Over the past few months Esperion $ESPR has been gradually digging out of the hole it found itself in after a small imbalance of deaths in a recent cholesterol study triggered an alarm for some of the analysts covering the company. And the company’s execs will be keeping their fingers crossed this morning that investors will remain satisfied with their latest set of Phase III data in the buildup to a marketing application and anticipated rollout next year.
But there are no guarantees for this company, which today also signaled that it is bumping back the readout on its big, pivotal safety trial to October, pushing back from a planned showdown next month as August proved a tough month to get all patients in for their final visit.
Esperion’s supporting cast on Wall Street can be expected to nod approvingly as a fixed dose combination of their bempedoic acid with a shot of Zetia hit an added 35% reduction in LDL (on top of statins) for the on-treatment effect at 12 weeks — 32% in the intent-to-treat analysis. That compares to 24% for ezetimibe and 20% for bempedoic acid.
In the ITT analysis that scored 21% for Zetia and 18% for BA. Placebo responses were negligible, allowing for a compelling p value on efficacy (p=0.001).
But what about safety, where all eyes are on any kind of threat?
Where Esperion got into trouble in the spring was a slight imbalance in the rate of death between their drug arm and the placebo group — 13 to 2 — even though none of the deaths were directly linked to the drug and no one changed or halted the study. Statistically, that may have been nothing more than an unlucky drop of the cards — statistically insignificant — but Esperion faces its own unique standards on success that are crafted for each hurdle.
In this latest trial researchers tracked serious adverse events, but they evened out among the therapeutic doses, with 8% in the fixed dose arm, 6% for BA, 9% for Zetia and 2% in the sugar pill arm. But there were no fatalities.
Esperion researchers also tracked a 34% reduction in C-reactive protein for the combo — a key safety biomarker though well short of an outcomes benefit — compared to an increase in the placebo group of 4% and reductions of 20% for BA and 9% for EZE.
“We’re the lipid management experts,” says Esperion CEO Tim Mayleben, who sees his chief task right now as educating the field on what the data indicate. Priced right, Mayleben and his crew believe that they can make their drug the top choice for millions of patients who don’t do well enough on cheap generic statins but also don’t need the full weight of a more expensive PCSK9 drug.
PCSK9 leaders Amgen, Regeneron and Sanofi, though, are doing all they can to undercut that market, squeezing Esperion with lower prices.
Now investors will be waiting until October to find out more about Study 2, which will provide 52-week safety results on a large group of patients. That will set the stage for a marketing pitch on both the monotherapy as well as the combination, Mayleben tells me. The only other study is its big outcomes study in 2022, which Esperion believes won’t be required ahead of a green regulatory light.
That still presents a big hurdle, however.
Payers have set a high bar for cholesterol drugs, leaving Esperion at work trying to thread the needle on efficacy — where PCSK9 drugs can do better — and safety, where any handicap is seen as a potential deal killer with insurers who may well not like the idea of seeing millions of patients gravitate to a pricey new branded drug.
Their see-saw battle for proving efficacious enough to allow the company to shoot for a sweet spot where everyone can be satisfied with a less expensive alternative to PCSK9 will keep the debate alive right up until the company gets a decision on its marketing application. Even after that, the stock could remain a volatile security.
The best place to read Endpoints News? In your inbox.
Comprehensive daily news report for those who discover, develop, and market drugs. Join 37,800+ biopharma pros who read Endpoints News by email every day.Free Subscription