02 Oct Evolocumab For Resistant Familial Hypercholesterolemia

MedicalResearch.com Interview with:
Dr. Raul Santos
Unidade Clínica de Lipides InCor-HCFMUSP
Sao Paulo, Brazil.

Medical Research: What are the main findings of the study?

Dr. Santos: Evolocumab 420 mg injected subcutaneously every 4 weeks reduced LDL-C by 31% on average, in relation to placebo, in Homozygous familial hypercholesterolemia patients that were using maximally tolerated lipid lowering therapy but not on lipid apheresis regimen. Patients were separated according to the type of LDL receptor mutation, those with at least one allele codifyng a defective mutation on the LDL receptor (residual receptor activity 2-25%) had on average a 41% reduction on LDL-cholesterol. The 2 patients  homozygotes with alleles that codify a null mutation )receptor activity < 2%), did not respond to treatment. This was expected since PCSK9 inhibitors need a functional LDL receptor do work. Basically they increase the expression of the receptor that facilitates the clearance from plasma of circulating LDL particles. In those patients with defective LDL receptor  mutations there was 24% reduction of lipoprotein(a) concentrations, an extra risk factor for cardiovascular disease in familial hypercholesterolemia patients.

Medical Research: What was most surprising about the results?

Dr. Santos: The variability on the response to evolocumab treatment for patients bearing the same kind of LDL receptor mutations ; from -7% to -56% ; suggesting that there are mechanisms hitherto unknown that modulate the response to treatment.

Medical Research: What should clinicians and patients take away from your report? 

Dr. Santos: This study adds the possibility of an efficacious and highly tolerated treatment for homozygous familial hypercholesterolemia, a disorder where  cardiovascular disease and death usually occur within  the first 3 decades of life.

Medical Research:What recommendations do you have for future research as a result of this study?

Dr. Santos: We still need to know the long term efficacy and safety of this treatment. Also, the response to treatment in patients undergoing lipid apheresis needs to be studied. Finally, we still need to test the association of PCSK9 inhibitors with medications that block LDL production like mipomersen or lomitapide, since the average on treatment LDL-cholesterol level was still 7 mmol/L (around 280 mg/dL) a value still out of the recommended for and effective cardiovascular disease prevention.
Citation:

Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial

Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial
Prof Frederick J Raal PhD,Narimon Honarpour MD,Dirk J Blom MD,G Kees Hovingh MD,Feng Xu MS,Rob Scott MD,Scott M Wasserman MD,Prof Evan A Stein PhD,for the TESLA Investigators
The Lancet – 2 October 2014
DOI: 10.1016/S0140-6736(14)61374-X

Last Updated on October 2, 2014 by Marie Benz MD FAAD