US biopharma Esperion has secured US Food and Drug Administration (FDA) approval for its cholesterol-lowering drug Nexletol in a big comeback after a safety scare with a phase 3 trial just two years ago.
The US regulator has cleared Nexletol (bempedoic acid) as an add-on to diet and maximum-dose statin therapy for patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH), an inherited form of elevated cholesterol.
All was looking tricky for the programme in 2018 when a late-stage study revealed an increase in deaths with bempedoic acid compared to placebo.
The company said it didn’t believe the drug was responsible for the imbalance, but there was speculation it may have to wait for the results of a large-scale cardiovascular outcomes study – not due to generate results until 2022 – before approval might be possible.
Last year however Esperion reported the results of a 2,230-patient trial in ASCVD and HeFH which showed that the drug significantly lowered “LDL-cholesterol and reduced the inflammation biomarker C-reactive protein” when added to statins, and also reinforced the safety data for the drug.
Nexletol’s approval sets up a launch on 30 March, said Esperion, when it will become the first oral, once-daily, non-statin LDL-cholesterol lowering drug to reach the US market since Merck & Co got approval for Zetia (ezetimibe) in 2002.
Bempedoic acid is described as a first-in-class ATP citrate lyase (ACL) inhibitor that inhibits cholesterol synthesis in the liver.
Esperion hasn’t confirmed the exact cost of the drug, but has said it plans to price it affordably at around $10 out-of-pocket for a three-month course.
It could capture up to a quarter of the cholesterol drug market and set it on course for peak sales in the region of $2bn-$3bn, according to analysts at Jefferies.
The company has also filed bempedoic acid in Europe, as well as a combination pill with ezetimibe, filed with both the FDA and EMA. The FDA is due to deliver a verdict on the combination pill later this month.
It will launch into a cholesterol market that was static for years and remains dominated by statins, but has seen a couple of new entrants – two injectable PCSK9 inhibitors from Amgen and Sanofi/Regeneron – and could see a launch later this year for Novartis’ PCSK9 drug inclisiran.
Inclisiran – a gene-silencing drug – which can be dosed just twice a year after an initial loading period – is expected to mount a strong challenge to Amgen’s Repatha (evolocumab) and Sanofi/Regeneron’s Praluent (alirocumab), which have both failed to live up to initial blockbuster sales predictions.
Despite massive price reductions, the two PCSK9 drugs, which are dosed either monthly or bimonthly, have failed to gather much sales momentum despite data showing they can reduce cardiovascular risk. Nexletol won’t be able to make a similar claim unless its cardiovascular outcomes trial comes out positive in 2022.