As Wall Street hailed Esperion Therapeutics Inc.'s phase II win with its triplet pill to lower cholesterol, the company moved up by three months the filing target for NDAs related to the program, and CEO Timothy Mayleben said partnering talks continue with "very large, global companies. The primary de-risking events have happened."

Esperion (NASDAQ:ESPR) closed Tuesday at $52.13, up $6.96, or 15.4 percent on word of positive top-line results from the study testing bempedoic acid/ezetimibe combination (bempedoic acid 180 mg, ezetimibe 10 mg) plus atorvastatin 20 mg vs. placebo in patients with hypercholesterolemia. The six-week study met its primary endpoint of greater low-density lipoprotein cholesterol (LDL-C) lowering from baseline of 64 percent (p<0.001) in the bempedoic acid/ezetimibe combination plus atorvastatin group, as compared to placebo. Ninety-five percent of patients receiving treatment achieved greater than or equal to 50 percent LDL-C lowering reduction and 90 percent achieved LDL-C levels of less than 70 mg/dL, the company said.

Esperion expects to submit two NDAs for the bempedoic acid/ezetimibe combination pill and bempedoic acid by the first quarter of 2019, three months earlier than previously estimated.

Also in the trial, the bempedoic acid/ezetimibe combo plus atorvastatin demonstrated a reduction of 48 percent (p<0.001) in high-sensitivity C-reactive protein (hsCRP), a marker of the underlying inflammation associated with cardiovascular disease (CVD).

J.P. Morgan analyst Jessica Fye maintained her "neutral" rating on Esperion's shares. "Without an active control arm, the incremental contribution from bempedoic acid is difficult to tease out, but in general [the latest results] appear consistent with prior data, suggesting the efficacy of [the compound] is somewhat diminished in combo with statins," she said.

"Given [that] bempedoic acid has consistently demonstrated LDL-C lowering of 20 percent-plus on top of statins in prior trials, we continue to see a solid likelihood of clinical success when the phase IIIs read out in mid-2018. However, while we still see some upside in the stock after the 74 percent move following FDA feedback, we see fewer catalysts to drive upside in 2017," Fye wrote in a report.

The analyst was referring to the day in March when U.S. regulators decreed Esperion's LDL-C-lowering roadmap an adequate plan to support approval of the compound, the label for which would include specific language for use as an adjunct to maximally tolerated statin therapy in patients with hypercholesterolemia, specifically those at high CVD risk with atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) who require more LDL-C lowering. A follow-on indication for CVD risk reduction is possible after the CLEAR CV outcomes trial completes in 2022. (See BioWorld Today, March 21, 2017.)

Marianne Andreach, senior vice president of product planning, said that "ultimately, what we're doing here is offering physicians, patients and payers more options and more flexibility [so that] physicians can pursue the therapy that they feel best fit to the needs of the patients in front of them. But I think another key piece of this is not just about the LDL cholesterol-lowering efficacy, but about the safety and tolerability – three complementary mechanisms being used together where all three are safe and well-tolerated."

Quick onset

Mayleben said Esperion is "not in any fixed timeline" with regard to a partner. "We have, from the beginning, said that our interest is in doing the right partnership, so we're not necessarily bound by time," although in 2017, the search is top priority, he said. "By the end of this year, we'll be theoretically two years from a commercial launch, and we want to be starting our pre-commercial launch activities."

The company started its search for a chief commercial officer last quarter "and that's going along well," Mayleben said during a conference call with investors, "and we'd also like to have our commercial partner lined up by the end of this year or early next year" but will insist that the company "get the terms that we need for this program."

In keeping with the blueprint set forth to the FDA, Esperion's ongoing phase III push with bempedoic acid includes four global pivotal studies expected to enroll about 3,400 high CVD risk patients with hypercholesterolemia and ASCVD and/or HeFH, or who are deemed "high-risk primary prevention," on optimized background lipid-modifying therapy and with elevated levels of LDL-C. Such patients include those on maximally tolerated statins and those only able to tolerate less than the lowest approved daily starting dose (i.e., patients who are considered statin intolerant).

Analyst Fye said she expects a global phase III bridging study with the bempedoic acid/ezetimibe combo to start by the end of the year, with top-line data by the end of 2018.

Esperion's Andreach said that "at this point, what we're doing is really exploring what would happen with respect to the combination and atorvastatin 20 mg. The next step is the submission of the NDA for the bempedoic acid/ezetimibe combination as well as bempedoic acid by itself. And this study, for us, really is the first step of the series of trials" to explore further how well the combo functions with statins, specifically focusing to start on the most prescribed of those statins, she said.

CEO Mayleben said another boon to the treatment shown in the latest study is onset of action time. "We first measured LDL-C levels at three weeks, and then again at six weeks. What was striking to the thought leaders was that at three weeks, the full effect of the LDL cholesterol-lowering for all of these patients was seen. Typically, you don't see that happening that often or that quickly with an oral drug." He said it "probably has to do with the complementary nature of these three drugs' mechanisms of action," along with a kind of "pan-genotypic response" that was "very satisfying."