Hearts & Minds Blog

Key Insights from March 2018 ACC: CLEAR Outcomes Looking Even CLEARer After ODYSSEY – Updated ICER Cost-Effectiveness Analysis A Win for Patients and for the Bempedoic Acid Franchise

Tim Mayleben

President and Chief Executive Officer

Our Lipid Management Team attended the 67th Annual Scientific Session of the American College of Cardiology (ACC) in Orlando this past weekend.  As is tradition following one of the major cardiology meetings, we want to provide our key insights as they relate to Esperion and our bempedoic acid-based therapies.

The standout this year was the presentation of top-line results from ODYSSEY Outcomes (ODYSSEY), a cardiovascular outcomes trial (CVOT) for the injectable PCSK9i, alirocumab, along with the announcement by the Institute for Clinical and Economic Review (ICER) of an updated cost-effectiveness analysis for the therapy.  The ODYSSEY results, similar to those from FOURIER presented at last year’s ACC, together with the ICER analysis, are critically important for patients as they will impact physician prescribing patterns, treatment guidelines, coverage status and reimbursement by payers.  Most notably, the observed 15% cardiovascular disease (CVD) risk reduction benefit in ODYSSEY was strong enough to yet again validate the LDL-C lowering thesis and add confidence to our regulatory pathway for an LDL-C-lowering indication for bempedoic acid.

On the heels of FOURIER and REVEAL, ODYSSEY is the third CVOT of an LDL-C lowering therapy in the past year to report positive results.  This represents consistent validation that LDL-C lowering results in a cardiovascular disease risk reduction benefit.

For Esperion, results from ODYSSEY reinforce the decisions made by our team in designing our own CVOT for bempedoic acid, known as CLEAR Outcomes:

  • Recall that patients enrolling in CLEAR Outcomes will have higher mean baseline LDL-C levels – estimated to be ~135 mg/dL (compared to 87 mg/dL in ODYSSEY and 92 mg/dL in FOURIER). Based on topline results from ODYSSEY, patients with the highest baseline LDL-C levels (those with a median baseline of 118 mg/dL) experienced the greatest benefit. Our decision to enroll patients with high baseline LDL-C levels is further validated by these results.
  • Patients enrolling in CLEAR Outcomes will also have significantly higher baseline CVD risk since they won’t have had the benefit of taking approved doses of statins over a long period of time. Similarly, patients are likely to have higher baseline hsCRP levels than those seen in other CVOTs.  Therefore, CLEAR Outcomes will be treating an even higher CVD-risk patient population.
  • Further, ODYSSEY once again highlighted that duration of therapy is critically important to demonstrating a CVD risk reduction benefit. CLEAR Outcomes, with an expected mean duration of therapy of almost four years (compared to 2.8 years for ODYSSEY and 2.2 years for FOURIER), is positioned to demonstrate a highly compelling CVD risk reduction benefit at completion.
  • As a result, CLEAR Outcomes has the potential to provide an even more robust CVD risk reduction benefit than that of ODYSSEY and FOURIER based on the Cholesterol Treatment Trialists’ (CTT) analysis. Here’s the math: starting with a mean baseline LDL-C of ~135 mg/dL and lowering LDL-C to ~95 mg/dL (as in the recently completed Study 4) results in an absolute unit lowering of LDL-C of 35 – 40 mg/dL.  When combined with a mean duration of therapy of four years, the CTT analysis indicates that CLEAR Outcomes could match the 15% CVD risk reduction benefit seen with ODYSSEY and FOURIER – and perhaps provide an even greater benefit.

As noted above, in conjunction with the ODYSSEY results ICER announced a new cost-effectiveness assessment for alirocumab – and Sanofi/Regeneron indicated that they plan to work with payers to make net price adjustments for those who are willing to substantially reduce or eliminate prior authorization requirements. These utilization management processes by payers have severely limited access historically (at the time of the ACC meeting, it’s estimated less than 15,000 patients are currently taking alirocumab or evolocumab), and led to significant debate during the meeting about the potential impact on prescribing patterns and patient care.

Here’s our take:

  • We are focused on what’s right for patients and, as we’ve previously noted, patients can’t benefit from therapies they can’t take – whether because the therapies are not affordable or not well-tolerated. The recent announcement to offer alirocumab at a lower price is a clear “win” for very high CVD-risk patients because it may lead to greater access and reduce other affordability-related barriers, though we acknowledge that some co-pay challenges may remain for patients who have coverage through the so-called “high-deductible” health plans.
  • Outside of access challenges, another barrier to these therapies remains since they are self-injected bi-weekly or monthly, while patients also must continue to take once-daily oral statins and/or
  • We remain confident that bempedoic acid and the bempedoic acid/ezetimibe combination pill have the potential to become the therapies of choice for the vast majority of patients (an estimated 9.5 million of the 13 million patients who remain at high cardiovascular risk) who need additional LDL-C lowering despite the use of maximally-tolerated LDL-C lowering therapies, usually statins. With convenient, once-daily oral dosing, complementary LDL-C lowering, and cost-effective pricing, we are confident patients, physicians and payers will all benefit.

Esperion has entered our most transformative time as an organization, marked by the recent announcement of positive results from our first pivotal Phase 3 study (Study 4 or the 048 study) of bempedoic acid. We look forward to continuing to deliver our pivotal Phase 3 results throughout this year.

I continue to be incredibly proud of our team and look forward to updating you on our continued progress in the weeks and months ahead.

Bempedoic Acid Franchise Addresses Most Patients Not at LDL-C Treatment Goal