen not only lowered triglyceride levels 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 on statin therapy have been unable to demonstrate that lowering triglyceride levels reduces the risk of cardiovascular disease.”

So, before olezarsen is recommended for these people, Feingold said “we need studies that demonstrate that treatment with this drug decreases the development of atherosclerosis and the risk of cardiovascular events.”

Cheng echoed this sentiment: “Longer-term studies examining safety and efficacy will be necessary before this therapy becomes mainstream.”

Feingold also called for longer and larger studies to ensure the drugs are safe. He explained that some evidence suggests that olezarsen “might affect platelets in certain patients.”

Watts was on the same page. In his editorial, he writes, “Because the trial participants were mainly adults and white, and the trials were of relatively short duration, additional, longer trials that include persons of non-European ancestries are needed.”

Overall, though, he believes that the drug will be useful. “[C]urrent therapies for severely elevated levels of triglycerides are ineffective, with a continuing risk of life threatening acute pancreatitis, a gap that will probably be closed by olezarsen,” said Watts.