ESC 2016 – Incremental gains for PCSK9s

In the absence of data showing that the costly new cholesterol-lowering drug Praluent can prevent heart attacks in a broad population, Sanofi and Regeneron are strengthening the case for its use in patients with genetic disease – and they are making that case primarily to payers.

Data presented at the European Society of Cardiology meeting today show that the antibody can reduce the rate of a blood filtering procedure called apheresis by 75% in patients with heterozygous familial hypercholesterolemia and uncontrolled levels of low density lipoprotein (LDL). At $50,000-75,000 a year per patient apheresis is an expensive option, so payers might be keen to initiate treatment with Praluent or the competing drug Repatha on the basis of these data.

Avoiding procedures

Patients with the heterozygous form of hypercholesterolemia receive apheresis if their LDL levels are elevated in spite of statin treatment and they have advancing cardiovascular disease. The procedure involves diverting blood from patients’ arms via an intravenous cannula, passing it through an absorber column to remove LDL and then returning it to the opposite arm.

To lower LDL to healthy levels patients have to undergo this invasive procedure weekly or every other week, and it can take three to four hours. While it can achieve an immediate lowering of 75%, LDL levels rise in between procedures. The Odyssey Escape trial sought to achieve a similar effect through the use of Praluent, an antibody that blocks PCSK9, said chief investigator Patrick Moriarty of the University of Kansas.

All patients continued with scheduled apheresis procedures in the first six weeks of the trial, after which physicians adjusted the schedule based on their LDL response. Between weeks seven and 18, 26 of the 41 patients taking Praluent were able to stop apheresis, seven were able to cut their schedule by more than three quarters, and five by half.

Three of the 21 patients assigned to placebo were able to reduce their scheduled apheresis procedures by more than half, and none by more than three quarters.

Dr Moriarty said the findings had already changed his clinical practice. “I’ve started weaning patients off apheresis and switched them to these drugs,” he said.

He acknowledged that Amgen’s PCSK9 inhibitor Repatha could also be used, saying the benefit was “probably a class effect”.

Cost justified

With sales of the two drugs falling short of early expectations because of their high prices, it will be useful to establish a pharmacoeconomic benefit in this population, small as this may be.

At a US list price for PCSK9 agents of more than $14,000 a year, insurers are reluctant to cover them in anyone but the sickest patients – typically those who have cardiovascular disease and who are unable to achieve healthy LDL levels using statins – or those with genetic disease. Compared with the more than $50,000 a year cost of apheresis, the PCSK9s look like a bargain.

The bigger test of payers’ cost tolerance will be data from the 18,000-patient cardiovascular outcomes trial Odyssey Outcomes, expected next year, and Amgen’s counterpart, the 27,000-patient Fourier trial, which could report later this year. These test the PCSK9 inhibitors in the broader population of high-risk heart disease patients with high LDL levels.

If these can be shown to reduce complications of heart disease, the pressure will be on to use PCSK9s in more patients. Equally, payers will demand to see data showing that their cost can be justified because they avert hospitalisations and invasive procedures.

That could be more difficult to do in the wider population than it was in this smaller apheresis group. But if there is one thing Odyssey Escape showed it was that pharma groups are perhaps more aware than ever that they need to take costs into consideration, even in America’s relatively unstinting healthcare system.

To contact the writer of this story email Jonathan Gardner in Rome at [email protected] or follow @ByJonGardner on Twitter