Regeneron has a new approved drug to add to its stable of monoclonal antibodies.
The FDA gave the thumbs-up to the biotech’s evinacumab, to be called Evkeeza, as a supplement to other LDL-lowering treatments for the rare genetic disorder homozygous familial hypercholesterolemia. Evkeeza has been indicated for patients older than 12 and is priced based on weight, but Regeneron expects it will cost an average of $450,000 per year.
HoFH is part of a family of disorders that affect the body’s ability to break down LDL cholesterol, Evkeeza trial clinician and cardiologist Seth Baum told Endpoints News. Doctors believe the disease affects about 1,300 patients in the US, but Baum said it’s difficult to know the exact number because for years the disease was not thought to be different from its cousin, heterozygous familial hypercholesterolemia.
Whereas patients with the heterozygous form of the disorder only need the malfunctioning gene from one parent, homozygous patients get the mutation from both. In many HoFH patients, typical cholesterol-lowering treatments like statins and PCSK9 inhibitors are essentially useless, and in the most difficult to treat population — called “null/null” — LDL receptors in the liver barely function at all.
That usually leads to LDL cholesterol levels in the range of 400 to 500 mg/dL, with the levels sometimes reaching 1,000. The average American, meanwhile, has LDL levels of 112 mg/dL, Baum said, meaning HoFH patients can be highly susceptible to premature heart disease before the age of 10.
Evkeeza is not indicated for individuals with heterozygous familial hypercholesterolemia, and the effect of Evkeeza on cardiovascular morbidity and mortality has not been determined. The drug works by blocking the function of angiopoietin-like 3, a protein that plays a key role in lipid metabolism. Regeneron says it’s the first FDA-approved medication to block this protein.
In Regeneron’s pivotal study upon which Thursday’s approval is based, the company enrolled 65 patients who were already on maximally tolerated lipid-lowering therapies. These individuals had failed on all other therapies, and were randomized 2-to-1 to the drug arm.
Patients taking Evkeeza saw a 47% reduction in LDL levels from baseline, compared to a 2% increase in the control. The drug arm also saw significant reductions in levels of apolipoprotein B, an indicator of vascular disease, as well as triglycerides and overall cholesterol.
The most common side effects that occurred more often in the Evkeeza arm were incidents of the common cold, flu-like illness, dizziness and runny nose. During the double-blinded portion of the trial, 66% of evinacumab patients and 81% of placebo patients experienced at least one adverse event.
It’s another weapon for Regeneron in the cholesterol arena, which already has an approved PCSK9 inhibitor in Praluent. Originally OK’ed back in 2015, Praluent saw a lower-than-expected uptake after the initial price resulted in some sticker shock. Praluent and Amgen’s Repatha, the other big PCSK9 drug on the market, engaged in a sparring match with insurers as a result — their prices were slashed to $5,850 in October 2018 after insurers won that battle. But PCSK9 drugs aren’t the only cholesterol-lowering meds out here, as Esperion recently launched Nexlizet as a once-daily pill and a cheaper option to the antibodies.
Evkeeza is also the next in a long line of antibody treatments that have come from Regeneron’s genetically-engineered mouse platform, a list that includes Praluent, Kevzara, Libtayo and the blockbuster Dupixent. Those four drugs pulled in nearly $4 billion for the biotech in 2020, though the vast majority came from Dupixent sales.