- Esperion Therapeutics looks to have a clear road to regulators for its experimental cholesterol-lowering pill, announcing on Sunday results from a fifth Phase 3 study that more definitively answer lingering questions on the drug's safety.
- Securing positive data from this fifth trial represented the last clinical hurdle before Esperion could move ahead with an application to the Food and Drug Administration for approval of its therapy, called bempedoic acid. The biotech expects to file in the first quarter of next year.
- Esperion has bet bempedoic acid can fill a niche in the market for cholesterol therapies between generic statins and two injectable PCSK9 inhibitors made by Amgen and Regeneron. Recent cuts to the prices of both PCSK9 drugs add a wrinkle to that plan, which may hinge on how payers respond to Esperion's drug if approved.
Questions on bempedoic acid's safety have stuck with Esperion through 2018.
In May, shares in the biotech nearly halved in value after results from an earlier study showed an imbalance in patient deaths between the treatment and placebo arms of the trial. While none were judged related to study drug, the data point spurred doubts that subsequent clinical readouts weren't able to erase.
Now, with more data in hand, Esperion believes it can answer those questions more definitively and move towards regulatory review of bempedoic acid.
Results from the latest trial, called Study 2, showed serious adverse events to be balanced between drug and placebo. Slightly more deaths were reported in the bempedoic acid arm but, again, no fatal adverse events were linked to Esperion's treatment and cardiovascular deaths were balanced between the two trial groups.
Notably, patients given bempedoic acid in Study 2 were less likely to experienced a major adverse heart event compared to those given placebo.
Major adverse cardiovascular events reported in Study 2
|Bempedoic acid (n=522)||Placebo (n=257)|
SOURCE: Data from company
"There is absolutely a trend there," said Esperion CEO Tim Mayleben in an interview with BioPharma Dive, who described the cardiovascular data as a positive surprise. "The separation between the two [groups] is pretty meaningful even though the numbers are small and this is only a one-year study."
Since the study enrolled only 779 patients, the company didn't calculate the relative percentage risk reduction between trial arms. A larger, ongoing cardiovascular outcomes study will help answer questions on comparative heart benefit more fully, but data won't be available for some years yet.
Esperion aims to position its pill as a treatment for the millions of Americans who still need additional lowering of their cholesterol levels despite taking maximum doses of statin therapies or generic Zetia (ezetimibe).
For some, such as those at very high risk or with a genetic condition that causes extremely elevated levels of LDL, or "bad", cholesterol, PCSK9 inhibitors and their potent LDL-lowering effect make for an attractive option.
Esperion, though, argues that most people don't need to resort to the pricey injectable drugs if a middle option like bempedoic acid can deliver sufficient LDL lowering.
In Study 2, bempedoic acid delivered an additional and statistically significant 17% reduction in LDL levels on top of statin therapy compared to statins alone — roughly matching the results seen in an earlier and larger Study 1.
Esperion has also developed bempedoic acid as a fixed-dose combination with ezetimibe. Results from a separate trial of that pairing showed an even greater LDL-lowering of 32% on top of statins.
If Esperion is successful in winning FDA approval next year, though, it will bring bempedoic acid to a market that's shifted since May.
Both Regeneron and Sanofi's PCSK9 inhibitor Praluent (alirocumab) and Amgen's rival Repatha (evolocumab) arrived on market with list prices above $14,000 annually, making Esperion's pitch for an oral medicine costing below $4,000 a year commercially compelling.
But earlier this year, Regeneron and Sanofi cut a deal with Express Scripts to lower the price of Praluent to between $4,500 and $8,000 a year. And, just this week, Amgen announced plans to drop Repatha's price by 60% to $5,850.
Neither move has changed Esperion's strategy, however.
"The changes in pricing for the PCSK9s, both from Regeneron, Sanofi and Amgen, have reinforced and given us even greater conviction about our pricing strategy and positioning strategy," said Esperion's Mayleben.
Esperion still plans to price both bempedoic acid and the fixed dose combination at a price of about $9 or $10 per day, or less than $4,000 per year.
Esperion's Mayleben, though, doesn't believe the lack of longer-term cardiovascular results will weigh much on bempedoic acid if it reaches market as planned.
"We don't expect that to be an inhibition, if you will, of adoption of bempedoic acid and the bempedoic acid combination with ezetimibe," Mayleben said.