Rare Disease Report

Amgen's HoFH and HeFH Phase 3 Data Published

OCTOBER 02, 2014
James Radke

This week in The Lancet,  data from two phase 3 studies were published examining the safety and efficacy of Amgen’s evolocumab, a novel investigational low-density lipoprotein cholesterol (LDL-C)-lowering medication, for the treatment of a rare lipid disease [homozygous familial hypercholesterolemia (HoFH)] and a more common one [heterozygous familial hypercholesterolemia (HeFH)].

The two studies, the TESLA and RUTHERFORD-2,  showed treatment with evolocumab to be safe and effective in both populations.

Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver's ability to remove LDL-C from the blood.

HoFH (TESLA) Study

The Phase 3 12-week, double-blind, randomized, placebo-controlled, multicenter TESLA Part B Trial evaluated evolocumab (420 mg subcutaneously monthly) compared to placebo in 49 adults and adolescents aged 12 years and over with HoFH (LDL-C >130 mg/dL) who were on a stable dose of statin therapy and other lipid-lowering medications and were not receiving apheresis. The primary endpoint was the percent reduction from baseline in LDL-C at week 12.

The study observed patients taking evolocumab plus a stable dose of statin therapy and other lipid-lowering medications significantly reduced LDL-C by 31% (95% CI, -44, -18, p<0.001) from baseline at week 12 compared to placebo.

The study also observed that in patients with at least one defective LDL receptor mutation, evolocumab reduced LDL-C by 41% (95 percent CI, -53, -28, p<0.0001) compared to placebo. The most common adverse events in the evolocumab-treated patients were upper respiratory tract infection, influenza, gastroenteritis and nasopharyngitis.


This phase 3 randomized, multicenter, double-blind, placebo-controlled trial evaluated the safety, tolerability and efficacy of evolocumab (140 mg subcutaneously every two weeks or 420 mg  monthly) compared to placebo in 329 patients with HeFH and an LDL-C ≥100 mg/dL who were on a stable dose of statin therapy and lipid-lowering medication. The co-primary endpoints were the percent reduction from baseline in LDL-C at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12.

The study showed that adding subcutaneous evolocumab (140 mg every two weeks or 420 mg monthly) to a stable dose of statin and other lipid-lowering therapies significantly reduced mean LDL-C by 59-66% from baseline compared to placebo at week 12 and weeks 10 and 12 (p<0.001). At week 12, an LDL-C level of 70 mg/dL (1.8 mmol/L) was achieved by 68%of patients treated with evolocumab 140 mg every two weeks and by 63% of patients treated with evolocumab 420 mg monthly, versus 2% of patients in the placebo groups (p<0.0001 each).  The most common adverse events reported in the evolocumab-treated patients were nasopharyngitis, headache, contusion (i.e., bruise), back pain and nausea

In a press release, Sean E. Harper, M.D., executive vice president of Research and Development at Amgen said:

"Results from these two Phase 3 studies support the effectiveness of evolocumab as a treatment option for patients with both forms of familial hypercholesterolemia, who struggle to manage their cholesterol levels."

"These results, in combination with data from a number of other studies in our clinical trial program, formed the basis of our U.S. and EU filing submissions for evolocumab and we are working with regulatory authorities to bring this important treatment option to patients with significant unmet medical need."

 Familial Hypercholesterolemia (FH) 

FH is a genetic condition that can be either heterozygous (HeFH), which is very common, or HoFH, which is very rare.

Common to both HoFH and HeFH are severe dyslipidemia (eg, low-density lipoprotein cholesterol [LDL-C] >190 mg/dL), early cardiovascular disease, cutaneous stigmata, and a family history. Where HoFH and HeFH differ is in the:
  • genetics (HoFH has two mutations of the LDL-R gene, HeFH has one)
  • prevalence (HoFH, 1 in 1 million; HeFH, 1 in 600)
  • severity (HoFH is a more serious condition, with death often occurring by age 20, if left untreated).

There are currently two orphan drugs approved for HoFH, Juxtapid (lomitapide) and Kynamro (mipomerson).


Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. The Lancet. 2014 [Epub ahead of print]. doi:10.1016/S0140-6736(14)61374-X

Raal FJ, Steiin EA, Dufour R, et al.  PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. The Lancet 2014 [Epub ahead of print] doi:10.1016/S0140-6736(14)61399-4

Stay informed on the latest rare disease news and developments by signing up for our newsletter.
Copyright © RareDR 2013-2018 Rare Disease Communications. All Rights Reserved.