PCSK9 Inhibitor Alirocumab May Cut Reliance on Apheresis in FH

Larry Hand

August 29, 2016

ROME, ITALY — Alirocumab (Praluent, Sanofi/ Regeneron), when prescribed for patients with heterozygous familial hypercholesterolemia (HeFH), who normally undergo lipoprotein apheresis, may help them avoid or become less dependent on that treatment, according to new research presented at the European Society of Cardiology (ESC) 2016 Congress[1].

Alirocumab is a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor that is indicated for patients who don't achieve satisfactory levels of LDL cholesterol from statin therapy.

"I find that this class of drug is going to be very, very effective in treating this high-risk population," Dr Patrick M Moriarty (University Kansas Medical Center, Kansas City, KS) told heartwire from Medscape in an interview at the ESC congress on August 29, 2016.

Apheresis, which is done weekly or biweekly, costs $50,000 to $75,000 per year. The reason is the machines that are used; the kits are throwaways. "The supplies are costly. It's also time-consuming for nursing," he said.

Dr Patrick M Moriarty

"With this drug we have an opportunity now to eradicate apheresis totally for some of these patients and to reduce the amount of therapy from once a week to every 2 weeks. . . . By lowering that you're going to have a significant effect on cost and on patients' convenience," he continued, adding that the costs of the drug for his study were $7000 to $10,000 per year.

Moriarty and colleagues conducted the phase 3 ODYSSEY-ESCAPE trial involving 62 HeFH patients at 14 centers in the US and Germany who underwent apheresis either weekly or every 2 weeks.

The results were published simultaneously with the ESC congress presentation in the European Heart Journal.

In the study, researchers randomized the patients to receive alirocumab or placebo by subcutaneous injection (150 mg, n=41) or placebo (n=21) every 2 weeks for 18 weeks while still continuing regular lipid medications.

They administered apheresis treatment over 2 study phases: for 6 weeks according to the patient's established schedule, then adjusted for weeks 7 to 18 based on individual needs.

"After 6 weeks we evaluated who would need the apheresis further during that time period, compared with the placebo group," Moriarty said during his presentation. "If alirocumab could lower LDL at least 30%, then we don't need to treat with apheresis.

"Over 63% of patients did not need treatment with apheresis, because their LDL reductions were more than 30% compared with apheresis without the drug. Over 90% of patients had a more than 50% reduction of apheresis therapy over this 18-week period," he said.

In all, 92.7% of patients in the alirocumab group avoided at least half of apheresis treatments, compared with 14.3% of the placebo group.

The drug was generally safe and well tolerated.

Results Coming From Austria

Cardiologist and the primary investigator of a PCSK9 trial in Austria, Dr Heinz Drexel (Academic Teaching Hospital Feldkirch, Austria), ESC spokesperson, told heartwire , "We have had statins now for 25 years and have reduced LDL cholesterol a lot, but there is lots of residual disease. Now PCSK9 is a very strong class, and it's the next step in bringing LDL cholesterol to its natural value."

In Austria the drug costs run about €5000 a year, he said, adding that his trial will be over next year.

In a study earlier this month, researchers concluded that drug costs for PCSK9 inhibitors, which also included evolocumab (Repatha, Amgen), would have to be reduced by more than two-thirds to be cost-effective in treating general HeFH and atherosclerotic disease. That study had the annual cost at $14,350 in the US but less in Europe.

But Moriarty, who works at the largest apheresis-treatment center in the US, said that's not the case for this patient population.

"In this case, with the population, it's converse. It's the opposite. It's very much cost-effective," he said.

More, Not Less

In another presentation on apheresis in the same session, researchers pointed out a need for using more apheresis rather than less[2].

Dr Tina Khan (Royal Brompton & Harefield NHS Foundation Trust, London, UK), conducted an apheresis-procedure study involving 20 patients with angina refractory to medical therapy and revascularization.

They randomized the patients to receive lipoprotein apheresis or sham treatment for 3 months, then crossed them over for another 3 months after a 1-month washout period. Using cardiac magnetic resonance imaging, the researchers observed a significant increase in myocardial perfusion reserve after apheresis treatment compared with sham treatment (P<0.001).

Symptoms also improved in the treatment group compared with the sham group.

"Raised lipoprotein has been well established with a multitude of epidemiological evidence to be an independent primary cardiovascular risk factor and it can be effectively reduced by lipoprotein apheresis. It cannot be treated satisfactorily by our conventional therapies," Khan said.

"Raised lipoprotein may be prevalent in refractory angina as a strong primary risk factor," she added.

"Although there's plenty of evidence that lipoprotein apheresis is efficacious in familial hypercholesterolemia, there's very little randomized controlled data looking at whether it should be used for patients with raised lipoprotein. Certainly there are probably no randomized controlled data assessing the clinical benefit of lipoprotein apheresis on refractory angina," Khan said.

"In patients with refractory angina and raised lipoprotein(a), in the absence of substantially raised LDL cholesterol, apheresis led to statistically significant benefits in myocardial perfusion, carotid atheroma, exercise capacity, angina symptom, and quality of life," she said.

Sanofi and Regeneron Pharmaceuticals sponsored the ESCAPE trial. Moriarty reported grants and personal fees from Regeneron, Sanofi, Amgen, Ionis, and Genzyme; personal fees from Duke, Esperiod, Eliaz Therapeutics, Alexion, Aegerion, Amarin, and Lilly; and grants from Pfizer, Catabasis, Novartis, and Kaneka. Disclosures for the coauthors are listed in the article.

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