Regeneron preps for 2020 filing for new cholesterol drug after trial success

Regeneron has announced data that could create a niche for its latest cholesterol drug evinacumab in a small group of patients who do not respond to the strongest available medicines.

The US pharma is developing evinacumab to treat patients with homozygous familial hypercholesterolaemia (HoFH), with high levels of “bad” low-density lipoprotein (LDL) cholesterol despite treatment with other lipid-lowering therapies including maximum statin doses, and PCSK9 inhibitors.

HoFH affects only 1,300 people in the US, but those affected often experience early atherosclerotic disease and sometimes suffer cardiac events as early as their teenage years.

Despite this tiny patient population there is already talk of peak US sales in the region of $200 million to $400 million.

The latest trial was asking whether evinacumab can cut cholesterol levels after PCSK9 drugs such as Sanofi/Regeneron’s Praluent (alirocumab) and Amgen’s Repatha (evolocumab) have failed.

Patients had also been treated with therapies including ezetimibe, LDL apheresis, and lomitapide.

According to the phase 3 ELIPSE HoFH trial, the answer to this question is “yes” – adding evinacumab to other lipid-lowering therapies decreased LDL cholesterol by 49% on average, compared with lipid lowering therapies alone.

Patients entered the trial with LDL cholesterol levels of 255 mg/dL despite treatment with available therapies.

There was a 132 mg/dL absolute change in LDL cholesterol from baseline compared with placebo and 47% achieved cholesterol levels less than 100 mh/dL compared with 23% for placebo.

Similar levels of LDL cholesterol-lowering were also observed in the most difficult-to-treat patients who often don't respond to certain other therapies, described as "null/null" or "negative/negative" patients.

Evinacumab also reduced apolipoprotein B (ApoB), non-HDL cholesterol and total cholesterol compared to placebo.

In 2017 the FDA granted the drug Breakthrough Therapy designation for hypercholesterolaemia in patients with HoFH.

This paves the way for a potential fast review when Regeneron files data from this and other evinacumab trials with the regulator next year.