Biotech Values

[DewDiligence]

LLY’s Evacetrapib Boosts Good Cholesterol

[Evacetrapib is a CETP inhibitor, i.e. it’s from the same drug class as Roche’s Dalcetrapib, MRK’s Anacetrapib, and PFE’s infamous Torcetrapib.]

http://online.wsj.com/article/SB10001424052970204190504577040163501008348.html

›NOVEMBER 16, 2011
By JENNIFER CORBETT DOOREN

A study involving Eli Lilly & Co.'s experimental drug evacetrapib showed it was able to boost good cholesterol levels while lowering the bad kind.

The study was presented Tuesday at the American Heart Association's annual meeting in Orlando, Fla., and published in the Journal of the American Medical Association. It was funded by Eli Lilly and led by doctors at the Cleveland Clinic.

Evacetrapib is designed to inhibit cholesteryl ester transfer protein, or CETP, which is involved in transferring cholesterol particles from HDL—considered the "good" cholesterol—to LDL, referred to as "bad" cholesterol.

CETP inhibitors are primarily designed to raise good cholesterol levels and could be a new way to prevent cardiovascular problems like heart attacks and strokes. The widely used cholesterol-lowering drugs known as statins target LDL or bad cholesterol.

Merck & Co. and Roche also have CETP drugs in development. Daniel Rader, scientific director of clinical research at the cardiovascular institute of the University of Pennsylvania, said the three CETP inhibitors target the same mechanism but work in different ways.

"This is a very exciting new drug that appears to be safe," he said, referring to the new Lilly drug. Dr. Rader, whose research focuses on HDL cholesterol, was asked to discuss the evacetrapib study on behalf of the American Heart Association.

Having naturally high levels of HDL is associated with lower cardiovascular risks, making HDL another target for drug therapy, doctors said. Still, it isn't clear if raising HDL translates into a reduction of cardiovascular events like heart attacks and strokes [see #msg-63656000]. Other drugs like niacin are used to raise HDL but can be difficult drugs to tolerate for many patients, so researchers are looking for new ways to raise HDL.

Steve Nissen, one of the Cleveland Clinic doctors involved in the evacetrapib study, said larger studies will be needed to show if CETP inhibitors are able to reduce cardiovascular events such as heart attacks and strokes.

David Moller, Eli Lilly vice president of endocrine and cardiovascular research and clinical investigation, said the company is planning larger studies of evacetrapib.

In 2006, Pfizer Inc. ended development of its CETP inhibitor, torcetrapib, after a study showed an increase in deaths and cardiovascular events among patients receiving the drug. The move, in turn, slowed development of the drug class. So far, mid-stage data involving CETP drugs from the other companies haven't shown the same risk.

If the drug class does prove successful, Dr. Nissen and other doctors say it could be as big as statins. Despite the success of statins like Lipitor, Crestor and Zocor, cardiovascular disease is still the leading cause of death among Americans. Doctors and pharmaceutical companies are looking for new kinds of treatments.

The study of evacetrapib involved about 400 patients with elevated LDL levels or low HDL levels. There were 10 groups in the study looking at three doses of evacetrapib alone and in combination with the three most-prescribed statins: Crestor, Lipitor and Zocor. Patients had cholesterol levels measured at the study's start and after 12 weeks.

When given with statins, a 100-milligram dose of evacetrapib was able to increase HDL levels by 78.5% to 88.5%. It also lowered LDL cholesterol by 11.2% to 13.9%.

There was no increase in blood pressure and no increase in levels of aldosterone or cortisol, two hormones that were elevated in the earlier Pfizer torcetrapib trial.

Roche is currently the furthest along in development with larger studies of its CETP inhibitor dalcetrapib well under way. Terence Hurley, a Roche spokesman, said the company hopes to file for regulatory approval in the U.S. in 2013.

Merck started a 30,000-patient study of its drug anaceptrapib last year. The research is expected to be completed in 2017, according to information listed about the study on clinicaltrials.gov.‹