The odds that Merck & Co’s high-stakes cholesterol drug will succeed have dropped dramatically after Eli Lilly and Co said its similar medicine failed to reduce heart attacks and strokes, top U.S. heart doctors said.
Lilly on Monday said it was halting a 12,000-patient study of its drug, evacetrapib, an oral medication. In earlier studies, the treatment cut “bad” LDL cholesterol by 30 to 35 percent and doubled the levels of “good” LDL cholesterol. But the influence on cholesterol levels did not ultimately improve patients’ health, dashing hopes for this approach to treating heart disease.
Merck’s anacetrapib is now the only drug in a novel class known as CETP inhibitors that remains in late-stage trials. Data from a 30,000-patient study is expected by 2017 to show whether it reduces the incidence of heart attack and strokes. Wall Street analysts have estimated the drug could reap eventual annual sales of up to $10 billion, if approved.
But with the outlook dimmed for CETP inhibitors, Wall Street analysts on Monday predicted a boost to a competing class of drugs just approved for the U.S. market that work by sharply lowering LDL cholesterol. Shares in Amgen Inc and Regeneron Pharmaceuticals rose on expectations the Lilly decision removed a competitive threat to sales of their injectable drugs, which block a protein called PCSK9.
“CETP inhibitors as legitimate drug targets are dead as of today,” said Dr. P.K. Shah, director of atherosclerosis research at Cedars-Sinai Heart Center in Los Angeles, referring to Lilly’s setback. “For cardiologists looking for heart protection, these drugs were a dream, but they haven’t come true.”
Dr. Steve Nissen, head of cardiology for the Cleveland Clinic, noted that Lilly’s failure follows the demise of two other high-profile drugs in the same class. Pfizer’s Inc’s torcetrapib was discontinued in 2006 due to safety worries, while Roche Holding AG’s dalcetrapib was terminated in 2012 for lack of benefit.
“In baseball you don’t get four strikes,” he said of prospects for Merck’s candidate. Nissen was chairman of the halted Lilly study, which involved trials at 540 sites in 37 countries.
Merck, in an emailed statement, said it looks forward to better understanding Lilly’s decision to pull the plug on evacetrapib, but remains confident in its own drug’s potential success.
CETP inhibitors block a protein that transfers HDL cholesterol to LDL cholesterol, resulting in higher levels of HDL and lower LDL levels. Statins, by contrast, work by reducing the liver’s production of cholesterol.
Amgen and Regeneron’s treatments work by blocking a protein named PSCK9 whose normal function in the body is to maximize the presence of LDL cholesterol that enters the bloodstream.
However, investors are still waiting for proof that PCSK9 inhibitors actually reduce heart attacks and strokes, and don’t just reduce cholesterol. Data from such an “outcomes” trial for Regeneron’s Praluent are expected by late 2016, while those from Repatha’s trial are due in 2017.
Dr. Allen Taylor, chief of cardiology at MedStar Heart and Vascular Institute in Washington, D.C., said it would be unwise to assume the PCSK9 inhibitors are heart-protective just because they slash LDL levels.
“Until you see the trial results, all bets are off,” he said.
Should Merck’s own outcomes data for anacetrapib prove positive, the pill could be a much preferred method for patients over the injections required for PCSK9 treatments.
Lilly shares closed down 7.8 percent on Monday. Merck slipped 0.5 percent. Regeneron shares jumped 4.5 percent, while its PCSK9 partner, Sanofi SA, rose 1.3 percent in Paris. Amgen shares rose 2.4 percent.
(Reporting by Ransdell Pierson; Editing by Michele Gershberg and Leslie Adler)
Source: Reuters Health