Vupanorsen reduces non-HDL-C levels in adults with hyperlipidaemia already on statins

Vupanorsen significantly reduces non–high-density lipoprotein cholesterol (non-HDL-C) levels in adults with hyperlipidaemia, according to the TRANSLATE-TIMI 70* trial presented at ACC 2022.

The researchers conducted a placebo-controlled, double-blind, dose-ranging study involving 286 adults (median age 64.0 years, 44.0 percent female) on statin treatment who had baseline median non-HDL-C level of ≥132 mg/dL and triglyceride level of 216 mg/dL from 55 sites in three countries (US, Canada, and Poland). Participants were randomized to receive one of the seven subcutaneous vupanorsen dosing regimens for every 4 weeks (Q4W arm: 80 mg [n=23], 120 mg [n=23], or 160 mg [n=45]) or every 2 weeks (Q2W arm: 60 mg [n=23], 80 mg [n=42], 120 mg [n=46], or 160 mg [n=35]) or placebo (n=44). [ACC 2022, abstract 405-08]

Patients treated with vupanorsen achieved a significantly reduced non-HDL-C at 24 weeks in both the Q4W and the Q2W arms (placebo-adjusted percentage change, ranging from -22.4 to -26.6 percent and from -22.0 to 27.7 percent, respectively; p<0.001 for all doses).

With regard to additional lipid parameters, all vupanorsen dosing arms also showed a decreased ANGPTL3** levels in a dose-dependent manner at week 24 in both the Q4W (placebo-adjusted percentage, -69.9 percent to -80.4 percent) and the Q2W arms (placebo-adjusted percentage, -79.6 percent to -95.2 percent).

A dose-dependent reduction in triglyceride levels was also observed in all doses of vupanorsen at week 24 in both arms (placebo-adjusted percentage change, -41.3 percent to -45.9 percent [for Q4W arm] and -43.8 percent to -56.8 [for Q2W arm]).

The treatment effect of vupanorsen resulted in modest reductions of up to -14.5 percent for low-density lipoprotein cholesterol (LDL-C)  in the Q4W 160 mg arm and up to -16.0 percent for apolipoprotein B (ApoB) in the Q2W 80 mg arm, but with no clear dose-response relationship, the researchers noted.

Overall, adverse events of any grade occurred in approximately 70.0 percent of the participants, but there were no confirmed cases of worsening renal function or thrombocytopenia (platelet count of <100,000 per mm³), said lead author Dr Brian Bergmark from the Brigham and Women’s Hospital in Boston, Massachusetts, US.

Injection-site reactions and ALT/AST*** elevations were most common with the vupanorsen 160 mg dosing regimen for both Q4W (16.0 percent and 9.0 percent, respectively) and Q2W arms (33.0 percent and 39.0 percent, respectively).

“[This study showed that] in statin-treated adults with hyperlipidaemia, vupanorsen significantly reduced non-HDL-C and … additional lipid parameters, [such as ANGPTL3, triglycerides, LDL-C, and ApoB], at certain doses,” Bergmark said.

“Many of these findings were not anticipated by genetic, preclinical, and earlier clinical data, and [therefore,] ultimately, this trial emphasizes the importance of rigorous evaluation of new lipid-lowering therapies and may provide mechanistic insight as additional metabolic targets are studied going forward,” he added.

*TRANSLATE-TIMI 70: A dose-ranging study with vupanorsen

**ANGPTL3: Angiopoietin-like protein 3