- Esperion Therapeutics investors recoiled on Wednesday after the biotech revealed data from a late-stage pivotal study of its only drug showing there were more patient deaths in the study's treatment arm than its control arm.
- Two patients on placebo died during the clinical investigation versus 13 treated with Esperion's bempedoic acid. Discontinuation due to adverse events was also higher among those receiving the experimental therapy. Esperion said the deaths weren't related to treatment with its drug.
- The Phase 3 study enrolled 2,230 high-risk patients with atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia. Patients given bempedoic acid saw an on-treatment reduction in "bad" cholesterol of 18% versus baseline after 12 weeks, compared to a 2% increase for those given placebo. Percentages of patients who experienced any AEs or serious AEs were essentially the same between the experimental and placebo groups.
Unseating statins has been a particularly difficult exercise for drugmakers in the cholesterol arena. Case in point: PCSK9 inhibitors, which carry strong efficacy profiles but also high price tags that have made them a hard sell to payers. (The price is particularly influential here because, in addition to statins, there are inexpensive lifestyle changes that can lower cholesterol, such as a healthier diet.)
For the products that can break through, there's much to gain. Before generic competition began eating away at its sales in 2017, Merck's cholesterol treatment Zetia (ezetimibe) was raking in more than $2.5 billion annually.
While there haven't been any head to head studies, Esperion's candidate hasn't shown the same amount of efficacy as the PCSK9 drugs on the market. Even so, some analysts are keen on bempedoic acid's potential.
In a May 2 note, Jefferies analyst Michael Yee gave a "Buy" rating on Esperion. He described the fresh safety data as "very clean," adding too that it de-risks the bempedoic acid program and effectively opens the door to a Food and Drug Administration approval, or even M&A activity.
Investors weren't as convinced. Esperion shares tumbled 34% on Wednesday morning, opening at $46.55 apiece.
Study 1 safety results
|% (Number) of Patients|
|Treatment Emergent Adverse Events (AEs)||Bempedoic Acid
|Overview of Aes in All Patients (patient incidence)|
|Any AE(s)||78.5% (1167)||78.7% (584)|
|Serious AE(s)||14.5% (216)||14.0% (104)|
|Discontinuation due to AE(s)||10.9% (162)||7.1% (53)|
|Fatal Adverse Events — Unrelated to Study Treatment||0.9% (13)||0.3% (2)|
SOURCE: Esperion Therapeutics
The best guess for the stock drop would be the fatal adverse events; Yee acknowledged in his note that safety was a key concern among Esperion shareholders.
On a May 2 earnings call, the biotech's head of clinical development Bill Sasiela pointed to the study's patient population in explaining the death imbalance.
"[G]iven the high risk patient population, this is actually an overall number of events of about what you’d expect," he said, adding that Esperion was comforted by the fact that it didn't look as though its drug was the cause of the deaths.
Sasiela noted that the deaths generally fell into two categories: cardiovascular and respiratory. Of the 15 total patients who died, it was fairly common to see a history of cardiovascular events or a history of smoking.
It's worth noting, however, that those types of patients are often the ones in greatest need of cholesterol-lowering medications.
Correction: A previous version of this article mischaracterized the efficacy results for bempedoic acid.