- A late-stage trial win should help biotech Esperion Therapeutics make a better case for its experimental cholesterol drug's place as a middle option between generic statins and pricey PCSK9 inhibitors, although a larger, ongoing study remains a final test.
- Phase 3 data released Monday showed a pill combining Esperion's bempedoic acid with ezetimibe cut levels of "bad" cholesterol by a third, surpassing the lipid lowering effect of either drug given alone or placebo in patients with atherosclerotic heart disease already treated with high doses of statin.
- The results move Esperion a step closer toward its goal of submitting bempedoic acid for U.S. approval early next year. Safety concerns spurred by an earlier trial, however, will keep investors withholding final judgment until the outcome of the final study is known later this fall.
Esperion believes it can succeed where highly anticipated cholesterol-lowering therapies from Amgen and the team of Sanofi and Regeneron have so far failed.
Those drugs, respectively Repatha (evolocumab) and Praluent (alirocumab), came to market in 2015 with blockbuster sales expectations on the back of their potent effect in reducing LDL cholesterol.
But the two PCSK9 inhibitors proved less popular than their makers imagined, as insurers and physicians opted for cheap statins or generic Zetia (ezetimibe) to treat most patients. Repatha and Praluent both carry prices above $10,000 a year, although subsequent deals with payers have lowered the cost for some.
Esperion's strategy in developing bempedoic acid has been to aim for those patients who need more LDL lowering than statins can offer, but don't necessarily need to spring for the dramatic reductions offered by PCSK9s. And, in contrast to the pricey biologics, Esperion plans to price its drug at less than $4,000 a year if it's approved.
To that end, the biotech has advanced studies of bempedoic acid both as monotherapy and combined with ezetimibe into a once-daily pill. Three of those trials have already read out in favor of bempedoic acid, with Monday's results marking the fourth positive milestone.
Esperion's Phase 3 program for bempedoic acid
|Trial||Drug tested||Patients enrolled||Patient population||Status (Results ITT, if given)|
|Study 1||Bempedoic acid||2,230||ASCVD, add-on to statin||Met primary goal, 18% LDL-C lowering but worrisome safety signal|
|Study 2||Bempedoic acid||779||ASCVD, add-on to statin||Data readout delayed to October|
|Study 053||Bempedoic acid + ezetimibe (FDC)||382||ASCVD, add-on to statin||Met primary goal, 32% LDL-C lowering|
|Study 3||Bempedoic acid||345||ASCVD, considered statin intolerant||Met primary goal, 23% LDL-C lowering|
|Study 4||Bempedoic acid||269||ASCVD, considered statin intolerant||Met primary goal, 28% LDL-C lowering|
FDC = fixed-dose combination, ITT = intent-to-treat SOURCE: Company statements
As a fixed-dose combination, bempedoic acid lowered LDL cholesterol by 32% among all patients Esperion intended to treat. (The LDL-C reduction came to 35% when only patients still on treatment were counted.)
In a post-hoc analysis of patients considered statin intolerant, the combo delivered an even higher 43% cut to bad cholesterol — a finding Esperion CEO Tim Mayleben believes could boost bempedoic acid's commercial range.
"What doesn't exist in the treatment landscape today — and why we think that fixed dose combination is absolutely going to be a blockbuster therapy — is because there are patients who can't or won't take statins," Mayleben said in an interview, noting that that group numbers between 3.5 million and 4 million in the U.S.
"For those patients the only therapy that is available to them today is ezetimibe, which gets perhaps up to 20% LDL cholesterol lowering, or an expensive, injectable PCSK9, " he continued. "There is no convenient, oral, once-daily therapy with a non-statin mechanism of action for physicians to prescribe."
While the latest results are a positive sign for bempedoic acid, they won't answer all of investors' questions.
In the longer-running, larger "Study 1," 13 patients in the treatment arm died compared to only 2 in the placebo cohort. Investigators ruled the deaths unrelated to treatment, but the imbalance between arms sparked worries Esperion's drug might not end up being safe.
The resulting stock sell-off cut the company's market capitalization nearly in half, a blow from which it has not yet fully recovered.
Monday's results, though clean on safety, cover only 12 weeks of treatment across just under 400 patients. A more definitive read will come in October, when 52-week results from the fifth — and second-largest — study are due.
Investors seeking clarity on whether Esperion's Goldilocks bet pays off will have to wait a little longer.