PCSK9 inhibitors make a lot of biological sense and there is data to support their use in lowering LDL cholesterol; we just have to figure out if we can afford them.
Speaking ahead of a CSANZ 2018 session on hyperlipidaemia, Professor Len Kritharides said the challenge was finding the people in whom PCSK9 inhibition becomes cost effective.
“We have to calculate how much the LDL is lowered and what the likely return on that LDL lowering is because in the Australian health care system, cost is very important. We have to justify everything we do.”
Professor Kritharides, from Concord Hospital and the University of Sydney, said the FOURIER trial of evolocumab clearly demonstrated its effectiveness.
“The drug works, there’s no doubt about that. It lowers cholesterol really well and is very useful particularly for people who have a cholesterol that is above target and people who may be intolerant of statins.”
Data presented at this year’s ACC meeting on alirocumab was also positive, he said.
“The results are consistent and in the alirocumab study there was a decrease in all cause mortality whereas in the FOURIER study there wasn’t, so the results are very supportive of a benefit in the post coronary syndrome population.”
But clinical effectiveness is one thing; cost effectiveness is another.
“And whether we use the data from FOURIER, or in fact we use all the cholesterol lowering trials showing a nice relationship between LDL lowering and outcome, we have to work out how much it costs to do that.”
“Some recent papers suggest that at current pricing, monoclonal antibodies to PCSK9 are very expensive and that it is hard to make a case of cost effectiveness in the general Australian population.”
“It’s only in the highest risk populations that the government supports the use of PCSK9 inhibitors and that’s in the FH populations.”
Professor Kritharides told the limbic that only about one third to one half of the people on statins reach their target. So there are a lot of people who would potentially benefit from a PCSK9 inhibitor.
“But the problem is when does that sort of intervention become good value for money and can we afford drugs that cost $8,000-10,000 per year? And if we do, who are the people who should receive this drug?”
“There is data from the FOURIER study that suggests that some patients with higher risk benefit more, and so one of the challenges for us in the Australian health care system is to identify the patients who are at the very highest risk and maybe for them we will be able to increase access to PCSK9 inhibitors.”
“There are always economic restrictions on what we do and we have to continually review the data to make sure that we are getting the right medication to the right people who benefit the most.”
Professor Kritharides said there was an expectation that the drugs would become more widely available over time.
“That’s what we expect and that is the history of new therapies generally speaking. They come onto the market, they’re expensive, we try to define their place and what represents good value for money, and then over time we sort that out.”
He added that another agent, which interferes with production of PCSK9 at the molecular level – as opposed to a monoclonal antibody that binds with preformed PCSK9 in the circulation – was also on the horizon.
“Incliseran has been shown in studies to lower the LDL effectively – maybe by 50% or so – not quite as effective as the monoclonal autoantibodies but pretty similar.”
“And the real advantage of these is they seem to have an extremely long-lived effect. In some studies you may need only two injections per year to keep the LDL low. So if that is validated with outcome data, then that’s potentially very affordable and very sustainable because then you will have something that is a lot cheaper than a fortnightly monoclonal antibody injection.”
He added that incliseran might be particularly useful in communities that have trouble getting regular medication or in patients where there are difficulties with compliance and follow-up.