November 15, 2020
3 min read
Rosenson RS, et al. LBS.04: Fish oil, fancy drugs and frustrations in lipid management. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).
The study was funded by Regeneron. Rosenson reports he received grants and/or personal fees from 89Bio, Amgen, Corvidia, CVS Caremark, Kowa, Novartis, Regeneron and The Medicines Company and other fees from MediMergent and UptoDate. Please see the study for all other authors’ relevant financial disclosures. Watson reports she consults for Amarin, Amgen, Boehringer Ingelheim, Eli Lilly and Novartis and serves on the speakers bureau for Boehringer Ingelheim and Eli Lilly.
Evinacumab, a novel fully human monoclonal antibody against angiopoietin-like 3, reduced LDL by more than 50% compared with placebo in patients with refractory hypercholesterolemia, researchers reported.
The patient population included those with refractory hypercholesterolemia despite treatment with statins and other lipid-lowering therapies, Robert S. Rosenson, MD, FACC, FACP, FAHA, FNLA, FACCP, professor of medicine and director of cardiometabolic disorders at Icahn School of Medicine at Mount Sinai, said during a presentation at the virtual American Heart Association Scientific Sessions. He said all patients were taking a PCSK9 inhibitor plus maximally tolerated statin therapy with or without ezetimibe.
For the phase 2 study, 272 patients were randomly assigned to subcutaneous evinacumab (Regeneron) 450 mg per week, 300 mg per week or 300 mg every other week, or placebo; or IV evinacumab 15 mg per kg of body weight every 4 weeks, 5 mg per kg of body weight every 4 weeks, or placebo. All patients had refractory hypercholesterolemia; many had heterozygous familial hypercholesterolemia (FH) and those who did not had atherosclerotic CVD.
The drug targets angiopoietin-like 3 (ANGPTL3) and can reduce LDL independent of the LDL receptor, Rosenson said during the presentation. As Healio previously reported, evinacumab reduced LDL to nearly normal levels in patients with homozygous FH.
In the subcutaneous delivery and IV delivery populations, the evinacumab groups had greater LDL reduction compared with the placebo groups, Rosenson said.
Robert S. Rosenson
In the subcutaneous delivery analysis (mean age, 54 years; 63% women; baseline LDL, 150 mg/dL), the difference in least-squares mean change in LDL from baseline to 16 weeks compared with placebo was –56 percentage points in the evinacumab 450 mg per week group, –52.9 percentage points in the evinacumab 300 mg per week group and –38.5 percentage points in the evinacumab 300 mg every other week group (P < .001 for all), Rosenson said during the presentation.
“There were changes in other atherogenic lipoproteins in subcutaneous administrations,” Rosenson said. “Dose-dependent reductions in apolipoprotein B, non-HDL cholesterol, total cholesterol and triglycerides were observed. There was a non-dose-dependent reduction in lipoprotein(a).”
In the IV delivery analysis (mean age, 55 years; 56% women; baseline LDL, 144.5 mg/dL), the difference in least-squares mean change in LDL from baseline to 16 weeks compared with placebo was –50.5 percentage points in the evinacumab 15 mg per kg of body weight group (P < .001) and –24.2 percentage points in the evinacumab 5 mg per kg of body weight group (P = .0109), he said.
“There were dose-dependent reductions in other atherogenic lipids, including ApoB, non-HDL cholesterol, total cholesterol and triglycerides, and reductions in Lp(a) that were equivalent at 16.5% with both doses.”
Rates of serious adverse events were low, he said.
The results were simultaneously published in The New England Journal of Medicine.
“This phase 2 study demonstrates that evinacumab reduces LDL and other atherogenic lipoproteins in patients with refractory hypercholesterolemia, and is generally well tolerated,” Rosenson said during the presentation. “The addition of evinacumab to standard-of-care lipid-lowering therapy in patients with refractory hypercholesterolemia may potentially facilitate more patients attaining guideline-defined LDL cholesterol goals, and in doing so, has the potential to reduce the risk of cardiovascular disease events and overall mortality.”
Karol E. Watson
The data “give us hope for additional LDL lowering in patients with refractory hypercholesterolemia,” Cardiology Today Editorial Board Member Karol E. Watson, MD, PhD, FACC, professor of medicine/cardiology at David Geffen School of Medicine at UCLA and co-director of the UCLA Program in Preventive Cardiology, said in a discussant presentation. “We know that lowering LDL is the foundation of atherosclerotic cardiovascular disease risk reduction, and statins are the mainstay. We know that the addition of nonstatin therapies may be useful for high-risk patients if the LDL remains above threshold. Currently, we have ezetimibe and PCSK9 monoclonal antibodies that are recommended to add to statin therapy if further LDL reduction is needed, but perhaps we’ll have new agents like evinacumab in the future that can do that as well.”