Vupanorsen falls short despite HDL-C reduction in TRANSLATE-TIMI 70

The antisense oligonucleotide inhibitor ANGTYL3 vupanorsen provided a significant reduction in non-high-density lipoprotein cholesterol (HDL-C) in adults with hyperlipidemia at 24 weeks.

Late-breaking data from the TRANSLATE-TIMI 70 trial presented at the American College of Cardiology (ACC) Scientific Sessions in Washington, D.C., this weekend showed that the experimental monthly injection therapy could provide clinicians a new way to lower patient lipids.

However, investigators also found that liver-targeting vupanorsen was associated with significant elevations in patients’ liver enzymes, a risk that investigators believe may outweigh the benefit of lipid-lowering ability seen with the drug.

In an interview with HCP Live at ACC 2022, study author Brian A. Bergmark, MD, associate physician in interventional cardiology at Brigham and Women’s Hospital, described the “fairly modest” impact of vupanorsen on other markers of LDL-C hyperlipidemia and apolipoprotein B (ApoB). Coupled with unanticipated safety results, future evaluation of the once-promising agent may have to come from a different indicated use.

“Personally, I think these safety results are concerning enough that there’s little chance of a future for this drug at these higher doses,” Bergmark said. “For example, at the highest dose we studied, there was a 76% increase in liver fat and fairly frequent elevations in liver enzymes.”

Bergmark explained that the TRANSLATE-TIMI 70 data is proof of the benefits of clinical trials: “It’s proof that the science works,” he said. Nonetheless, he noted the diversity of ongoing clinical research on lipid-targeting drugs for the prevention of cardiovascular events.

“This is just one of many, and as it expands, I think we’re going to start to see a lot of different ways to understand how to better address lipid risk for patients,” did he declare.

Bergmark also highlighted some promising lipid-lowering agents, as well as the status of lipoprotein A (Lp[a])-targeting drugs and how it can improve the field of cardiovascular prevention.

“We’re going to learn a lot more about the specific importance of different lipoproteins for different people, and I think over time we’ll develop a more personalized and nuanced approach to that,” he said.

The study, “Effect of Vupanorsen on Non-High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients with Elevated Cholesterol – TRANSLATE-TIMI 70,” was presented at ACC 2022.

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