乌鸦传媒

CHICAGO – The incidence of cardiovascular (CV) events did not budge for patients with type 2 diabetes (T2D) who received pemafibrate versus placebo, although the study agent did cut triglycerides and various cholesterol outcomes, according to the PROMINENT trial.

Still, the benefit wasn't enough to save pemafibrate in this setting: In April 2022, that "it would not continue the phase III PROMINENT study, "[b]ased on the review of a planned interim analysis [indicating that] the primary endpoint was unlikely to be met. Notable safety concerns were not raised...Full data from the trial will be presented as soon as possible at a future conference."

Aruna Das Pradhan, MD, of Brigham & Women's Hospital/Harvard Medical School in Boston, reported at the American Heart Association (AHA) annual meeting that in T2D patients with mild-to-moderate hypertriglyceridemia and low HDL and LDL cholesterol levels, there were 573 primary endpoint events with pemafibrate and 560 events with placebo (HR 1.03, 95% CI 0.91-1.15).

"The primary efficacy endpoint was a composite of nonfatal myocardial infarction [MI], ischemic stroke, coronary revascularization, or death from cardiovascular causes," Das Pradhan and colleagues wrote in a simultaneously published (NEJM) article.

However, PROMINENT did yield some good news for lipid levels at 4 months, with better results with pemafibrate versus placebo for:

• Triglycerides: -26.2%
• very LDL cholesterol: -25.8%
• Remnant cholesterol defined as "cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling:" -25.6%
• Apolipoprotein C-III: -27.6%
• Apolipoprotein B: 4.8%

For adverse events, there were no significant differences between the two groups, although pemafibrate was linked with a higher incidence of adverse renal events and venous thromboembolism, but a lower incidence of nonalcoholic fatty liver disease (NAFLD).

Pemafibrate is a selective peroxisome proliferator-activated receptor α modulator that has been shown to cut triglyceride levels and boost other lipid levels. The agent is marketed as Parmodia in Japan.

At an AHA press conference, Das Pradhan said the findings of limited benefit with pemafibrate underscored that the best proven way to lower triglycerides and prevent CV events is diet and exercise, particularly low-carbohydrate, high-protein diets."

In an NEJM , Salim Virani, MD, PhD, of the Baylor College of Medicine in Houston, stated that "fibrates should not be used to reduce the risk of atherosclerotic cardiovascular disease among statin-treated patients," based on PROMINENT results. However, the fibrates "may still have a role to play in decreasing the risk of pancreatitis associated with severe hypertriglyceridemia and perhaps [NAFLD]," he said. Koma said in the press release that it will continue to look at the pemafibrate as a potential treatment for NAFLD and and nonalcoholic steatohepatitis ().

Virani added that "triglyceride lowering without decreases in the apolipoprotein B level will probably not suffice if therapies...are to produce meaningful decreases in the risk of atherosclerotic cardiovascular disease."

enrolled 10,497 individuals with T2D, about 67% of whom had previous CV disease. They had a median baseline fasting triglyceride level of 271 mg per deciliter, an HDL cholesterol level 33 mg/dl, and an LDL cholesterol level 78 mg/dl. Median age in both group was 43, over a quarter were female, and 85% were white, wih a little less than half based in Europe. Median BMI was 32. Patients were eligible if they were on statins, if they were they were untreated, or if they were receiving other cholesterol-lowering medications, but 95% were on statins. Median follow-up was 3.4 years.

Looking specifically at the primary endpoints, Das Pradhan's group reported:

• MI: 205 patients (1.25/100 persons/year) with pemafibrate and 178 patients (1.08/100 persons/year) with placebo
• Non-fatal ischemic stroke: 95 (0.58) and 104 patients (0.63)
• Coronary revascularization: 334 (2.08) and 344 (2.18)
• Death from CV causes: 133 (0.78)and 133 (0.78)
• Death from any cause: 414 (2.44) and 399 patients (2.34)

Das Pradhan said that research in developing other drugs to reduce triglycerides and cardiac events continues in several areas, while Virani noted that the and trials offered similar results to PROMINENT in terms of triglyceride lowering.