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Deepak Bhatt, MD, MPH, discusses results of the phase 2 ENTRIGUE trial and how it informs clinicians on the effects of the human FGF21 analogue in patients with severe hypertriglyceridemia.
Data from the ENTRIGUE trial presented at the American College of Cardiology’s (ACC) 2023 Annual Scientific Session Together With the World Congress of Cardiology suggest use of pegozafermin was associated with statistically significant reductions in triglycerides and atherogenic lipids in patients with severe hypertriglyceridemia
Data from the phase 2 trial of the human FGF21 analogue, results of the study indicate use of pegozafermin was associated with a placebo-corrected median reduction in triglycerides of 42.6% in a population of patients on background lipid-modifying therapies.1
“This new analysis builds on the growing body of evidence demonstrating that treatment with pegozafermin can significantly reduce triglycerides and improve markers of atherogenic risk across a wide variety of patients with SHTG,” said Deepak Bhatt, MD, MPH, Valentin Fuster Professor of Cardiovascular Medicine and director of Mount Sinai Heart.2 “These findings are encouraging given the critical need for new therapeutic options that not only reduce triglyceride levels but also improve broader cardiometabolic risks for patients with SHTG regardless of their lipid-modifying treatment status.”
A 5-arm, double-blind, randomized trial, ENTRIGUE evaluated the effects of 4 different doses of pegozafermin against placebo therapy over an 8-week period. Pegozafermin doses used in the trial included a 9 mg, 18 mg, and 27 mg once weekly or 36 mg every 2 weeks.1
For inclusion in ENTRIGUE, patients needed to have fasting triglycerides in the range of 500-2000 mg/dL. Investigators pointed out participants were allowed to be on background lipid-modifying therapies, such as statins, prescription fish oil, fibrates, or others.1
Designed with the percent change in triglycerides from baseline as the primary outcome of interest, the trial randomized 85 patients, with 18 receiving placebo therapy and 67 receiving doses of pegozafermin. Investigators noted 55% of participants were on some form of background lipid-modifying therapy, including 45% using statins, 14% using prescription fish oil, and 7% using fibrates. Of note, 55% of statin users were using high-intensity statins.1
Upon analysis, results indicated use of pegozafermin was associated with statistically significant reductions in triglycerides, with results pointed to a placebo-corrected median reduction of 42.6% (95% CI, -56.29 to -22.9; P=.001) of patients on background lipid-modifying therapy. Among those treated with pegozafermin, 79.7% reduced their triglyceride levels below 500 mg/dL compared to 29.4% with placebo therapy. Subgroup analyses of those using background lipid-modifying therapy indicated triglyceride levels below 500 mg/dL were achieved by 85.3% of the pegozafermin arm and 45.5% of the placebo arm.1
Further analysis suggested treatment with pegozafermin was associated with significant reductions in both non-HDL-C and ApoB, with a placebo-corrected mean reduction of 17.9% (P=.007) and 11.8% (P=.019), respectively. Investigators noted there was no significant changes in LDL-C among the overall population (LS mean difference, 1.7%; P=.87), but subgroup analysis of people on background lipid-modifying therapy using pegozafermin experienced LDL-C reductions relative to those using placebo therapy (LS mean reduction of 9.0%).1
For more on the results of this trial and the next steps in research, we sat down with Bhatt on the floor at ACC 2023.
Deepak L. Bhatt, MD, MPH, receives consultant fees, honoraria, or research grants from 89Bio, CinCor Pharma, Inc., AstraZeneca, and others. Click here for the full list.