The addition of LY3015014, an investigational PCSK9 inhibitor, to standard lipid-lowering therapy may be safe and effective when administered every 4 to 8 weeks to patients with hypercholesterolemia, according to new phase 2 data.
John J.P. Kastelein, MD, professor of medicine and strategic chair of genetics of cardiovascular disease, department of vascular medicine at the Academic Medical Center of the University of Amsterdam, and colleagues conducted a double blind, parallel, placebo-controlled trial from June 2013 to January 2014 in which 527 patients with primary hypercholesterolemia at 61 centers in North America, Europe and Japan were randomly assigned to receive subcutaneous injections of 20 mg, 120 mg or 300 mg LY3015014 (Eli Lilly) every 4 weeks; 100 mg or 300 mg every 8 weeks; or placebo every 4 weeks.
John J.P. Kastelein
The patients were primarily male (53.6%) and white (68.6%), and the mean age was 58 years. Ten percent of patients were simultaneously receiving atorvastatin 40 mg to 80 mg or rosuvastatin (Crestor, AstraZeneca) 20 mg to 40 mg. Seventy percent of patients were taking another type of statin, whereas 20.2% were not using a statin at all. Ezetimibe (Zetia, Merck) was used by 14% of patients.
The primary outcome was change in LDL by week 16. Kastelein and colleagues observed a maximum reduction of 50.5% in those patients assigned 300 mg every 4 weeks and 37.1% in those patients assigned 300 mg every 8 weeks compared with a 7.6% increase in the placebo group. In addition, findings revealed that patients also taking statins had a greater reduction in LDL compared with those who were not receiving concomitant statin therapy (P = .006). Male sex was also associated with greater efficacy except for those patients assigned 100 mg every 8 weeks.
No serious treatment-related adverse events occurred. Injection-site pain and erythema were more common in the treatment groups than in the placebo group. Of the 527 patients, 21 (4%) discontinued the study due to an adverse event, three of which were injection-site related. One death from sudden cardiac arrest occurred within the placebo group. No concerns with liver toxicity or the skeletal muscle were revealed.
Kastelein and colleagues called for future research to evaluate the long-term safety and CV effects of LY3015014. – by Tracey Romero
Disclosure: Eli Lilly funded the study. Kastelein reports receiving consultant fees and/or honoraria from Aegerion, Amgen, AstraZeneca, AtheroNova, Boehringer Ingelheim, Catabasis, Cerenis, CSL Behring, Dezima Pharmaceuticals, Eli Lilly, Esperion, Genzyme, Ionis, Kowa, Merck, Novartis, Omthera, Pronova, Regeneron, Sanofi, The Medicines Company, UniQure and Vascular Biogenics. Please see the full study for a list of all other researchers’ relevant financial disclosures.