What: Esperion Therapeutics (NASDAQ:ESPR) is down about 40% at 12:20 p.m. EDT after updating investors on the pathway to approval for its cholesterol-lowering drug bempedoic acid, which used to go by the moniker ETC-1002.
So what: The company has always planned on running two types of clinical trials: one to show that bempedoic acid lowers cholesterol, and a second longer study to show that lowering cholesterol results in fewer cardiovascular events -- heart attacks and strokes, for instance. The hope was that the cholesterol-lowering study would be enough for approval, and the cardiovascular outcomes study would simply be added to the label later.
And that's exactly what's happening in Europe. After talking with regulators there, Esperion Therapeutics plans to submit a marketing application showing that bempedoic acid can lower cholesterol by 2019, and then follow it up with an application by 2022 for lowering cardiovascular disease risk.
In the U.S. though, the pathway to approval has been a moving target.
In August 2015, after the end-of-phase 2 meeting with the FDA, management said lowering low density lipoprotein cholesterol (LDL-C) -- that's the bad kind -- would be good enough for approval:
The FDA confirmed that LDL-C remains an acceptable clinical surrogate endpoint for the approval of an LDL-C lowering therapy such as ETC-1002.
By the time the meeting notes arrived a month later, the tone had changed, and management hedged on the possibility that it might actually need an outcomes trial for approval:
FDA has encouraged the Company to initiate a cardiovascular outcomes trial promptly, which would be well under way at the time of the New Drug Application submission and review, since any concern regarding the benefit/risk assessment of ETC-1002 could necessitate a completed cardiovascular outcomes trial before approval.
And then yesterday, Esperion Therapeutics' management threw up their hands and said the FDA has no idea whether cholesterol lowering will be enough when the company completes its trial in 2019:
The Agency indicated its position regarding an LDL-C lowering indication could be impacted by potential future changes in their view of LDL-C lowering as a surrogate endpoint or the possibility of a shift in the future standard-of-care for statin intolerant patients with elevated LDL-C levels.
Now what: The FDA's view on LDL-C lowering might change because Amgen's (NASDAQ:AMGN) Repatha and Praluent, sold by Sanofi (NASDAQ:SNY) and Regeneron Pharmaceuticals (NASDAQ:REGN), are scheduled to release cardiovascular outcome studies in the coming years. If the drugs, which lower cholesterol, don't show improved cardiovascular outcomes, Esperion will have a hard time arguing that bempedoic acid should be approved just because it can lower cholesterol.
Unfortunately, if Amgen, Sanofi, and Regeneron are able to show that their drugs improve cardiovascular outcomes, it could be a "shift in the future standard-of-care" that management cited as one of the FDA's reasons for changing its opinion on lowering cholesterol.
It seems, then, that Esperion and its investors should be hoping that Amgen, Sanofi, and Regeneron are able to show that the drugs lower cardiovascular events, but not by enough to make them so great that the FDA thinks it's risky to have bempedoic acid on the market with its unproven cardiovascular outcomes.
Or they can just wait until 2022.