Positive phase II data for Esperion’s fixed-dose pill of bempedoic acid plus Zetia in combination with statin therapy has increased investor hopes that a big pharma partner will swoop in.
Esperion is already making plans to develop the drug alone, raising $150m yesterday to help fund a 12,600-patient cardiovascular outcomes trial, which should strengthen its hand in negotiations. With the combo showing similar cholesterol-lowering effects as PCSK9 inhibitors, but likely to be much cheaper, Esperion is in a good place to compete – but would still benefit from the sales clout and deep pockets of a major partner.
The chances of hooking a collaborator rose with the findings from the phase II trial of fixed-dose bempedoic acid/Zetia plus atorvastatin, which yielded a powerful reduction in low-density lipoprotein (LDL) cholesterol of 64% over baseline in hypercholesterolaemia patients.
Although this study was relatively small – in 63 patients – it puts the combo on a par with the expensive PCSK9-inhibiting antibodies Repatha and Praluent, and marks an improvement on the 24% reduction achieved with single-agent bempedoic acid in combination with statins.
|Comparing the new wave of cholesterol-lowering agents|
|Amgen||Repatha 140mg every two weeks plus statin||Atherosclerotic cardiovascular disease (ASCVD)||-64%|
|Sanofi/Regeneron||Praluent 150mg every two weeks plus statin||Heterozygous familial hypercholesterolaemia/ASCVD||-58%|
|The Medicines Company||Inclisiran 300mg once per quarter*||ASCVD||-57%|
|Esperion||Bempedoic acid plus statin 120mg daily*||Elevated LDL on stable statin therapy||-17%|
|Esperion||Bempedoic acid plus statin 240mg daily*||Elevated LDL on stable statin therapy||-24%|
|Esperion||Bempedoic acid/Zetia 180mg/10mg FDC plus statin*||Elevated LDL||-64%|
|*Phase II trials.|
Esperion, which previously had been bought by and subsequently spun out from Pfizer, saw its shares rise 15% to a two-year high of $52.13 yesterday.
The latest results appear to validate the company’s approach ahead of key phase III readouts next year from cholesterol-lowering studies with single-agent bempedoic acid and the Zetia combination.
Four ongoing trials are focused on patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolaemia whose LDL cholesterol is not adequately controlled with current lipid-modifying therapies.
Esperion is also planning a pivotal “bridging” study of the Zetia combo, which will enroll around 350 patients and should start in the fourth quarter, with results due by the end of 2018.
If positive, these data should allow filings in cholesterol-lowering indications for both the single agent and the combination by the first quarter of 2019.
The results so far suggest that the combo is better at lowering cholesterol, although obviously this will have to be shown in phase III.
Heart of the matter
The more important readout for Esperion will come from the Clear Outcomes cardiovascular outcomes trial, which has a primary completion date of December 2021.
Outcomes studies have become a necessary expense for heart drug developers, but a positive result is not always enough – witness Amgen’s Repatha, which significantly reduced cardiovascular outcomes in the Fourier trial, but not by as much as had been hoped (ACC – No Repatha of glory, March 17, 2017).
At least if bempedoic acid shows a similar benefit it will have an oral formulation on its side and, presumably, its price. One of the complaints after the Fourier results came in was that Repatha’s added benefit was not enough to justify its high cost.
Interestingly, in July Esperion also announced plans for a non-registrational phase II study of bempedoic acid plus Repatha, which is due to report topline results early next year.
With all of these trials going on Esperion must be burning through cash, raising the question whether $150m will get it to the Clear Outcomes readout. If phase III results are equally positive it could be looking for more funds next year – unless a partner steps in first.
|Study||N||Trial ID||Primary completion|
|Clear Harmony – long-term safety/tolerability, single-agent bempedoic acid||2,230||NCT02666664||May 2018|
|Clear Wisdom – efficacy study in patients not controlled by statins, single-agent bempedoic acid||750||NCT02991118||Jun 2018|
|Clear Serenity – efficacy study in statin-intolerant patients, single-agent bempedoic acid||300||NCT02988115||Jun 2018|
|Clear Tranquility – efficacy study, bempedoic acid + Zetia||225||NCT03001076||Jun 2018|
|Clear Outcomes – cardiovascular outcomes study, single-agent bempedoic acid||12,600||NCT02993406||Dec 2021|
|Phase II study of bempedoic acid + Repatha||130||NCT03193047||Mar 2018|