Lilly’s evacetrapib failure the end of the road for CETP?

What goes up… Lilly’s hitherto scorching share price tear over the past six months has just been checked abruptly with the shuttering of evacetrapib, wiping 8% from the group’s share price. And Lilly will not be the only company to suffer. Eva is the third CETP inhibitor to crash and burn, and it is beginning to look like the class is a bust. Merck & Co, developer of one of the few remaining such drugs, is down 2% in early trade.

If there are losers from this situation there are also winners. Esperion, hit hard last month on concerns over trial endpoints, is up 4% as its ACL inhibitor is now appearing more like a decent possibility as a cholesterol lowerer. But the PSCK9s are unlikely to see any new challengers for a while yet.


Like Roche’s dalcetrapib in 2012, it was lack of efficacy that killed evacetrapib (Roche’s dalcetrapib failure not end of the road for CETP, May 8, 2012). Lilly has stopped the 12,000-patient phase III Accelerate trial after its independent data monitoring committee found it unlikely to achieve its primary endpoint.

Lilly is discontinuing the drug for high-risk atherosclerotic cardiovascular disease and will conclude other studies in the programme too, swallowing a fourth-quarter charge to R&D expenses of up to $90m pre-tax, or approximately 5 cents per share after tax. This, however, is a fraction of what eva’s development has cost over the years.

The Accelerate efficacy concerns will alarm the other two main CETP developers. Merck’s anacetrapib is in a phase III study in 31,000 patients, Reveal, which is not expected to read out for another couple of years. Reveal could cost Merck half of a billion dollars to fund to completion, and the company might be feeling a little anxious about that investment right now.

The other figure on the CETP scene is Dezima, whose TA-8995 is in phase II. Amgen bought the company last month but does not appear to have been punished for this decision by the markets – it is up 2% so far today. But TA-8995 has not yet entered the tens of thousands-strong phase III trial that will be necessary for approval, and if it chooses, Amgen can wait and see what comes out of Reveal before deciding whether to press on.

That said, the decision to spend $300m on Dezima rather than buying Esperion will need to be justified somehow (Amgen doesn’t buy Esperion, September 17, 2015).


The hypothesis backing CETP inhibition – that boosting HDL levels and cutting LDL levels translates into prevention of atherosclerotic disease and ultimately heart attacks and strokes – has never been conclusively proven.

It is somewhat concerning that one of Lilly’s other great pipeline hopes also rests on an uncertain thesis. With evacetrapib coming up short the group is all the more reliant on solanezumab, its anti-beta-amyloid antibody in development for Alzheimer’s disease.

To contact the writer of this story email Elizabeth Cairns in London at [email protected] or follow @LizEPVantage on Twitter

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