The lipid-lowering market is not what it once was. The advent of generic statins and the rising influence of cost-conscious payers have made it hard for new therapies like the PCSK9 inhibitors to crack the market – especially when armed with data only incrementally better than the standard of care.
Esperion believes that in bempedoic acid it has found a cheap and convenient therapy that could fit between statins and PCSK9s in the treatment continuum. But first it has to prove that the project’s efficacy lives up to expectations. All should soon become clear with pivotal trials starting to yield data in March (see tables below).
|Product||Bempedoic acid +/- ezetimibe|
|% market cap||58%|
|Event||Five phase III trial readouts|
|Date||March 2018 onwards|
Five phase III studies will report this year, and Esperion will want results to be good enough not just for approval, but also to allow it finally to hook a partner. The group has made no bones about the fact it will need help to launch bempedoic acid, with its chief executive, Tim Mayleben, previously telling EP Vantage that any collaborator would have to have a broad commercial infrastructure and geographic footprint.
Cardiovascular companies fitting this bill make up a select group – at the JP Morgan healthcare meeting in January Mr Mayleben said there were “more than five but less than 10” suitable partners, adding that Esperion had had discussions with them all.
He brushed off the idea that would-be collaborators might be awaiting data from bempedoic acid’s cardiovascular outcomes trial, which are not due until 2022. But, in a climate in which a 15% reduction in cardiovascular events was unable to move the needle for Amgen’s Repatha, this is a distinct possibility.
Still, as a small molecule, bempedoic acid should be cheaper and more convenient than Repatha. If Esperion can replicate phase II results suggesting that LDL lowering with a combination of bempedoic acid, ezetimibe and statin therapy was on a par with that seen with the PCSK9s, perhaps the likes of Amgen and Regeneron should start to worry (Positive triplet data spurs Esperion deal-making chatter, August 9, 2017).
Esperion is not giving specific details about bempedoic acid’s price tag, but Mr Mayleben has told EP Vantage that this would be in line with that of pre-generic era statins, which had a list price of $8-10 per day. This would make bempedoic acid significantly cheaper than PCSK9s, which cost around $13,400 per year before discounts.
Interestingly, the company plans to set the same price for the bempedoic acid monotherapy and its fixed-dose combination with ezetimibe, with the chief exec saying the difference in the costs of goods was indistinguishable.
He has stated that both of Esperion’s projects could find a niche, and that they would be used in patients who still have elevated LDL cholesterol despite being on statins and/or ezetimibe; Stifel analysts estimate that this market comprises around 30% of patients on cholesterol therapy, or 13 million people in the US alone.
Among this population, single-agent bempedoic acid might be prescribed to the two thirds of patients who are less than 25% away from their LDL target, and the combo – which so far looks more effective – in more severely affected patients.
Mr Mayleben has also stated that there will still be a place for the PCSK9 inhibitors, but that these will be reserved “for patients who have severe cardiovascular disease, are on a maximum tolerated dose of a statin and need truly dramatic LDL cholesterol lowering”.
Bempedoic acid first has to prove its worth in the five upcoming phase III trials, the first of which, study 4, will read out in March, followed by the much larger “anchor trial”, study 1, in May.
|Upcoming bempedoic acid pivotal trial readouts|
|Trial||Details||N||Primary endpoint||Trial ID||Data due|
|Study 4 (1002-048)||Efficacy in statin-intolerant patients, bempedoic acid + ezetimibe||269||Change in LDL-C at 12 weeks||NCT03001076||Mar 2018|
|Study 1 (1002-040)||Long-term safety in patients on maximally tolerated statins, single-agent bempedoic acid||2,230||Adverse events at one year||NCT02666664||May 2018|
|Study 3 (1002-046)||Efficacy in statin-intolerant patients, single-agent bempedoic acid||345||Change in LDL-C at 12 weeks||NCT02988115||May 2018|
|1002FDC-053||"Bridging" study of bempedoic acid/ezetimibe combo pill||350||Change in LDL-C at 12 weeks||NCT03337308||Aug 2018|
|Study 2 (1002-047)||Efficacy in patients on maximally tolerated statins, single-agent bempedoic acid||779||Change in LDL-C at 12 weeks||NCT02991118||Sep 2018|
|Clear Outcomes||Cardiovascular outcomes study, single-agent bempedoic acid||12,600||Composite of CV adverse events||NCT02993406||2022|
Esperion, which closed a $152m fund raising in August on the back of its phase II combo data, has $274m in cash, which it reckons should fund it well into 2020. If all goes to plan bempedoic acid and the fixed-dose combo should be approved by then.
But to make a real success of its projects the company needs a partner with clout. It had better hope that the phase III data convince.