By MATTHEW HERPER @matthewherper and DAMIAN GARDE @damiangardeAUGUST 14, 2019

Regeneron Pharmaceuticals (REGN) presented new data Wednesday showing a drug it developed can treat patients with a genetic disease that causes very high cholesterol levels.

In homozygous familial hypercholesterolemia, or HoFH, patients can have levels of low-density lipoprotein of 500 milligrams per deciliter or more, five times normal levels, and can have heart attacks or other cardiovascular problems in their 20s. The disorder, which results from having two non-functioning copies of the LDL receptor gene that is involved in removing cholesterol from the blood, afflicts about 1,300 patients in the United States.

The Regeneron medicine, evinacumab, lowered LDL cholesterol 47%, on average, compared to a 2% increase for patients on placebo, according to a 65-patient study. Compared to placebo, there was a 132 mg/dL absolute change in LDL, with 47% of patients on the drug achieving LDL cholesterol levels below 100 mg/dL, the upper bound of what’s considered healthy. Only 23% of the patients in the placebo group achieved LDL levels below 100 mg/dL.

In patients with the most severe form of this severe disease — those with no function at all in both of their LDL receptor genes — the drug was as effective as in other types of patients. These patients often don’t respond to other therapies.

Adverse events occurred in 66% of evinacumab patients and 81% of those on placebo, but people on evinacumab were more likely to describe flu-like illness or a runny nose. There was no difference in nausea, abdominal pain, diarrhea, heart problems, liver disorders, or deaths.

Evinacumab, an intravenous antibody therapy, emerged from Regeneron’s large-scale DNA-sequencing efforts. In a paper published in the New England Journal of Medicine in 2017, Regeneron researchers described how variants in a gene for a protein called angiopoietin-like 3, or ANGPTL3, can result in lower cholesterol levels. The work resulted in part from Regeneron’s collaboration with the Geisinger Health System.

Before the data were released, investors already questioned whether this impressively rapid drug development would amount to much in the way of financial returns.

“The bigger question relates to market sizing given that there are several suitable options” for the disease, Cowen analyst Yaron Werber wrote in a note to clients last week.

Among them is Regeneron’s own Praluent, a cholesterol-lowering injection marketed alongside Sanofi (SNY), and Repatha, a similar therapy sold by Amgen (AMGN). Each used to carry a list of price of roughly $14,000 a year, but payer pushback led the manufacturers to bring the effective cost down to about $6,000. And each is used for patients with HoFH, although they are not effective for many patients, particularly those with no function on either LDL receptor gene, called “null nulls.”

That means evinacumab is likely to be relegated only for patients with HoFH whose cholesterol stays dangerously high despite all available treatment, according to Werber. And it means Regeneron will need to charge a six-figure price to turn the antibody into a successful product.

Marketing drugs for HoFH has proved challenging in the past. Juxtapid, an oral treatment for HoFH approved in 2012, carries a list price above $300,000 and has never been a commercial success, bringing in about $59 million for manufacturer Novelion Therapeutics (NVLN) in 2018. Kynamro, a weekly injection from Ionis Pharmaceuticals (IONS) approved in 2013, was a commercial non-starter and has since changed hands twice.

Each of those treatments also carried an FDA-mandated black box on its label, warning of potential liver damage. Evinacumab appears to be free of such serious side effects.