Patients with familial hypercholesterolemia given a monoclonal antibody had a 30.9 percent reduction in low-density lipoprotein (LDL) concentrations after 12 weeks in a study published Oct. 2 in The Lancet.

Evolocumab (Amgen) affects receptors for proprotein convertase subtilisin/kexin type 9 (PCSK9), acting as an antibody to improve function of defective LDL receptors, classically found in patients with familial hypercholesterolemia. These patients have difficulty controlling genetically high concentrations of LDL even with a statin regimen. Most are still children when they begin to experience cardiovascular diseases and degradation due to blood cholesterol levels.

Frederick J. Raal, PhD, of the University of Witwatersrand in Johannesburg, South Africa, and colleagues developed the TESLA Part B trial to determine the drug’s efficacy in a phase 3 trial. Fifty patients with familial hypercholesterolemia on stable lipid-lowering medication were randomized between use of the PCSK9 antibody or a placebo.

Patients given evolocumab had ultracentrifugation LDL cholesterol reduced by 30.9 percent in 12 weeks compared with the placebo. However, Raal et al noted that effectiveness was relative to the number of LDL receptor mutations patients had, with the greatest mean apolipoproteib B reduction by week 12 seen in patients with defects in both alleles as opposed to those who had one defective and one negative mutation.

No differences were noted between placebo and evolocumab patients in terms of HDL cholesterol or triglycerides at week 12. Also, lipoprotein (a) was not significantly reduced in any patient.

Raal et al found a 32.1 percent reduction in unbound PCSK9 between baseline and week four and 90.1 percent by week six.

No serious adverse events were reported, but 63 percent of placebo patients and 36 of evolocumab patients had treatment-emergent adverse events.

“This trial shows that genetic information provides incremental insight into homozygous familial hypercholesterolaemia and possible response to treatment,” Raal et al wrote. “Therefore, in a clinical trial setting, to obtain genetic confirmation for homozygous familial hypercholesterolaemia is valuable and could be useful to select patients for evolocumab treatment in clinical practice.”

While this and other studies have been small thus far, there are members of the community who think that these findings hold promise in treating these high-risk patients.

Raul D Santos, MD, PhD, MSc, of the University of Sao Paulo Medical School Hospital and the Hospital Israelita Albert Einstein in Sao Paulo, Brazil, and colleague Gerald F. Watts, DSc, MD, PhD, of the Royal Perth Hospital at the University of Western Australia, wrote in an editorial, “If proven to be safe and efficacious in the long term, as well as cost effective, PCSK9 monoclonal antibodies might be the best standard of care for many patients with severe forms of familial hypercholesterolaemia. This treatment could also apply to a wider range of high-risk patients with polygenic hypercholesterolaemia, including those with statin myopathy.”

This study was funded by Amgen.