The cholesterol brawl is heating up again.
A pair of next-generation cholesterol-lowering drugs known as PCSK9 inhibitors came to market in 2015 and have since struggled to gain traction. Now Ann Arbor, MI-based biotech Esperion Therapeutics (NASDAQ: ESPR) thinks it can do with a once-a-day pill called bempedoic acid what the PCSK9 blockers have not: reduce unhealthy cholesterol levels for many people who need help that the current standards of care don’t provide, and do it at a reasonable price.
Esperion is unveiling data today from the first of five clinical trials to produce results between now and September. Based on that body of evidence, Esperion will ask the FDA to approve bempedoic acid in two forms: as a standalone pill, and in a pill combined with a generic cholesterol-lowering treatment called ezetimibe.
In the trial (called Study 4—Esperion isn’t following numerical order), 181 people taking a combination of its bempedoic acid and the generic cholesterol drug ezetimibe, had a mean 23 percent lowering of their so-called “bad” cholesterol, LDL-c, over 12 weeks. The control group of 87 people, who took ezetimibe and a placebo, saw an LDL-c increase of 5 percent.
Esperion also said the bempedoic acid group reported a 32 percent decrease in a blood-borne marker of inflammation associated with higher risk of cardiovascular disease. The placebo group reported a two-percent increase in the marker, known as high-sensitivity C-reactive protein (hsCRP).
Esperion reported no significant safety problems in Study 4.
The data from the study are to be viewed with caution for at least two reasons. First, the study enlisted only 269 patients. It is the smallest of Esperion’s five Phase 3 bempedoic acid studies, which have enrolled nearly 4,000 participants combined.
Second, Study 4 evaluated people who cannot take statins, the most common standard of care, because of side effects. Other studies in Esperion’s program are testing people in the danger zone for cardiovascular events, like heart attacks, who are taking statins but can’t lower their cholesterol enough.
In other words, there’s a long way to go before all the relevant data paint a more comprehensive picture of bempedoic acid’s medical value and its cost-effectiveness. Nonetheless, Esperion CEO Tim Mayleben is taking the unusual step of discussing the drug’s price tag.
Drug companies rarely talk about price until a drug is approved or is coming close. At the earliest, bempedoic acid would be up for approval in 2019. Mayleben confirmed what he first told Bloomberg News in late February: that the once-a-day pill, if approved, would cost $9 or $10, roughly 70 percent less over a full year than the list prices of the next-generation alirocumab (Praluent) and evolocumab (Repatha), twice-a-month injectable drugs that have encountered market resistance.
Alirocumab, from Regeneron Pharmaceuticals (NASDAQ: REGN) and Sanofi (NYSE: SNY), and evolocumab, from Amgen (NASDAQ: AMGN), are part of a drug class called PCSK9 inhibitors. They were hailed as a breakthrough in clinical studies, knocking down cholesterol as much as 70 percent. But their $14,000 annual price tags, even when slashed with discounts, have spurred insurers to block their coverage for many patients. Total sales last year: alirocumab $195 million, evolocumab $319 million. (Pfizer had a PCSK9 inhibitor in Phase 3 but pulled the plug in 2016.)
Partners Regeneron and Sanofi hope the results from a massive long-term study of medical outcomes will change insurers’ minds about alirocumab. The results are due this weekend at an American College of Cardiology meeting.
Amgen had similar hopes for its long-term outcome study of evolocumab. The data came out a year ago. Based on those data, the FDA in December expanded the drug’s prescription label to include prevention of heart attack and stroke. If that update persuades insurers to change their coverage, evolocumab sales could see a boost starting this year.
Mayleben agreed that it’s “odd and unusual” to talk price so early, well before Phase 3 results are ready. But Esperion has “confidence” in the previous round of experimental tests: “The size and scope of our Phase 2 program was unmatched” by other anti-cholesterol drug studies, he said. A spokesman added that Esperion completed nine Phase 2 trials, during which 738 people received bempedoic acid.
Even if the data Esperion reports this morning carry over to Studies 1, 2, and 3, it remains to be seen how receptive insurers, doctors, and patients will be. Esperion is betting its early discussion of price will help frame the debate. “We’re trying to set expectations with payers, patients, and physicians that we’ll be intelligent, open, and have a philosophy of accessibility for our therapies,” Mayleben said.
Still, insurers could wait to see longer-term results—just as they have done with alirocumab and evolocumab—that show how bempedoic acid helps reduce not just cholesterol but heart attacks, strokes, and other cardiovascular events. Esperion is enrolling more than 12,000 people in a long-term study that should wrap up in 2022.