Patients with high cholesterol stemming from a rare genetic disorder struggle to keep their cholesterol levels under control despite taking lipid-busting drugs such as statins and PCSK9 inhibitors. But a new drug from Regeneron may change that—the company unveiled new data Wednesday showing its latest cholesterol med cut “bad” cholesterol levels in half in this group of patients.
The phase 3 study tested the drug, evinacumab, in patients aged 12 to 75 with homozygous familial hypercholesterolemia (HoFH), which is marked by high levels of LDL, or “bad,” cholesterol. People with HoFH are often diagnosed in childhood or adolescence and develop heart disease at a very young age—typically before they turn 20.
The patients started the study with an average cholesterol level of 255 mg/dl—more than twice the Centers for Disease Control and Prevention’s recommended level of 100 mg/dl, Regeneron said in a statement. Their cholesterol remained high even though they were undergoing lipid-lowering treatments. Nearly all of them—98%—were on statins, while 82% were taking PCSK9 inhibitors—Amgen’s Repatha and Regeneron’s own Praluent—and 75% were on ezetimibe, a cholesterol-busting drug often prescribed with statins. More than one-third of the patients had the most severe form of HoFH, which often does not respond to other treatments.
Patients taking evinacumab alongside their usual lipid-lowering meds saw their “bad” cholesterol levels dive 49% from baseline compared to the placebo group: patients taking their regular drugs alone. In the evinacumab group, 47% of patients achieved the target LDL cholesterol level of less than 100 mg/dl, compared to just 23% in the placebo group.
"Currently HoFH patients face limited choices in reducing their LDL cholesterol, including therapies that are time-consuming like LDL apheresis, or that may have side effect concerns. Despite recent therapeutic advances, there is still a significant unmet need to lower the LDL cholesterol of many patients with HoFH. On average, evinacumab reduced patients' LDL cholesterol in half and was generally well-tolerated in the trial," said Regeneron Chief Scientific Officer George Yancopoulos, M.D., Ph.D., in the statement. "These results raise the potential that evinacumab may have value for other patients with severe, refractory hypercholesterolemia, where we have a trial ongoing."
Though evinacumab has the same R&D roots as Regeneron’s Sanofi-partnered Praluent, it works a little differently. While Praluent blocks PCSK9, evinacumab targets elevated triglycerides in the blood in addition to other lipids, such as LDL cholesterol. Specifically, it binds to angiopoietin-like protein 3 (ANGPTL3), which inhibits lipoprotein lipase (LPL), an enzyme that breaks down triglycerides and other lipids. Targeting triglycerides can tamp down inflammation of the pancreas as well as lower the risk of heart diseases such as atherosclerosis.
If approved, evinacumab could find a place right next to Praluent in Regeneron’s cardiovascular stable. Its ability to tackle both LDL cholesterol and triglycerides could boost its uptake—though, like PCSK9 inhibitors, it will have to compete with medicines that are already very cheap.
That said, the drug could find its niche in patients with HoFH for whom current treatments are inadequate. Evinacumab "could be combined with current oral medications for those patients with extraordinarily high triglycerides who often can't achieve safe levels with our usual medications," said Richard Dunbar, M.D., the lead investigator of a phase 1 study of evinacumab that read out in 2016.
The only question is, how high will Regeneron have to price the drug to recoup its R&D costs?