- Eli Lilly's decision to abandon a lead heart drug candidate (a CETP inhibitor designed to raise HDL cholesterol, aka the “good” cholesterol) has implications across the industry and raises skepticism about similar products such as Merck's anacetrapib.
- However, it bodes well for Amgen and Sanofi/Regeneron, which market the PCSK-9 inhibitors—a class that has been proven in clinical trials to dramatically decrease LDL cholesterol and improve cardiovascular (CVD) outcomes. The situation is a bit more complicated for Amgen, however, thanks to the firm's recent purchase of a company for its CETP inhibitor.
- Evacetrapib is not the first CETP inhibitor to be consigned to the development dustbin.
Clinically speaking, there's a strong evidence base to support the idea that using CETP inhibitors to increase HDL-C levels and perhaps lower LDL-C levels moderately, should lead not only to an improved lipid profile, but better cardiovascular outcomes. Perhaps that's why several companies have progressed to phase 3 only to discontinue development in the face of poor CVD outcomes in spite of improved lipid profiles.
For example, ten years ago, Pfizer's torcetrapib was hailed as the next big thing in cholesterol reduction, with strong phase 2 results and the expeactation that patients in large-scale clinical three trials would have fewer strokes and heart attacks. The results, however, revealed that not only did torcetrapib not decrease risk of strokes and heart attacks, but that it increased all-cause mortality. The program was promptly scrapped.
Likewise, Roche had a similar development program for dalcetrapib several years ago, which was also discontinued. And now, Eli Lilly is confronting a similar outcome, which begs the question of whether or not Amgen made the right decision when it bought Desima for $300 million, with the goal of continuing development of its seemingly promising CETP inhibitor.
In the case of both Merck and Amgen, it's too early to know, but Lilly's decision has certainly caused some concern about whether or not it makes sense to continue to pursue development of CETP inhibitors—especially considering the impact that the already approved PSCSK-9 inhibitors are having on the anti-cholesterol market.