Positive interim data from Phase II PoC study of evinacumab in patients with HoFH

Interim data from the first four patients treated in this study showed that evinacumab added to current lipid-lowering therapy reduced low-density lipoprotein cholesterol levels by an additional 55% at week 4 compared to baseline.

HoFH is the most severe form of hypercholesterolemia. While rare, occurring in approximately 1 to 2 people per million, untreated patients can have "bad cholesterol" or LDL-C levels ranging from 500 to 1000 mg/dL, compared to normal LDL-C levels of less than 130 mg/dL. Due to these high levels of LDL-C, patients with HoFH are at an extreme risk of premature cardiovascular disease. Without treatment, patients typically present with signs and symptoms of atherosclerotic cardiovascular disease before the age of 20.

"HoFH patients are not as responsive to traditional lipid lowering therapies like statins, and use of some new treatment options can be limited by safety and tolerability concerns," said Bill Sasiela, Vice President, Program Direction, Regeneron. "Preliminary data from this ongoing study show that evinacumab reduced LDL-C when combined with other lipid-lowering therapies, and suggests that ANGPTL3 is a new and exciting target that we look forward to exploring further in additional clinical trials."

The ongoing single-arm, open label, proof-of-concept study is targeting to enroll up to eight patients with HoFH. Study patients' diagnosis is confirmed both genetically and phenotypically. Current lipid-lowering therapy was maintained from 4 weeks before baseline through the 26-week treatment and observation period. Patients on LDL apheresis within 4 weeks prior to screening were excluded. For the 4 patients reported here, all were receiving maximum doses of statin plus ezetimibe with one patient additionally receiving lomitapide 20 mg. Evinacumab was dosed as a single 250 mg subcutaneous injection at baseline and subsequently, at week 2, as a 15 mg/kg intravenous (IV) infusion. The primary endpoint of the study was the mean percent change in LDL-C levels from baseline to week 4.

After 4 weeks of treatment and 2 weeks after administration of the 15 mg/kg IV dose, the mean reduction in LDL-C in the 4 patients was 55% (primary endpoint of the study). Among these 4 patients, the percent reductions in LDL-C ranged from 25 to 90%. Overall, the patients enrolled in the study saw their mean LDL-C levels fall from 331 mg/dL at baseline to 175 mg/dL at week 4.

Evinacumab was generally well tolerated and there were no adverse events leading to discontinuation. The most common drug-related adverse events were injection-site reactions, which were mild in severity.