Among patients with heterozygous familial hypercholesterolemia (HeFH), alirocumab was associated with a 75% reduction in  lipoprotein apheresis compared with placebo, according to results from the ODYSSEY ESCAPE trial.1

The findings were presented at the 2016 European Society of Cardiology congress in Rome2 and simultaneously published in the European Heart Journal.

Nearly two-thirds of patients assigned to alirocumab (63.4%), a fully human monoclonal antibody that binds PCSK9 and inhibits PCSK9-mediated hepatic catabolism of the low-density lipoprotein (LDL) receptor, discontinued apheresis. Researchers conducting the trial also found that, overall, 92.7% of patients assigned to alirocumab cut their use of lipoprotein apheresis by at least half.

Those patients had been receiving regular apheresis weekly or biweekly.

Patrick M. Moriarty, MD, director of Clinical Pharmacology at University of Kansas Medical Center and the study’s lead author, told Cardiology Advisor that patients with familial hypercholesterolemia have elevated LDL cholesterol (LDL-C) which cannot be reduced by medication alone, and these patients are at greater risk for premature onset of cardiovascular disease. If LDL-C is not controlled, adults with HeFH are at “very” high risk for a coronary event by age 50.

Dr Moriarty added that lipoprotein apheresis works to lower LDL-C in these patients, but it is invasive and requires 2 to 3 hours to administer every week or every 2 weeks. More research is needed, but PCSK9-inhibitors like alirocumab may be able to produce comparable results in less time and at a much lower cost to the patient.

“Lipoprotein apheresis can cost $70,000 per year, while this drug is $10,000 to $14,000. If we can eliminate or reduce the use of apheresis, that’s a win-win,” he said.

ODYSSEY ESCAPE was a randomized, double-blind, placebo-controlled, phase 3 trial conducted at 14 sites in the United States and Germany from March 2015 to September 2015. Patients with HeFH were assigned to biweekly subcutaneous 150 mg alirocumab (n=41) or placebo (n=21) for 18 weeks.

At 6 weeks, mean pre-apheresis LDL-C value decreased from 4.5 mmol/L (175 mg/dL) at baseline to 2.3 mmol/L (90 mg/dL) in the alirocumab group. By comparison, mean pre-apheresis LDL-C was 5.0 mmol/L (192 mg/dL) at baseline and and 4.8 mmol/L (185 mg/dL) at 6 weeks in placebo group.

In post hoc analysis, researchers found that time-averaged LDL-C values were consistently lower in the alirocumab group compared with the placebo group.

“The findings from this study suggest a role for alirocumab in the overall management of patients with HeFH undergoing regular lipoprotein apheresis therapy, with the potential to avoid apheresis treatments or delay the requirement for such treatments,” Dr Moriarty and investigators wrote.

Karol E. Watson, MD, PhD, director of the UCLA Barbra Streisand Women’s Heart Health Program and co-director of the UCLA Program in Preventive Cardiology, reviewed the results for Cardiology Advisor. She notedalirocumab produced good results in a patient population that can be challenging to treat.

“Patients with familial hypercholesterolaemia are some of the most difficult to treat because their LDL-C is so high,” she said. “For people who have familial hypercholesterolaemia who are already on apheresis, about 64% were able to discontinue the apheresis when they got the PCSK9-inhibitor. For a new group, the FH group, the results show a new benefit—patients can discontinue apheresis.”

Disclosures: Dr Moriarty has received grants and fees from Regeneron, Sanofi, Amgen, Ionis, Genzyme, Esperion, Eliaz Therapeutics, Alexion, Pfizer, Catabasis, Novartis, Kaneka, Aegerion, Amarin, and Eli Lilly. The other authors also reported fees and grants from the pharmaceutical industry.

For more information on ODYSSEY ESCAPE, please visit the trial page at ClinicalTrials.gov.

References

  1. Moriarty PM, Parhofer KG, Babirak SP, et al. Alirocumab in patients with heterozygous familial hypercholesterolemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J. 2016. doi:10.1093/eurheartj/ehw388.
  2. Moriarty PM, Parhofer KG, Babirak SP, et al; on behalf of the ODYSSEY ESCAPE Investigators. Abstract 5777. The ODYSSEY ESCAPE study: rationale, design, patient characteristics at baseline, and final study data. Presented at European Society of Cardiology. August 27-31, 2016; Rome, Italy.