• Regeneron Pharmaceuticals said its experimental drug evinacumab significantly lowered “bad” cholesterol levels 49% compared to placebo in a Phase 3 study of patients with homozygous familial hypercholesterolemia (HoFH), a severe form of disease resistant to treatment.
• The data may help Regeneron expand its cardiovascular franchise as Praluent, its marketed drug co-developed with Sanofi, is not labeled specifically for use in this population. Repatha, a rival therapy from, Amgen, can be used to treat HoFH in conjunction with other interventions.
• Investors have been looking for positive data from the evinacumab trial and several other Regeneron pipeline assets to help diversify its revenue streams away from Eylea and Dupixent.

HoFH is a rare disease affecting about 1,300 in the United States, and is especially resistant to treatment. Patients sometimes have to undergo an invasive procedure called apheresis in which low-density lipoprotein, the so-called bad cholesterol, gets filtered from their blood.

Repatha (evolocumab), a PCSK9 inhibitor, can be used in conjunction with diet, oral LDL-lowering treatments and apheresis to provide additional cholesterol reduction. Regeneron’s Praluent (alirocumab), meanwhile, has only received approval to treat patients with the less severe heterozygous form known as HeFH.

Evinacumab targets a different biological pathway called ANGPTL3. Scientists have shown that people with deficiencies in this protein have less coronary arterial disease.

The trial enrolled 65 HoFH patients who, on average, had LDL levels of 255 mg/dl — two and a half times that of a healthy individual — in spite of treatment with statins, Zetia, a PCSK9 inhibitor and apheresis. After 24 weeks of treatment, patients randomized to take evinacumab saw their cholesterol fall 47%, while those taking placebo saw it rise 2%.

The absolute LDL change in the evinacumab patients was a reduction of 132 mg/dl.

The FDA has granted evinacumab Breakthrough Therapy designation, and Regeneron expects to submit it for approval in 2020. The company is working on other evinacumab as well, including Phase 2 studies in HeFH and severe heart disease patients and those with elevated triglycerides at risk for pancreatitis.

As a drug to treat an orphan disease, evinacumab could command a high price. Payers asked to reimburse Regeneron will be eager to see additional outcomes data showing that its potent LDL-lowering effects also translate into reduction of cardiovascular events, less frequent or elimination of apheresis or discontinuation of other drugs.

Regeneron spokesperson Sarah Cornhill told BioPharma Dive the company has no plans to initiate clinical trials of evinacumab in the much broader population of patients with LDL elevations currently treated with statins, Repatha or Praluent.