乌鸦传媒

Familial hypercholesterolemia (FH) patients needed far fewer apheresis treatments -- in many cases none at all -- when taking the PCSK9 inhibitor alirocumab (Praluent), researchers reported in the randomized ESCAPE trial.

Frequency of apheresis fell by 75% compared with placebo from weeks 7 through 18 (P<0.0001) under a protocol that allowed for skipping the dialysis-like treatments if alirocumab achieved the 30% chronic LDL reduction level typically achieved with apheresis.

And 63.4% of alirocumab-treated patients skipped all planned apheresis treatments during the period when they could under the trial protocol, from week 7 to 18, , of the University of Kansas Medical Center in Kansas City, reported online in the European Heart Journal.

Nearly on the drug compared with 14% among the placebo group.

"It's an added ammunition in treating these patients' disease and risk," Moriarty, who runs the largest of the approximately 40 apheresis centers in the U.S., told 乌鸦传媒. He said he's started using PCSK9 inhibitors for all his FH patients and finds mixed success in reaching goal.

The process of manually filtering out lipoproteins from the blood takes hours, costs $50,000 to $75,000 a year -- five times the cost of a PCSK9 inhibitor -- and is invasive, Moriarty noted, albeit necessary for only a small population who do not adequately respond to standard lipid-lowering therapies.

Major cost savings would be expected if apheresis can be stopped, noted , of Pitie-Salpetriere Hospital in Paris, said as a discussant for the trial at the Hot Line session where the findings were presented at the European Society of Cardiology meeting in Rome simultaneous with publication.

However, there would be a high cost for those who need both, he pointed out. Also, LDL apheresis has pleiotropic effects not expected with the PCSK9 inhibitor, such as anti-inflammatory and anti-thrombotic effects as well as pro-rheological effects by decreasing fibrinogen, he noted.

, of the University of North Carolina in Chapel Hill, agreed that the findings will be important for this difficult-to-treat disease, but noted that there are still some questions unanswered.

"Of course, the study did not include outcomes, and these will be very important," he said in an interview. "We also need to understand whether the amount of reduction in LDL cholesterol with PCSK9 inhibitors alone is adequate or whether further therapy with statins may be needed to achieve adequate reduction of LDL in these patients."

The phase 3 ODYSSEY-ESCAPE trial included 62 heterozygous FH patients at 14 centers in the U.S. and Germany getting apheresis weekly or every 2 weeks at baseline.

Participants were randomized to subcutaneous injections of alirocumab (150 mg) or placebo every 2 weeks for 18 weeks atop their regular lipid-lowering medications.

In the first 6 weeks, apheresis treatment stayed at patient's established schedule. After that, treatments were skipped if LDL cholesterol had dropped by 30% or more from baseline.

LDL cholesterol was reduced by approximately 50% from baseline with alirocumab but rose 2% on placebo, such that serum concentrations were consistently lower through the trial with the drug (P<0.0001 at weeks 6 and 18).

The alirocumab group had more treatment-emergent adverse events overall (31% versus 16%) but not more serious events (9.8% versus 9.5%).

While the trial included only alirocumab, the assumption is that PCSK9 inhibitors exercise a class effect, such that evolocumab (Repatha) would reduce apheresis frequency as well, Moriarty suggested.

Comment