PCSK9 Inhibitors: Weaning FH Patients off Apheresis

Adding a PCSK9 inhibitor to apheresis treatment worked so well in reducing high cholesterol that two-thirds of the patients who got the combination therapy were able to stop apheresis, researchers said today at the European Society of Cardiology's ESC Congress 2016 in Rome, Italy.

The patients had heterozygous familial hypercholesterolemia (FH), a condition in which patients are born with high cholesterol. It puts people who have it at high risk of premature coronary heart disease.

It can come with LDL cholesterol levels that are so high they can be difficult to treat effectively.

Though usual therapies like statins and lifestyle changes can reduce these levels, some patients’ levels will remain too high.

They may be candidates for apheresis, a blood filtering process similar to hemodialysis. That works, but it is relatively new, offered in only four centers in the US, and involves weekly or bimonthly sessions connected to a machine.It is also expensive, costing $50,000 to $75,000 annually and is invasive, and time-consuming.

Invented in 1979, it is offered mostly to FH patients who do not do well on statins, and for them it can be a lifesaver.

Reporting at ESC, researchers said that these patients can be further helped—even weaned off of apheresis—by combining apheresis therapy with injections of a PCSK9 inhibitor, alirocumab (Praluent/Sanofi-Regeneron).

In a study called ODYSSEY-ESCAPE Patrick Moriarity, MD, of the University of Kansas, Kansas City, KS, said he and colleagues found that injections of alirocumab combined with apheresis and other lipid-lowering medications showed these patients “could significantly reduce or even eliminate their need for expensive and time-consuming apheresis treatments.”

The 62 patients were at 14 study sites in the US and Germany. All were receiving apheresis.They were randomized to get the PCSK9 inhibitor or placebo.

By week 18 of the trial, those getting alirocumab had a more than 40% drop in LDL cholesterol. The control group also had a slight drop (3.9%) possibly due to changes in behavior since these patients were in a supervised clinical setting.

Side effects were minimal and similar in both groups.

Significantly, Moriarty said, there was a 75% reduction in the need for apheresis treatment in the subjects who got alirocumab and 63% of patients were able to stop these invasive procedures altogether..

An estimated one person in 200 has FH but only 5% of these people have been diagnosed, Moriarity said in an interview. Though there are now ways to treat FH, the damage caused by high cholesterol is cumulative, the longer people have it, the greater likelihood they will develop heart disease and a shorter life expectancy. That has physicians looking for new ways to treat high cholesterol

When apheresis gained acceptance in the late 1970s, it became popular in other countries, particularly Germany.

Moriarty said he runs one of four apheresis centers in the US, where he currently has 50 patients who receive regular treatment.

“The US has generally lagged behind,” he said.

If the ODYSSEY-ESCAPE results hold up, FH patients who are resistant to statins will have an effective combination therapy in PCSK9 treatment with apheresis.

The drug alone may be enough, Moriarity said, “Almost everyone in the trial had a response of more than 50%.”

“In the future, lipoprotein-apheresis centers may now add alirocumab to a patients lipid-lowering therapy and possibly not have to treat them with apheresis or at least treat them less often,” he said.

The US Food and Drug Administration has approved alirocumab for treatment of heterozygous familial hypocholesteremia.

Cost has been a factor in whether physicians prescribe PCSK9 inhibitors to patients with high cholesterol not related to FH.

Alirocumab treatment can cost about $9,000 a year, but that's a savings over apheresis, Moriarity noted.