(HealthDay News) — Evolocumab, a PCSK9 inhibitor, shows promise for patients with heterozygous or homozygous familial hypercholesterolemia, according to two studies published in The Lancet.

In the RUTHERFORD-2 study, Frederick J. Raal, PhD, from the University of Witwatersrand in Johannesburg, South Africa, and colleagues conducted a multicenter study involving 331 patients with heterozygous familial hypercholesterolemia on stable lipid-lowering therapy for at least 4 weeks.

Participants were randomly assigned to four treatment groups: evolocumab 140 mg every 2 weeks (n=111), evolocumab 420 mg monthly (n=110), placebo every 2 weeks (n=55) or placebo monthly (n=55).

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There were significant reductions in the mean LDL cholesterol at week 12 with both dosing schedules of evolocumab vs. placebo. Evolocumab was well tolerated, with adverse events at a similar rate to placebo.

In a second study — TESLA Part B — Raal and colleagues conducted a phase 3 trial at 17 sites in 10 countries involving 49 patients with homozygous familial hypercholesterolemia on stable lipid-regulating therapy.

Participants were randomly assigned to evolocumab 420 mg (n=33) or placebo (n=16) every 4 weeks.

The researchers found that evolocumab significantly reduced ultracentrifugation LDL cholesterol by week 12 by 30.9% compared with placebo (P<.001). In 63% and 36% of the placebo and evolocumab groups, respectively, treatment-emergent adverse events occurred.

“In patients with homozygous familial hypercholesterolemia receiving stable background lipid-lowering treatment and not on apheresis, evolocumab 420 mg administered every 4 weeks was well tolerated and significantly reduced LDL cholesterol compared with placebo,” the researchers wrote in the second study.

“Our results indicate that evolocumab achieves similar cholesterol reductions but with a more rapid onset of action and fewer side effects than two drugs recently approved as orphan therapies for homozygous familial hypercholesterolemia — mipomersen and lomitapide,” co-lead author Evan Stein, MD, PhD, from the Metabolic and Atherosclerosis Research Center in Cincinnati, Missouri, said in a press release.

In a linked comment, Raul Santos, MD, MSc, PhD, from the University of Sao Paulo Medical School Hospital in Brazil, and Gerald Watts, MD, PhD, from the University of Western Australia in Perth, wrote:

“If proven to be safe and efficacious in the long term, as well as cost effective, PCSK9 monoclonal antibodies might be the standard of care for many patients with severe forms of familial hypercholesterolemia … However, the wider applications of PCSK9 monoclonal antibodies as an additional therapy to statins will depend on the results of large clinical outcome trials, such as ODYSSEY with alirocumab, FOURIER with evolocumab, and SPIRE-1 and SPIRE-2 with bococizumab, that are underway in patients at high risk of cardiovascular disease.”

Several authors from both studies disclosed financial ties to pharmaceutical and biotechnology companies, including Amgen, which manufactures evolocumab and funded the study.


  1. Raal FJ et al. Lancet. 2014;doi:10.1016/S0140-6736(14)61399-4.
  2. Raal FJ et al. Lancet. 2014;doi:10.1016/S0140-6736(14)61374-X.
  3. Santos RD, Watts GF. Lancet. 2014;doi:10.1016/S0140-6736(14)61702-5.