By Bill Berkrot and Ransdell Pierson
NEW YORK/CHICAGO, Nov 17 (Reuters) - An experimental Merck & Co heart drug, from a class of medicine with a troubled past, appeared to be safe and had a 'jaw dropping' effect in boosting good cholesterol and lowering bad cholesterol, according to data from a clinical trial.
Merck's anacetrapib increased good HDL levels by a stunning 138 percent after 24 weeks of treatment, and lowered levels of bad LDL cholesterol by 40 percent in patients already taking LDL-lowering statins, researchers said.
'The lipid effects are jaw dropping in both directions,' said Dr. Christopher Cannon, the study's lead investigator from Brigham and Women's Hospital in Boston. He presented the data at the American Heart Association scientific meeting in Chicago on Wednesday.
Researchers found no anacetrapib safety issues during the 18-month study, and patients receiving the drug had fewer serious heart problems than those given a placebo.
Even if development of the medicine continues without a hitch, however, it will likely be at least five years before Merck can begin selling the drug.
The best and biggest-selling current treatments for heart disease are statins, like Pfizer Inc's Lipitor, that cut LDL cholesterol and reduce the risk of heart attack by up to 30 percent. Some doctors also prescribe niacin, a B vitamin that can boost heart-protective HDL 25 percent but is not widely used because it causes uncomfortable facial flushing.
Cannon said the hope now is that more-potent and easier to use HDL raisers, like anacetrapib, will further reduce heart risks, something that must still be proved with a large, multiyear study.
Physicians attending the presentation came away impressed.
'My bet is that anacetrapib will become as important as statin therapy, and might in some patients actually replace statins,' said Dr. Patrick Couture, an internal medicine specialist at Laval University in Quebec City.
Cannon said the Eureka moment for him came when he saw the data showing only eight patients taking anacetrapib needed artery-opening procedures during the 18-month study, compared with 28 in the statin-only group.
'That was the moment for me, when I said, 'This looks like it's real.'
Merck shares closed up 37 cents, or 1.1 percent, at $34.47 on the New York Stock Exchange.
PFIZER FLOP
Anacetrapib belongs to a class of drugs called CETP inhibitors that produced one of the most spectacular clinical failures in pharmaceutical history. A pivotal study of Pfizer's highly touted torcetrapib was stopped in late 2006 after higher death rates were found among those taking the drug, once projected for annual sales in excess of $10 billion.
Based on the data from the anacetrapib trial, called Define, 'we are 94 percent confident that anacetrapib doesn't have the clinical (side) effects of torcetrapib,' Cannon said.
The HDL increase seen with anacetrapib 'is double what torcetrapib does; it's four times what niacin can do if you can push niacin to its full 2-gram dose; and 10 times the effect seen with statins,' Cannon said, comparing anacetrapib with other therapies.
Anacetrapib also cut by 36 percent levels of LP(a), which is believed to be an independent cardiovascular risk factor.
The 1,623-patient, trial was designed to show anacetrapib does not have the unintended effects on blood chemistry and increased blood pressure found in detailed analyses of what went wrong with the Pfizer drug.
Compared with the placebo group, patients receiving anacetrapib in the study showed no difference in electrolytes, aldosterone or blood pressure, and no other safety concerns were seen with the drug, Cannon said.
'This trial was set up so that we would have some more reassurance that the drug was safe before doing a gigantic trial. And that's what we found, that it looks safe so far,' Cannon said.
In the wake of torcetrapib, Merck has long known that to gain approval for anacetrapib, it will have to conduct a large so-called outcomes trial to prove its drug cuts heart attacks and death rather than just impacts cholesterol levels.
Plans for that study were announced on Wednesday. It will include some 30,000 patients at high risk of heart attack or other serious heart problems, and take about four years to complete. Enrollment is expected to begin in the second quarter of 2011, researchers said.
Patients in the Define study all had coronary disease or were at high risk for heart disease. In addition to the statins they were already taking, study subjects received either 100 milligrams of anacetrapib or a placebo once a day.
At the start of the study, patients on average had a baseline HDL of 40 and LDL of 81. Those on anacetrapib on average saw HDL leap to 101 and LDL drop to 45. HDL levels of placebo patients rose only to 46, while LDL fell to 77.
Patients whose LDL dropped below 25 were taken off the drug as a precaution, which was part of the study's design. 'We didn't see any problems, but this gets the LDL down as low as its ever been in any study,' Cannon said.
In addition to seeing significantly fewer artery-clearing procedures, such as angioplasty or bypass surgery, researchers observed a trend toward lower rates of cardiovascular death, heart attack, stroke and hospitalization for unstable angina.
'The trend toward fewer cardiovascular events is encouraging and it validates Merck's move to conduct a large outcomes study,' Leerink Swann analyst Seamus Fernandez said in a research note.
Roche and Japan Tobacco are also forging ahead with development of a CETP inhibitor, called dalcetrapib.
'There is very real uncertainty as to what anacetrapib will do on clinical outcomes,' said Rory Collins, co-director of the clinical trial service unit at the University of Oxford, who will lead the outcomes study program.
'It is incredibly exciting. It could be really the next big thing in cardiovascular disease,' Collins said.
(Reporting by Bill Berkrot and Ransdell Pierson; editing by John Wallace, Gary Hill)
((bill.berkrot@thomsonreuters.com; +1 646 223-6030; Reuters Messaging: bill.berkrot.reuters.com@reuters.net)) Keywords: HEART MERCK/HDL (Multimedia versions of Reuters Top News are now available for: * 3000 Xtra: visit http://topnews.session.rservices.com * BridgeStation: view story .134 For more information on Top News: http://topnews.reuters.com) COPYRIGHT Copyright Thomson Reuters 2010. All rights reserved. The copying, republication or redistribution of Reuters News Content, including by framing or similar means, is expressly prohibited without the prior written consent of Thomson Reuters.
NEW YORK/CHICAGO, Nov 17 (Reuters) - An experimental Merck & Co heart drug, from a class of medicine with a troubled past, appeared to be safe and had a 'jaw dropping' effect in boosting good cholesterol and lowering bad cholesterol, according to data from a clinical trial.
Merck's anacetrapib increased good HDL levels by a stunning 138 percent after 24 weeks of treatment, and lowered levels of bad LDL cholesterol by 40 percent in patients already taking LDL-lowering statins, researchers said.
'The lipid effects are jaw dropping in both directions,' said Dr. Christopher Cannon, the study's lead investigator from Brigham and Women's Hospital in Boston. He presented the data at the American Heart Association scientific meeting in Chicago on Wednesday.
Researchers found no anacetrapib safety issues during the 18-month study, and patients receiving the drug had fewer serious heart problems than those given a placebo.
Even if development of the medicine continues without a hitch, however, it will likely be at least five years before Merck can begin selling the drug.
The best and biggest-selling current treatments for heart disease are statins, like Pfizer Inc's Lipitor, that cut LDL cholesterol and reduce the risk of heart attack by up to 30 percent. Some doctors also prescribe niacin, a B vitamin that can boost heart-protective HDL 25 percent but is not widely used because it causes uncomfortable facial flushing.
Cannon said the hope now is that more-potent and easier to use HDL raisers, like anacetrapib, will further reduce heart risks, something that must still be proved with a large, multiyear study.
Physicians attending the presentation came away impressed.
'My bet is that anacetrapib will become as important as statin therapy, and might in some patients actually replace statins,' said Dr. Patrick Couture, an internal medicine specialist at Laval University in Quebec City.
Cannon said the Eureka moment for him came when he saw the data showing only eight patients taking anacetrapib needed artery-opening procedures during the 18-month study, compared with 28 in the statin-only group.
'That was the moment for me, when I said, 'This looks like it's real.'
Merck shares closed up 37 cents, or 1.1 percent, at $34.47 on the New York Stock Exchange.
PFIZER FLOP
Anacetrapib belongs to a class of drugs called CETP inhibitors that produced one of the most spectacular clinical failures in pharmaceutical history. A pivotal study of Pfizer's highly touted torcetrapib was stopped in late 2006 after higher death rates were found among those taking the drug, once projected for annual sales in excess of $10 billion.
Based on the data from the anacetrapib trial, called Define, 'we are 94 percent confident that anacetrapib doesn't have the clinical (side) effects of torcetrapib,' Cannon said.
The HDL increase seen with anacetrapib 'is double what torcetrapib does; it's four times what niacin can do if you can push niacin to its full 2-gram dose; and 10 times the effect seen with statins,' Cannon said, comparing anacetrapib with other therapies.
Anacetrapib also cut by 36 percent levels of LP(a), which is believed to be an independent cardiovascular risk factor.
The 1,623-patient, trial was designed to show anacetrapib does not have the unintended effects on blood chemistry and increased blood pressure found in detailed analyses of what went wrong with the Pfizer drug.
Compared with the placebo group, patients receiving anacetrapib in the study showed no difference in electrolytes, aldosterone or blood pressure, and no other safety concerns were seen with the drug, Cannon said.
'This trial was set up so that we would have some more reassurance that the drug was safe before doing a gigantic trial. And that's what we found, that it looks safe so far,' Cannon said.
In the wake of torcetrapib, Merck has long known that to gain approval for anacetrapib, it will have to conduct a large so-called outcomes trial to prove its drug cuts heart attacks and death rather than just impacts cholesterol levels.
Plans for that study were announced on Wednesday. It will include some 30,000 patients at high risk of heart attack or other serious heart problems, and take about four years to complete. Enrollment is expected to begin in the second quarter of 2011, researchers said.
Patients in the Define study all had coronary disease or were at high risk for heart disease. In addition to the statins they were already taking, study subjects received either 100 milligrams of anacetrapib or a placebo once a day.
At the start of the study, patients on average had a baseline HDL of 40 and LDL of 81. Those on anacetrapib on average saw HDL leap to 101 and LDL drop to 45. HDL levels of placebo patients rose only to 46, while LDL fell to 77.
Patients whose LDL dropped below 25 were taken off the drug as a precaution, which was part of the study's design. 'We didn't see any problems, but this gets the LDL down as low as its ever been in any study,' Cannon said.
In addition to seeing significantly fewer artery-clearing procedures, such as angioplasty or bypass surgery, researchers observed a trend toward lower rates of cardiovascular death, heart attack, stroke and hospitalization for unstable angina.
'The trend toward fewer cardiovascular events is encouraging and it validates Merck's move to conduct a large outcomes study,' Leerink Swann analyst Seamus Fernandez said in a research note.
Roche and Japan Tobacco are also forging ahead with development of a CETP inhibitor, called dalcetrapib.
'There is very real uncertainty as to what anacetrapib will do on clinical outcomes,' said Rory Collins, co-director of the clinical trial service unit at the University of Oxford, who will lead the outcomes study program.
'It is incredibly exciting. It could be really the next big thing in cardiovascular disease,' Collins said.
(Reporting by Bill Berkrot and Ransdell Pierson; editing by John Wallace, Gary Hill)
((bill.berkrot@thomsonreuters.com; +1 646 223-6030; Reuters Messaging: bill.berkrot.reuters.com@reuters.net)) Keywords: HEART MERCK/HDL (Multimedia versions of Reuters Top News are now available for: * 3000 Xtra: visit http://topnews.session.rservices.com * BridgeStation: view story .134 For more information on Top News: http://topnews.reuters.com) COPYRIGHT Copyright Thomson Reuters 2010. All rights reserved. The copying, republication or redistribution of Reuters News Content, including by framing or similar means, is expressly prohibited without the prior written consent of Thomson Reuters.