Regeneron’s new med Evkeeza already sports an approval in the ultra-rare disease homozygous familial hypercholesterolemia, which is associated with extreme levels of cholesterol. But thanks to competition in the field, it’s not expected to make a big splash, sale-wise.
Now, though, Evkeeza boasts data that could help it garner bigger approval in severe hypertriglyceridemia—provided it can find the right patients to target.
In a phase 2 study presented Sunday at the American College of Cardiology’s annual scientific session, Evkeeza helped reduce patients’ triglyceride levels by 57% at median after 12 weeks, compared with an overall increase of 1.8% for patients taking placebo.
But the drug worked far better in patients with certain genetic characteristics and essentially didn’t work at all in others, suggesting that doctors could test patients to identify who's likely to respond before starting treatment, researchers said.
“One of the very important findings in this trial is that by genotyping patients with severe hypertriglyceridemia,” doctors are able to identify people who will respond “very well” to the medicine, lead author Robert Rosenson, M.D., said in an interview. Rosenson is a professor of medicine in cardiology and the director of metabolism and lipids at the Mount Sinai Health System
Investigators recruited 51 patients in North America and Europe with triglyceride levels of 500 mg/dL or higher despite maintaining a strict diet. The patients also had a prior hospitalization for acute pancreatitis, a common complication of severe hypertriglyceridemia. Two-thirds of patients received the Regeneron drug for 24 weeks, while one-third received a placebo for the first 12 weeks and then Evkeeza for the second 12 weeks.
For patients with a double copy of certain mutations in LPL pathway genes, trial investigators found “essentially no benefit” from the treatment. Among those with a single mutation in LPL pathway genes—or no mutations—investigators recorded triglyceride reductions of around 80%.
Evkeeza, also known as evinacumab, scored an FDA approval in February to treat homozygous familial hypercholesterolemia, an ultra-rare disease that affects about 1,300 people in the U.S. In that indication, the medicine bears a list price of $450,000 a year, and it’s going up against Amgen’s PCSK9 drug Repatha, a mass market med carrying a much lower price.
Plus, Regeneron’s own PCSK9 drug Praluent scored an FDA approval in that use back in April. And Novartis is running studies of its PCSK9 inhibitor inclisiran in familial hypercholesterolemia.
Evkeeza works differently, however; it binds to the angiopoietin-like protein 3, which regulates cholesterol and triglycerides. Evercore ISI analysts have projected the drug can reach peak sales of $200 million to $400 million.
It isn't clear how Regeneron would price the drug in severe hypertriglyceridemia, which affects millions of Americans, rather than the 1,300 who have homozygous familial hypercholesterolemia, according to one study. Regeneron hasn't yet said whether it plans to take Evkeeza into phase 3 testing for hypertriglyceridemia.
Up ahead are potential Evkeeza studies at a higher dose and in patients with elevated triglycerides and LDL cholesterol.
Current treatment options for severe hypertriglyceridemia include fibrates, omega-3 fatty acids and insulin. Patients with the disease “suffer immensely” and face high risks of hospitalizations for pancreatitis, Rosenson said. They often respond “inadequately” to existing medicines, he added.
“Each and every effort that we can make to prevent recurrent pancreatitis is important for the quality of life and survival for these patients,” he said.
In the study, patients in both the Evkeeza and placebo groups experienced abdominal pain, acute pancreatitis and headaches. Most cases of acute pancreatitis were seen in the placebo group or occurred more than four weeks after patients stopped taking Evkeeza, researchers said.