Results for Merck’s oral cholesterol inhibitor show it to be ‘highly effective’

Finding a PCSK9 inhibitor that can be taken orally has been a tough nut to crack, with all other drugs in the class given by injection. However, results announced at the American Heart Association Scientific Sessions this week suggest that Merck & Co – known as MSD outside the US and Canada – may have succeeded where others have failed.

In a trial involving men and women already taking a statin to control their LDL cholesterol, MK-0616 was shown to decrease levels by about 65% from baseline levels. Another trial of healthy volunteers showed a greater reduction, with LDL cholesterol cut by 90%.

“In spite of how difficult it has been historically to identify and develop oral PCSK9 inhibitors, our goal is to deliver a simple oral medication to help patients lower their bad cholesterol,” said lead study author Douglas Johns, clinical director of translational medicine/clinical pharmacology at Merck.

PCSK9 inhibitors block a liver protein that helps to destroy LDL cholesterol receptors on the surface of cells that take cholesterol out of the bloodstream; more receptors mean more LDL is removed from the blood.

In the first study, 60 healthy male volunteers aged 18 to 50 were randomised, with 37 receiving single oral doses of MK-0616 ranging from 10 to 300mg and 23 receiving a placebo. The 90% drop in LDL cholesterol was seen in all single-dose levels tested.

The second study involved 40 male and female volunteers aged 18 to 65 who had been taking statin medications to control their cholesterol levels for at least three months.

“The initial results are encouraging. However, more clinical studies are needed to confirm these findings, given limited clinical experience with the molecule MK-0616,” said Johns.

Two PCSK9 inhibitors are widely available as injections – Amgen’s Repatha (evolocumab) and Sanofi/Regeneron’s Praluent (alirocumab) – but they have failed to flourish as their manufacturers had hoped. Praluent only saw sales of $45m for Regeneron and $59m for Sanofi in the last quarter while Repatha sold $272m, a huge improvement on the year before due to a significant price cut.

Also, Novartis’ Leqvio (inclisiran) – which has the added convenience of only being injected once every six months – has been approved in Europe but has only just started to be rolled out. The FDA is not expected to rule on the drug until early 2022.

As with all cholesterol-lowering agents, data on improved clinical outcomes – not just reduced blood LDL cholesterol – is vital. Analysts at Evercore ISI have suggested Leqvio could reach peak sales of $2bn, but only if it is shown to reduce cardiovascular disease.