Promotion of a New Drug in Managing High Triglyceride Levels

A significant international clinical trial led by Dr. Hofit Cohen from Sheba Medical Center in Israel has revealed promising results for a new medication that can lower triglyceride levels by over 50%. This treatment also notably reduces the risk of potentially fatal pancreatitis. The study, which involved nine medical centers in Israel, was recently published in the New England Journal of Medicine and presented at the American Heart Association’s annual conference in New Orleans.

Dr. Cohen, who directs the Lipid Disorders Diagnosis and Treatment Service at Sheba’s Strasburger Lipid Center, shared a compelling case of a 50-year-old real estate appraiser. This patient had endured six episodes of pancreatitis in recent years and, despite adhering to strict dietary guidelines and maximum medication, he faced regular hospital visits, including times in intensive care. After undergoing treatment in the study, his triglyceride levels normalized, and he hasn’t required emergency care since.

“This is a genuine breakthrough,” Cohen remarked. “Previously, there was no effective solution for patients grappling with very high triglyceride levels and recurrent pancreatitis. The study indicated a significant reduction in triglycerides, along with a dramatic decrease in pancreatitis risk. This is a treatment that can greatly change patients’ lives.”

Understanding Triglycerides and Their Risks

So, what exactly are triglycerides? Well, they’re a type of fat found in the blood, composed of three fatty acids attached to glycerol. After we eat, our intestines produce triglycerides and circulate them through the bloodstream using chylomicrons. The liver similarly creates particles known as VLDL, which carry triglycerides for energy or storage in body fat.

Normal triglyceride levels are generally considered to be below 150 mg/dL. When levels range from 150 to 499 mg/dL, they are deemed elevated, rising to significantly high between 500 and 999, and anything above 1,000 mg/dL is categorized as extremely high, posing risks for both pancreatitis and cardiovascular disease.

Elevated triglycerides heighten the risk for conditions like atherosclerosis, heart attacks, strokes, and peripheral vascular disease. Very high levels can sharply increase the risk for acute pancreatitis, which can sometimes be life-threatening, necessitating intensive care and possibly leading to lasting damage.

Dr. Cohen explained that elevated triglycerides often stem from a mix of genetic and lifestyle factors. Diets high in fats and simple carbohydrates, a sedentary lifestyle, excessive alcohol consumption, uncontrolled diabetes, kidney issues, hypothyroidism, an overabundance of cortisol, and central obesity all contribute significantly to rising levels. Some rare genetic disorders can also hinder the body’s ability to metabolize triglycerides, resulting in dangerously high levels at a young age.

Typically, treatment starts with lifestyle modifications, such as a balanced diet, reducing carbohydrates, avoiding alcohol, exercising regularly, and managing diabetes effectively. Many patients also take statins to lower the risk of heart disease. For triglyceride levels that exceed 500 mg/dL, doctors usually prescribe fibrates or high-dose omega-3 fatty acids, which can lower levels by 30% to 50%.

However, for some individuals—especially those with extreme levels—these strategies don’t suffice, and they continue to suffer from recurrent pancreatitis despite following treatment plans. In severe cases, a procedure called plasmapheresis, which mechanically removes triglycerides from the blood, becomes necessary, sometimes performed weekly or biweekly.

Recently, advanced RNA-based therapies have changed the landscape for treating severe hypertriglyceridemia. These approaches focus on specific proteins involved in triglyceride metabolism. A crucial one, apoC-III, normally inhibits triglyceride breakdown. Suppressing its production helps significantly enhance the body’s ability to eliminate fats.

Volanesorsen was the first drug in this new class, and it’s been approved in Europe. Olezarsen, a newer drug, acts in a similar way but targets the liver and is considered safer. The FDA approved it in 2024 for a rare genetic condition called familial chylomicronemia syndrome (FCS), and it should be arriving in Israel soon.

The CORE trials sought to determine whether Olezarsen could assist adults with severe hypertriglyceridemia who hadn’t been able to achieve safe levels despite lifestyle changes and conventional therapies.

These extensive, double-blind, placebo-controlled trials included 1,061 participants across 23 countries and approximately 140 medical centers, including nine in Israel. Participants received monthly injections of either Olezarsen or a placebo for a year while researchers monitored changes in triglyceride levels and pancreatitis occurrences.

The results were impressive. Average triglyceride levels dropped from around 800 mg/dL to reductions between 50% and 70%, based on dosage. A remarkable 85% of patients achieved triglyceride levels below 500 mg/dL, and the rate of pancreatitis plummeted by over 80%.

Overall, the drug appeared safe, with similar side effects and treatment discontinuation rates compared to the placebo. Nonetheless, researchers identified some findings that will need monitoring: mild increases in liver enzymes, reduced platelet counts in some individuals (more frequently seen in higher doses), and dose-related increases in liver fat. Long-term follow-up is still in progress.

According to Cohen, patients with extreme triglyceride levels previously had limited options, often resorting to ongoing invasive procedures. Now, Olezarsen provides a transformative alternative that significantly lowers triglycerides, reduces episodes of pancreatitis, and may eliminate the need for plasmapheresis.

“This is a treatment that can change these patients’ lives,” she stated, dubbing it a true breakthrough and “game changer” for severe hypertriglyceridemia management. She emphasized that when combined with healthy lifestyle choices, diabetes management, and existing treatments, the new drug could vastly lower illness and mortality rates among those facing dangerously high triglyceride levels.

Dr. Dov Gavish, chair of the Israel Atherosclerosis Society and senior physician at Shaare Zedek Medical Center, pointed out that these newer medications currently in clinical trials help patients maintain much lower triglyceride levels, decrease pancreatitis incidents, and improve diabetes management. He anticipates more treatments are on the way that could enhance care and prevent serious complications.