ESCAPE - Effect of alirocumab on the frequency of lipoprotein apheresis: a randomised Phase III trial

Presented at the ESC congress 2016 by: Patrick Moriarty (Kansas City, KA, USA)

Background

Untreated familial hypercholesterolaemia (heFH) is associated with severely elevated LDL-c levels and a high risk of premature CHD. Despite LDL-c-lowering drug therapy, many patients with FH do not reach their target LDL-c levels. Lipoprotein apheresis (LA) effectively removes LDL-c by 50-75% and is considered as lipid-lowering option if LDL-c levels are not adequately lowered with maximally tolerated drug therapy. The procedure is time-consuming (up to 4 hours, performed weekly or biweekly) and costly, and can only be performed in specialised clinics.
The ODYSSEY-ESCAPE was designed to study whether adding the fully human monoclonal antibody directed at PCSK9 alirocumab to LA therapy could reduce or eliminate apheresis therapy. Male and female HeFH patients >18 years old undergoing weekly or biweekly LA were randomised to treatment with alirocumab 150 mg Q2W s.c. or placebo Q2W s.c. for 18 weeks (double-blind). During the first 6 weeks of this treatment period, frequency of LA was fixed, and in the last 12 weeks LA was only performed if LDL-c was <30% lower than at baseline LDL (pre-apheresis). During an 8-week follow-up period all patients received alirocumab 150 mg Q2W s.c.
Patients were on stable background therapy and had undergone consistent LA weekly for at least 4 weeks or biweekly for at least 8 weeks. The primary efficacy endpoint was frequency of apheresis treatment over 12 weeks, normalised according to the number of planned sessions.

Main results

• 63.4% of patients on alirocumab did not undergo any apheresis treatments between week 7 and week 18. In placebo-treated patients, no one skipped all treatments in this period.
• 17.1% of patients on alirocumab had a standard apheresis rate between 0 and 0.25.
• 12.2% of patients on alirocumab and 14.3% on placebo had a standardised apheresis rate between 0.25 and 0.5.
• 2.4% of patients on alirocumab and 23.8% on placebo had a standardised apheresis rate between 0.5 and 0.75.
• 2.4% of patients on alirocumab and 33.3% on placebo had a standardised apheresis rate between 0.75 and 1.
• 2.4% of patients on alirocumab and 28.6% on placebo had a standardised apheresis rate of 1.
• Least-square mean of time-averaged percentage change from baseline was -53.7 (SE: 2.3) with alirocumab and 1.6 (SE: 3.1) with placebo at week 6 (P<0.0001 for difference) and -42.5 (SE: 4.7) and 3.9 (SE: 6.3) respectively at week 18.
• Any treatment-emergent adverse events (AEs) were seen in 31 of 41 patients on alirocumab (75.6%) and in 16 of 21 on placebo (76.2%). Serious AEs were seen in 4 patients on alirocumab (9.8%) and in 2 on placebo (9.5%).

Conclusion

In ODYSSEY ESCAPE, alirocumab significantly reduced the frequency of lipoprotein apheresis in patients with HeFH who were not achieving recommended LDL-C levels without this treatment. Lipoprotein apheresis was discontinued in 63.4% of patients receiving alirocumab who were
previously undergoing regular apheresis. 92.7% of patients on alirocumab received at most half of their usual LA treatments.

Our reporting is based on the information provided during the ESC congress