Beyond Statins: Providing an Alternative for LDL-C Lowering

April 9, 2014
Tim Mayleben
President and Chief Executive Officer

Brian Orelli’s recent article in BioWorld Insight, “Avoiding the PCSK9 frenzy with alternative drug targets,” highlights how the focus and excitement around the PCSK9 inhibitors reflects the high level of interest for effective alternatives to statins for low-density lipoprotein cholesterol (LDL-C) lowering. While the PCSK9 inhibitors—injectable biologic therapies—have demonstrated compelling efficacy, Orelli’s piece reminds us that hypercholesterolemia does not have a one-size-fits all solution. Physicians and patients want and need alternative therapeutic options “beyond statins.”

With the spotlight on the LDL-C lowering treatment pipeline, the team at Esperion remains focused on continuing to advance our clinical development program to deliver positive results for patients who are intolerant to statins. ETC-1002 is a novel, oral, once-daily small molecule therapy that we like to describe as a “statin for patients who can’t tolerate a statin.” This is an apt description as ETC-1002 has been shown in Phase 2a studies to be effective in lowering both LDL-C and hsCRP, a key marker of inflammation, but without some of the side effects associated with statins.

When speaking with Orelli a few weeks ago for his piece, we discussed ETC-1002’s unique dual mechanism of action and reviewed how it inhibits ATP citrate lyase (ACL) while also activating a complementary enzyme, 5’-adenosine monophosphate-activated protein kinase (AMPK). Interestingly, several big pharmaceutical companies originally investigated ACL as a potential target, but at the time these investigations were largely underfunded and ultimately abandoned due to the overwhelming success of statins. In a published review article (Groot, 2003), researchers wrote that efforts targeting this enzyme were unsuccessful due to chemistry (lack of sufficiently potent molecules), not because of the biology of the target enzyme.

Leveraging more than 100 years of combined experience in this therapeutic area, Esperion researchers were able to overcome these limitations – a fact that speaks volumes to the dedication and expertise of our team – and ACL inhibition is now the cornerstone of the LDL-C lowering effects seen with ETC-1002.

In the “beyond statins” era of the LDL-C lowering world, Esperion is uniquely positioned for success in one of the largest, most competitive therapeutic areas in our industry. We are devoted to the development of ETC-1002, a compound with the potential to add value and treat patients by targeting the area of highest unmet medical need in hypercholesteromia—statin intolerant patients.


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