November 9, 2022
BIOINVEST NEWS: Esperion (ESPR)
R&D Event Emphasizes Likelihood of CLEAR to Unlock NEXLETOL/NEXLIZET Potential in LDL Space – BUY
ESPR held an investor R&D event today and did a very solid job of detailing why the upcoming 14,000 patient global cardiovascular outcomes trial (CVOT), CLEAR, is highly likely to deliver a positive result by reducing major adverse cardio events (MACE) by at least 15%. CLEAR is on schedule to deliver top-line data in January with the full dataset to be presented at the America College of Cardiology (ACC) in March.
Study Design Enhanced From Previous Trials Increases Likelihood Of Success
The following slide helps explain our confidence in CLEAR when compared to recently conducted CVOT’s for PCSK9 drugs, Esperion’s ezetimibe versus Amgen’s Repatha (evolocumab) and Regeneron’s Praluent (alirocumab):
The two primary points of differentiation in CLEAR are the longer length of treatment duration, 3.8 years (BA) compared to 2.2 and 2.8 years. The other is CLEAR has enrolled patients with more severe LDL-C of mg/dl 139 compared to mg/dl of 92 in the two PCSK9 CVOTs. The combination of a longer trial (longer LDL suppression) and higher LDL baseline (i.e., more severe) patients both increase the odds for a greater CV benefit in CLEAR, and potentially an ever larger reduction that either the FOURIER and/or ODYSSEY trials resulted in. The slide also shows other areas in which we expect CLEAR to show meaningful secondary endpoints improvements including; lower CRP, lower weight, reduced A1c in Type 2 diabetics (T2DM), and a reduction in new onset T2DM patients.
KOLs Confident In The Study But Also The Market Potential
The call included two global heart disease scientific experts/key opinion leaders (KOLs) – Professor Peter Libby, MD, from Brigham and Women’s Hospital and Harvard Medical School, and C. Michael Gibson, MS, MD, from Harvard Medical Research Institutes. Both KOLs are vastly experienced in the latest clinical trials and current use of the latest cholesterol drugs under development and on the market. With a potential positive CLEAR read out on the near-term horizon, questions for ESPR and KOLs on the call centered on the major difference a CVOT can have on both payers and subsequent prescription growth. For example, one of the KOLs described how difficult it is to prescribe inclirsan (Novartis’ Leqvio) which does not have a CVOT reduction on its label despite the drug’s efficacy and ease of use (every 6 months). This partially explains the difficulties for NEXLETOL/NEXLIZET to date. One of the other difficulties Esperion’s experienced was launching the new drugs just as COVID started in 20202/2021 and the inability to market in person. That addition of the diabetes endpoints in CLEAR will further differentiate Esperion’s compounds from the current market leaders.
According to the KOLs, positive CLEAR data will allow ESPR to essentially re-launch NEXLETOL/NEXLIZET with the power of a new drug that reduces both LDL and MACE. KOLs on the call said that a 15% MACE reduction would significantly impact visibility and subsequent sales for NEXLETOL/NEXLIZET. They both see a major commercial opportunity to offer millions of CV patients – and potential diabetes sufferers – a new option that not only significantly reduce LDL on top of statins, patients intolerant to statin and very importantly, with the reduction in CRP other diabetic measurements, aid in preventing the onset of diabetes.
Pipeline Moving Ahead Shows Additional Confidence in CLEAR
Esperion management discussed progress with two pipeline compounds. One is an oral PCSK9 inhibitor (the others are IV/SC injections). The other is next generation ATP citrate lyase inhibition (ACLYi) platform that can lead to compounds with broad inflammation market opportunities. Investors’ focus of course is on CLEAR, but management’s ability to spend resources/cash on new compounds to us is yet another sign on their confidence in CLEAR.
First Data, Then Sales, Then Takeout
We remain highly confident that ESPR will deliver strong CLEAR outcomes data and lead to a major inflection in NEXLETOL/NEXLIZET sales. Finally, we believe the positive results will lead to an easy bolt-on acquisition of ESPR by any of a handful of CV pharma players.