Patients with heterozygous familial hypercholesterolaemia (HeFH) who rely on apheresis treatments for lipid control can significantly decrease or even eliminate this expensive and time-consuming procedure with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab, according to a phase III trial reported at the European Society of Cardiology (ESC) Congress 2016 held recently in Rome, Italy. [Eur Heart J 2016, doi: 10.1093/eurheartj/ehw388] 

“HeFH is associated with abnormally raised LDL-cholesterol [LDL-C] and lipoprotein(a) [Lp(a)] levels and a high risk of premature CVD, but many HeFH patients do not reach their target LDL-C levels despite intensive lipid-lowering therapy,” said lead study investigator, Dr. Patrick Moriarty from the University of Kansas, Kansas City, Missouri, US.

Lipoprotein apheresis acutely lowers LDL-C and Lp(a) levels by 50 to 75 percent, translating into an average 30 percent reduction between procedures. [Eur Heart J 2013;34:3478-3490] “However, the procedure can only be performed in specialized apheresis centres. It’s costly, and takes 3 to 4 hours weekly or fortnightly,” he noted.

The ODYSSEY ESCAPE study evaluated the effect of alirocumab Q2W on apheresis frequency in patients with HeFH. Alirocumab had previously demonstrated significant benefits in the phase III ODYSSEY programme, reducing LDL-C levels by about 60 percent as monotherapy or on a background of statins with or without other lipid-lowering drugs, in patients with or without HeFH. [N Engl J Med 2015;372:1489-1499; Eur Heart J 2015;36:1186-1194; Eur Heart J 2015;36:2996-3003]

The study enrolled 62 HeFH patients who were undergoing QW or Q2W lipoprotein apheresis at 14 study sites in the US and Germany. Patients were randomized to receive subcutaneous injections of either alirocumab (n=41) or placebo (n=21) Q2W for 18 weeks while continuing their regular lipid-lowering medications. Patient characteristics in terms of age, gender, frequency of apheresis, presence of cardiovascular disease, and background lipid-modifying therapy at baseline were well matched between the study groups. 

Until week 6, patients received apheresis treatments according to their established schedule, which was then adjusted between weeks 7 and 18 based on their individual needs. If their LDL-C had dropped by ≥30 percent from baseline level, apheresis was skipped. The primary efficacy endpoint was frequency of apheresis over 12 weeks. Secondary endpoints included the effect of alirocumab on other lipids, safety and tolerability.

“In total, 63.4 percent of patients on alirocumab eliminated apheresis altogether vs none in the placebo group, and 92.7 percent avoided at least half of the procedures vs 14.3 percent of those on placebo. At study end, alirocumab-treated patients had a 75 percent greater reduction in apheresis rate compared with those on placebo,” reported Moriarty.

As expected, alirocumab significantly reduced LDL-C levels by 42-54 percent (p<0.0001 vs placebo)

Alirocumab was well tolerated and the incidence of treatment-emergent adverse events was similar between the alirocumab and placebo groups.

“Alirocumab is already approved for use in HeFH and high-risk CVD patients, and can now be considered as part of standard care for treatment-resistant HeFH. Being able to reduce or eliminate apheresis would be a major breakthrough for these patients,” said Moriarty. 

“Given the small sample size, larger studies are needed to confirm these results. Clinical practice will show how many HeFH patients can really stop apheresis and reach their LDL-C targets,” commented discussant Dr. Eric Bruckert of the Pitie-Salpetriere Hospital, Paris, France.