FirstWord Lists – Eli Lilly scraps evacetrapib: the key questions and conclusions

What hope for the CETP inhibitor class?

Nearly a decade on from Pfizer ceasing development of torcetrapib, Eli Lilly's evacetrapib becomes the third-high profile product in the CETP inhibitor class to flunk in pivotal stage studies (Roche's dalcetrapib was the other). Merck & Co.'s anacetrapib remains in Phase III trials, but it would be a spectacular success were this product to succeed where the others have failed. The odds appear to have got longer.

Didn't Amgen just acquire a CETP inhibitor?

They did, via the acquisition of Dezima Pharma. An upfront payment of $300 million (with the deal rising in potential value to $1.6 billion) showcases Amgen's acknowledgement of development risk within this drug class; nevertheless one would assume management now faces an interesting internal debate before funding for pivotal-stage studies is signed off (ViewPoints: Amgen hedges its bet in dyslipidaemia with Dezima deal).

The PCSK9 inhibitors should benefit

The CETP inhibitors have been considered an outside bet to disrupt the commercial opportunity for the PCSK9 inhibitor class, particularly as they would offer the oral dosing typically associated with cardiovascular therapies and would likely compete on price. Cardiovascular outcomes data expected in 2017 will likely drive increased uptake of Sanofi and Regeneron Pharmaceuticals' Praluent and Amgen's Repatha, and characterises the PCSK9 class as likely having a steady ramp towards peak sales. Time and lack of competition appears increasingly in favour of these products.

As could Esperion

When Amgen acquired Dezima, many asked 'why didn't it buy Esperion Therapeutics?' Esperion is also developing an oral-administered cholesterol medication – ETC-1002 – which appears to work when added to statin therapy. Crucially, however, as an ACL inhibitor, Esperion's drug works by a different mechanism and could benefit profoundly if termination of Eli Lilly's evacetrapib proves prescient to the death of the CETP inhibitor class.

Question marks around Phase III study design for ETC-1002 remain and Eli Lilly's decision to scrap evacetrapib may suggest that lower LDL reductions (in the magnitude of 30 percent) don't deliver an outcomes benefit, but Big Pharma may be tempted to bite. Esperion, however, just became a little more expensive.

Can Eli Lilly afford any more big bets?

Eli Lilly shareholders will take solace in the fact that the company has been the best performing Big Pharma player in 2015 to date, and scored an impressive clinical win recently with its diabetes treatment Jardiance (Physician Views Poll Results: Expectations for increased Jardiance use rise on strength of full CV data; share gain from other oral agents likely).

Some will argue, however, that persistence with evacetrapib – and the vast sums of investment Eli Lilly has made in the process – is indicative of Big Pharma's tendency to be seduced by high-risk, high-reward assets. Of additional concern for Eli Lilly shareholders, is the presence of a second bet on this scale in the form of its experimental Alzheimer's therapy solanezumab. Lilly's shares were down 8 percent in late trading on Monday.

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