Evolocumab (Repatha), a human monoclonal antibody and proprotein convertase subtilisin/kexin type 9 inhibitor, produced positive results in persons living with HIV in the BEIJERINCK study by reducing their levels of low-density lipoprotein cholesterol (LDL-C). These individuals have a risk of cardiovascular disease that is almost twice that of HIV-negative individuals.
In study results announced at ACC.20/WCC, held virtually this year due to the coronovirus disease 2019 (COVID-19) pandemic, evolocumab (Repatha), a human monoclonal antibody and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, was shown to have produced positive results in persons living with HIV in the EvolocumaB Effect on LDL-C LowerIng in SubJEcts with Human Immunodeficiency ViRus and INcreased Cardiovascular RisK (BEIJERINCK) study. It reduced their levels of low-density lipoprotein cholesterol (LDL-C).
These individuals have a risk of cardiovascular disease that is almost twice that of HIV-negative individuals. As a PCSK9 inhibitor, evolocumab binds to PCSK9, preventing it from blocking the removal of LDL-C, the bad cholesterol, from the blood.
According to David M. Reese, MD, executive vice president of research and development at Amgen, “Certain antiretroviral treatments for HIV can increase LDL-C and change the lipid makeup of people living with HIV.”
BEIJERINCK, a double-blind, randomized, placebo-controlled, 24-week study, evaluated a monthly dose of 420-mg evolocumab for safety and effectiveness among 467 individuals, at least 18 years of age, with an HIV viral load of 50 or fewer copies/mL or who also had hyperlipidemia or mixed dyslipidemia. These patients, who were enrolled from 75 sites in 15 countries between May 22, 2017, and January 23, 2019, had to have been receiving HIV therapy on a consistent basis for 6 months or more leading up to the study, as well as lipid-lowering therapy at the maximum tolerated dose for 4 or more weeks.
The primary end point was percent change in LDL-C from baseline to week 24, and secondary end points were LDL-C below 70 mg/dL or at least a 50% drop in LDL-C at week 24, change from baseline in LDL-C, and limiting treatment-emergent adverse events (TEAEs). Of the total 467 patients who qualified for the study, 464 completed it; 307 received evolocumab and 157, placebo.
There was a reduction in total LDL-C among the patients with HIV of more than 56% compared with the placebo group. Almost 72% of these patients also achieved the secondary outcome of at least a 50% reduction in their LDL-C from baseline to week 24, with just over 65% reaching an LDL-C measure below 70 mg/dL. Additional benefits include an increase in high-density lipoprotein cholesterol levels, as well as lower levels of triglycerides, both compared with the placebo group.
The most common TEAEs in the study and placebo cohorts were diarrhea (11 and 7, respectively) and back pain and influenza (12 and 4 each). Paresthesia only occurred in 7 patients in the study cohort.
"This is the first phase 3 study to demonstrate that a PCSK9 inhibitor can effectively and safely reduce LDL-C in people living with HIV at risk for cardiovascular disease who have high cholesterol level despite statin treatment. Addressing uncontrolled LDL-C in this high-risk patient population is critical to maintain the progress that has been achieved in improving the lives of people living with HIV," stated Franck Boccara, MD, PhD, cardiologist and primary study investigator, Sorbonne Université, Paris.
Kumar PN, Caramelli B, Calmy A, et al. Evolocumab use in HIV-infected patients with dyslipidemia: primary results of the randomized, double-blind BEIJERINCK study. Presented at: ACC.20/WCC Virtual Experience; March 28-30, 2020. cslide-us.ctimeetingtech.com/acc2020_eposter/attendee/eposter/poster/3715?q=BEIJERINCK. Accessed March 31, 2020.