#ACC21: Regeneron's Evkeeza shows promise in curbing high triglycerides, but will genetic disparities limit use?
When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?
Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.
The data are a promising sign that Regeneron’s antibody can add on to its label after an initial FDA approval in a rare disease causing abnormally high cholesterol, dubbed homozygous familial hypercholesterolemia, back in February. The drug is approved as a supplement to standard-of-care LDL lowering therapies such as statins.
Evkeeza’s win in Phase II looks like a promising sign of its promise in front of regulators, but patients’ genetic profiles showed a big disparity in terms of the drug’s effect on curbing triglycerides. In patients with a double copy of certain mutations in the LPL pathway, which regulates cholesterol and triglycerides, Evkeeza “had essentially no benefit,” researchers said. Meanwhile, patients with one copy of an LPL mutation or no mutations saw triglyceride reductions around 80%.
Patients with no mutations taken alone posted a mean reduction in triglycerides of 27.1% and a median reduction of 68.8%.
With those results in mind, researchers think Evkeeza could prove to be an effective therapy for severe hypertriglyceridemia given an appropriate genetic profile. Meanwhile, patients with double copies of LPL pathway mutation will be left to look for other options.
“(This study) demonstrates the importance of genetic testing in people with severe hypertriglyceridemia because by performing genetic testing you are able to tell which individuals will respond to this therapy and which are unlikely to respond,” lead author Robert Rosenson said in a statement.
The Phase II study enrolled 51 patients with the disorder at 17 sites in four countries in North America and Europe, according to a release. Regeneron plans to try Evkeeza in larger studies to determine effect across a broader patient pool. By showing early benefit lowering both LDL and triglycerides, Regeneron thinks Evkeeza could have some effect in diseases like diabetes and heart disease characterized by high levels of both lipids.
“By lowering triglycerides by 60-80% and LDL cholesterol by 50% on top of statins and other medications, this agent has an opportunity to impact cardiovascular disease in these very high-risk individuals,” Rosenson said.