Biotech Values

[DewDiligence]

ABT’s TriCor Does Not Benefit Most Diabetics

[The subject is the ACCORD study, which tested Zocor±TriCor in type-2 diabetics at high risk for cardiovascular events. The study data were released Sunday at ACC concurrently with online publication in NEJM (http://content.nejm.org/cgi/content/full/NEJMoa1001282 ). ABT’s own damage-control PR (http://finance.yahoo.com/news/Abbott-Statement-ACCORD-Lipid-prnews-851660241.html?x=0&.v=1 ) points out that TriCor did show a decent-sized (but not statsig) reduction in MACE among the subset of patients with the highest triglycerides and lowest HDL at baseline—precisely those for whom TriCor/TriLipix is indicated in the FDA label. The ever-vocal Steven Nissen says that TriCor should no longer be used, but the consensus view seems to be that the trial outcome will not materially change prescribing habits for TriCor/TriLipix.]

http://www.reuters.com/article/idCNN1419942020100314

›Sun Mar 14, 2010 4:54pm EDT
By Bill Berkrot and Debra Sherman

ATLANTA, March 14 (Reuters) - Adding a triglyceride-lowering drug to cholesterol-fighting statins provided no additional protection from heart attack, stroke and death from heart disease in patients with Type 2 diabetes, according to data from a large study.

The study run by the National Institutes of Health, dubbed Accord, aimed to see if the dual-drug therapy could reduce cardiovascular events in diabetes patients at particularly high risk of serious heart problems due to additional risk factors, such as obesity and high blood pressure.

All subjects in the 5,518-patient trial took Merck & Co's <MRK.N> cholesterol-reducing Zocor, which is available generically as simvastatin.

One group also received TriCor, an Abbott Laboratories <ABT.N> medicine to lower the blood fat triglycerides and raise good HDL cholesterol. TriCor belongs to a class of drugs called fibrates.

There was an 8 percent risk reduction from the combination therapy compared with the statin plus placebo, but researchers said the result did not approach statistical significance, so the small difference could have been a fluke.

"Although our analysis suggests that certain patients may benefit from combination therapy, this study provides important information that should spare many people with diabetes unneeded therapy with fibrates," said Dr. Henry Ginsberg, the study's lead investigator, who presented the data at the American College of Cardiology scientific meeting in Atlanta.

Analysts have said the study was somewhat stacked against TriCor, as the median baseline triglyceride level of patients in the trial -- about 162 -- is well below the level of about 300 at which the drug would typically be prescribed.

"While not without risk, major changes in prescribing habits post Accord seem unlikely," Cowen and Co analyst Sara Michelmore said in a note prior to release of the data.

Dr Steven Nissen, a prominent cardiologist with the Cleveland Clinic, disagreed with that assessment. "The use of fenofibrates will decline precipitously," he predicted. "It's another troubling example of a drug that was approved that didn't work."

The U.S. Food and Drug Administration on Sunday said the data will undergo close scrutiny.

"The FDA will conduct a thorough review of the primary Accord data as soon as they become available," said agency spokeswoman Karen Riley.

MEN MAY HAVE BENEFITED

TriCor and Abbott's newer follow-up fibrate, TriLipix, had combined sales of $1.34 billion in 2009.

A positive result in this patient population could have greatly expanded use of fibrates such as TriCor and TriLipix.

As expected, TriCor fared better in a subgroup of patients with a higher median triglyceride level of 284 and low HDL. Among those patients -- some 17 percent of participants -- the combination therapy led to about a 30-percent reduction in the risk of the composite goal of heart attack, stroke and cardiovascular death. While the risk reduction in the subgroup was not technically statistically significant, Ginsberg said he believed it to be a genuine benefit.

"I do think this is real and supports standard use of the drug, and possibly some expansion of that use to people whose triglycerides are over 200, rather than over 300," he said.

Researchers also found that men may have benefited from the dual therapy, while women appeared to have more heart problems than those on statins alone. The drug, however, has shown a benefit in women in previous studies.

"The results of Accord were widely expected and not surprising given that two-thirds of patients in the trial would not be treated with fibrates under current guidelines," Eugene Sun, Abbott's vice president for global pharmaceutical development, said in a statement.

"The results support how fibrates are used in treatment today."

The overall result could color perception of a pill awaiting a U.S. approval decision that combines TriLipix with AstraZeneca's <AZN.L> powerful statin Crestor. A strong finding in favor of combination therapy might have raised the profile of that pill to be marketed under the brand name Certriad.

A second prong of the NIH Accord program tested 4,733 patients with Type 2 diabetes and elevated blood pressure. It found that more intensive blood pressure lowering [lowering systolic BP to <130] failed to cut the risk of heart attacks, strokes and cardiovascular death significantly more than the current standard of care [lowering systolic BP to 130 but not lower].

There were 208 cardiovascular events in patients whose systolic blood pressure was reduced to below 120, compared with 237 among patients whose target goal was less than 140 -- results researchers deemed not statistically significant.

Current guidelines recommend that adults with Type 2 diabetes maintain systolic blood pressure -- the top number of a blood pressure reading -- at less than 130.

The risk of stroke alone was significantly cut by about 40 percent in the intensive treatment group, although the total numbers were low -- 36 versus 62 in the standard care group.

Researchers also noted higher incidence of complications in the intensive group, including abnormally high levels of blood potassium, and some measures of kidney function were worse.

"Both of these studies provide evidence that going beyond the standard of care provides no substantive additional benefit in this population of adults with diabetes at especially high risk of cardiovascular events," said Denise Simons-Morton, the NIH's Accord project officer.‹