Esperion Therapeutics’ lead candidate, bempedoic acid, a novel cholesterol-lowering agent, has made steady progress and could meet an important unmet need; many people with high cholesterol either cannot or do not wish to take a statin, and many cannot afford or do not qualify for the expensive new PCSK9 inhibitors. In early May, more positive Phase III data was released, including a significant 18% reduction in low-density lipoprotein (LDL)-cholesterol on top of maximally tolerated statin therapy in high cardiovascular (CV) risk patients (Esperion press release (a), May 2, 2018). Furthermore, there were no new safety signals reported from the second release of Phase III data. At least not in the text of the company’s press release.
However, a link in the press release took readers to a chart that contained some surprising and concerning data: deaths associated with placebo 2, deaths associated with bempedoic acid…13. These number worked out to mortality rates of 0.3% and 0.9% respectively; not good news for a drug with the overarching aim of preserving and extending life. Subsequently, the share price for Esperion plummeted. This is not a great surprise; nothing scares an investor like a drug that kills people. So, is all hope lost?
Not yet. Esperion published another press release on the same day maintaining their plan for regulatory submissions in the United States and Europe in 2019 (Esperion press release (b), May 2, 2018). Those areas of cyberspace dedicated to pharmaceutical industry news quickly became awash with various new bites regarding the trial results, the deaths, and various futures for Esperion and bempedoic acid. Many were negative, but many were also positive. Posts in favor of the drug put the higher death rate down to chance, highlighting the small overall death rate in the trial (15 people out of more than 2,000). Moreover, news from the company emphasized that the deaths were most likely due to cancer or CV disease, and importantly for Esperion, the CV death rate was lower in the bempedoic acid -treated population than in the placebo group.
Of course, the safety of any medication is a critical factor to consider with respect to regulatory approval. But we also live in an age of knee-jerk reactions and sensationalism. In this case, I think it is best to apply one of the golden rules of clinical trials: results must be reproducible. Therefore, we keenly await the next readout of results for bempedoic acid. My gut feeling is that bempedoic acid will turn out to be a safe and effective new addition to the dyslipidemia armamentarium. Unfortunately, regulators are presented with a double-edged sword. They could delay approval of the drug until CV outcomes trial data confirm the safety of the drug and run the risk of people dying early or suffering a CV event due to missing out on the treatment. Conversely, approve the drug based on just the registrational trials potentially putting patients at an increased risk of death from the drug itself. To me, sitting on the fence for a while longer and wait for more Phase III data before deciding the fate of bempedoic acid make sense.
For DRG’s assessment of the dyslipidemia market, please click here.
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