Esperion’s cholesterol drug clears the last big safety hurdle, turning the corner to the FDA — now the big challenge looms

Esperion $ESPR looks set to make the final step in its long journey toward a marketing application at the FDA, with good odds of success next year. But the latest batch of positive safety and efficacy data won’t dispel the persistent questions over its sales strategy.

Tim Mayleben

That’s going to take some hard dollar numbers.

First, the trial data.

The drug arm saw a moderate drop in LDL of 18% with a 19% cut in high-sensitivity C-reactive protein. That fits in well with what we’ve seen before in a string of Esperion studies, with the therapy fitting neatly between the generics that dominate the market and the PCSK9s that have had trouble finding traction, spurring some deep discounting that could spell trouble for Esperion.

It was safety where Esperion faced the steepest challenge, as earlier questions focused on some controversial mortality issues that at least temporarily destabilized the stock. Analysts wanted these 52-week results to get a much better idea of any risks presented by this drug. But as Jefferies’ Michael Yee noted, Esperion’s bempedoic acid came through with a clean bill of health.

In the primary safety analysis for this study, the two concerns appear alleviated here with no major issues: (1) CV deaths were balanced at 0.8% drug vs 0.8% pbo, (2) there were no fatal AEs due to neoplasms/ cancer. Other SAEs and fatal AEs were generally balanced (e.g. SAEs of 20% vs 19% pbo and fatal AEs of 1.1% vs 0.8% pbo), and none of the fatal AEs were determined to be related to study medication. The fatal AEs would be balanced at 0.8% vs 0.8% pbo as well, except for two one-off cases obviously not even related to drug – so we believe the fatal AEs are balanced.

The company is also making much out of a trend toward a benefit on major cardio events, or MACE, but they’ll have to nail down that one with an outcomes study, which will take years to play out, with a readout planned for 2022.

Esperion’s executive team plans to submit their US application in early 2019, with an EMA pitch coming soon after.

That all sounded good to investors, who pushed up Esperion’s share price by 10% in pre-market trading Monday.

Assuming there are no nasty surprises to come in the regulatory process, what can we expect in a marketing showdown between little Esperion and the giants at Regeneron/Sanofi and Amgen which have been slashing their prices on the PCSK9 — breakthroughs that have demonstrated a moderate but significant benefit in cardio risk reduction?

The three big players have been steadily axing away at their original prices after payers essentially blocked access to their drugs to a major population. Esperion CEO Tim Mayleben — who is aiming at a significant portion of the market that doesn’t get what they need from statins and don’t need what they can get from PCSK9s — has told me repeatedly that they still expect to price in under the PCSK9 overlords, but his ability to maintain a price advantage will be at the discretion of the big 3.

Amarin’s recent outcomes data, which wowed everyone on its (separate) industrial-strength fish oil approach with triglycerides, also underscores just how changeable the market has been.

You can also count Ethan Weiss, a cardiologist at UC San Francisco, as one of the skeptical observers. In a Tweet out after the data arrived, he noted:

I see the most likely case as bempedoic acid as being a more $$ ezetimibe. Less likely: unexpected benefit due to inflammation or other effects. Also possible it has no CVOT benefit or studies not powered adequately

The big takeaway, though, is that Esperion appears poised to challenge the majors, setting up a further disruption that payers should be more than happy to see. 

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