|
|
|
|
|
Blogs by Walker Joe Jackson
Pfizer's Warning Signs
2/5/2008 3:59:47 PM
Read Walker Jackson's "Rx Conspiracy Files." The life you save may be your own. It's a thriller. It's entertaining. It's mostly exciting fiction except for some medical facts about the questionable practices between, Pharma, MDs and FDA. It's knowledge that'll help you make smart choices about Rx. Below is one of many frightening occurrences in the world of Rx.
Pharmaceuticals
Pfizer's Warning Signs
Matthew Herper and Robert Langreth 12.08.06, 6:00 AM ET
Even before Pfizer started large-scale trials of its failed heart drug, some scientists thought it might do more harm than good. That could have big implications for other drug firms.At an all-day meeting at a Times Square hotel last Saturday, Pfizer (nyse: PFE - news - people ) gathered 100 top cardiologists and showed them data for the company's panoply of heart drugs. The star: torcetrapib, Pfizer's experimental pill to raise good cholesterol, touted as one of the most important medicines in a generation. The doctors were enthralled.
But at 6:30 p.m., during a cocktail reception, Pfizer Chief Medical Officer Joe Feczko silenced the crowd with the announcement that the company was immediately canceling all trials of the drug because it had sharply boosted the death rate of patients in a 15,000 patient trial. "It went from this positive sense of the future into a wake in a second," says Allen Taylor, chief cardiologist at Walter Reed Army Medical Center.
Top cardiologists across the country were shocked by the news. It turned out that 82 patients on the drug had died, versus only 51 deaths among those on standard treatment, with higher rates of other heart problems including heart attacks and surgeries. On Monday, Pfizer chief executive Jeffrey Kindler went on CNBC and called the deaths "very unexpected and surprising." Pfizer has lost $20 billion in market cap since then.
But some researchers had always doubted torcetrapib, some savagely. Even doctors who tested the drug said it was a big gamble. Years before Pfizer's drug went into large-scale trials, some research suggested that drugs like it might actually do more harm than good. In particular, at least three published studies of people with gene mutations that the drug mimicked found unexpectedly higher rates of heart disease.
By casting doubt on how much scientists really understand about heart problems, Pfizer's catastrophic failure is certain to delay heart drugs at other companies as the Food and Drug Administration demands more testing.
Pfizer says it developed torcetrapib in a stepwise and orderly manner. It is still unclear why the drug, which also had the side effect of raising blood pressure, caused so much harm. Pfizer also says torcetrapib's problems were discovered in a timely manner without exposing undue numbers of patients.
Pfizer also says it proceeded with its research with "the support of some of the most respected cardiovascular experts who believed that the HDL hypothesis had great hope," the company said in a statement. "No one can predict the ultimate outcome of clinical research until all the appropriate trials have been completed, and the results from [the torcetrapib study] were deeply disappointing to us and cardiovascular experts around the world." But a few scientists saw disaster coming.
"I kept saying at meetings that this is going to have the opposite effect as intended and ten years from now people would die from it," says Anne Tybjaerg-Hansen of the University of Copenhagen, a heart geneticist who published one of the studies in 2000. "But nobody believed me."
Cholesterol, the fat that makes up the outer coatings of cells but also lines our arteries and causes heart attacks, is ferried about the body by two different molecules. Bad cholesterol, or LDL (low-density lipoprotein), brings the fat to the arteries. HDL (high-density lipoprotein), or good cholesterol, acts as a molecular dump truck that carries cholesterol away from the arteries, preventing buildup of plaque. Big epidemiology studies indicate that patients with low levels of HDL are more likely to die from heart attacks than patients with high levels of HDL, even if their bad cholesterol is not elevated.
Current cholesterol drugs work by cutting LDL. For years, drugs companies have been interested in developing drugs that might further reduce the heart attack rate by boosting good cholesterol. But there have been few clues about how to do so.
One of the first hints came in 1989 when researchers at Columbia University and elsewhere found a group of Japanese patients with extremely high levels of HDL because of rare mutations in a gene called CETP, effectively lowering levels of this essential protein--cholesterol ester transfer protein, an obscure biochemical that plays a vital role in the body's cholesterol transport scheme. The first study suggested that these patients might be exceptionally long-lived.
So Pfizer scientists began a search for a drug to lower CETP levels--research that led to torcetrapib. But as they were working, doubts were already emerging that blocking CETP would help patients. In 1996, a big study of Japanese-American men in Honolulu found that those with mutations that reduced CETP levels had 50% higher risk of heart attacks even though their HDL (good cholesterol) was elevated. Then in 2000, Tybjaerg-Hansen and her colleagues in Copenhagen published their own studies showing that women, but not men, with lower CETP levels had more heart disease, again, despite elevated HDL levels.
Researcher Yuji Matsuzawa of the Osaka University had also studied patients with defective CETP genes (hence lower levels) in the 1990s and found that these individuals appeared to have more clogged arteries. He came up with a theory to explain the counterintuitive results: blocking CETP produced defective HDL, he argued, so that even though HDL levels were sky-high, this did no good. "CETP inhibitors may not be a good tool for the purpose of atherosclerosis," he and his colleagues wrote in a 2000 paper; such drugs might produce "dysfunctional HDL particles" that would promote clogged arteries. Matsuzawa did not return requests for comment.
Measuring HDL and expecting to prevent heart attacks may be like estimating the efficiency of trash removal by counting garbage trucks; the trucks could be empty.
But other genetic work contradicted these negative results. In particular, a 13,700 patient Dutch study in 2004 that found that low CETP levels were beneficial, suggesting torcetrapib would work. Also, an attempt to repeat the Honolulu study showed neutral to positive effects from low CETP levels.
Cardiologists were also encouraged when Pfizer researchers showed that rabbits treated with CETP-blocking drugs had vastly lower levels of artery plaque. Daniel Rader, a University of Pennsylvania cardiologist who helped study the drug, thought that the evidence that torcetrapib would work was mixed, but felt greatly reassured by the positive rabbit studies. "The rabbit studies were the tiebreaker," he says. Alan Tall, the Columbia University researcher who co-discovered CETP, says genetic studies were “murky” and Pfizer was “thoroughly justified” in going forward with human tests.
By 2003, Pfizer's clinical trials in hundreds of patients quickly showed that the Pfizer drug vastly boosted HDL levels by 60% or more. Pfizer's studies indicated that the HDL the drug produced was indeed functional. But the only way to prove whether the drug prevented heart attacks or caused them was to test it in thousands of people for years. With few other good promising compounds in the pipeline, cardiologists eagerly signed on for the big trial.
Several top American cardiologists were aware all along of the concerns that the Pfizer drug might produce dysfunctional HDL. But they figured that the worst-case scenario was that the drug wouldn't work--not that it actually might hurt people. Says Steven Nissen, chairman of cardiology at the Cleveland Clinic and leader of a torcetrapib study: "I certainly didn't think it would be harmful."
Prediman K. Shah, chief of cardiology at Cedars-Sinai Medical Center, says "it is not a total surprise" that torcetrapib didn't work or that it harmed people. The early genetic studies suggested that it could conceivably harm people, though early studies of the drug, including the rabbit studies, suggested just the opposite.
Shah was already worried that there was no data on whether the drug reduced artery inflammation, another risk factor for the heart, and that the drug boosted blood pressure a little bit.
Roger Illingworth, a professor emeritus at Oregon Health & Science University who helped write the national guidelines for cholesterol-lowering drugs, says the fact that patients in Japan with CETP-lowering mutations still had clogged arteries suggested the drug would not work. He would not have given it to his own patients.
Exactly why the Pfizer drug apparently killed people won't be known for some time, if ever. A big hint might come from a large study run by the Cleveland Clinic's Nissen that is using imaging techniques to measure the plaque content of the arteries of patients who took torcetrapib versus those on standard treatment. The results are being analyzed now and are scheduled to be unveiled next March. Nissen says he fears that worries about torcetrapib could make it difficult to find patients willing to take part in clinical trials for CETP-lowering entrants from Roche or Merck (nyse: MRK - news - people ).
But the impact of the torcetrapib disaster could go far beyond lookalike pills. For Allen Taylor, the Army doctor who saw the mood sink at the Pfizer-sponsored cocktail party, torcetrapib's failure has "huge implications." For other heart drugs that work in new ways, he says, it is impossible to know if they are safe and effective without doing a big trial to judge whether or not it saves lives.
Merck, Taylor notes, is doing a giant trial of a new drug to be given with niacin, an approved HDL raiser. There is even reason to doubt another FDA approved and widely-prescribed drug, ezetimibe--the chemical in the blockbusters Vytorin and Zetia, sold by Merck and Schering-Plough (nyse: SGP - news - people ). These drugs cut LDL in a completely new way, but do not raise HDL substantially and have not been proven over the long term to save lives. Merck and Schering are funding a giant trial to measure the pills' benefits and risks. Says Taylor: "We're not as smart as we think we are."
Post a Comment new!
More Blogs by Walker Joe Jackson
• Thank You - Thursday, June 11, 2009
• Ole Blue Eyes - Monday, May 25, 2009
• Al Hirt -Virtuoso Trumpet Player - Sunday, May 24, 2009
• Brand New World For Me - Saturday, May 23, 2009
• My Books - Monday, May 11, 2009
• Walker Jackson's Books - Monday, May 11, 2009
• Lulu.com - Monday, May 11, 2009
• Thank You! - Saturday, May 09, 2009
• What A Great Place to Hang Out - Friday, May 08, 2009
• PI Harry Walker - Wednesday, May 06, 2009
• How Difficult Is It? - Wednesday, May 06, 2009
• Bio - Wednesday, May 06, 2009
• Federal Reserve - Monday, May 04, 2009
• Critics Reviews - Friday, May 01, 2009
• Freeze - Tuesday, April 28, 2009
• Eat, Drink and Be Merry - Tuesday, April 28, 2009
• Mark Twain - Saturday, April 25, 2009
• Laughter the Best Medicine - Wednesday, April 22, 2009
• Private Dick Hackney McTrite - Wednesday, April 22, 2009
• Private Dick Hackney McTrite - Tuesday, April 21, 2009
• Rx Conspiracy Files Continued - Tuesday, April 21, 2009
• Rose, M Petite -Crit - Monday, April 20, 2009
• Laughter - The best Medicine - Friday, April 10, 2009
• James Joyce - Saturday, March 28, 2009
• What Readres Have Said - Thursday, March 26, 2009
• Bio -Walker Jackson - Thursday, March 19, 2009
• Exercise - The Fountain of Youth - Thursday, March 19, 2009
• Wimbledon Ticket Costs 2009 - Thursday, March 12, 2009
• Rose, Ma Petite - Thursday, March 12, 2009
• February Hits 2150 - Saturday, February 28, 2009
• Walker Jackson Son's WEB Pages - Monday, February 23, 2009
• Speech Written Seven Years Ago - Saturday, February 21, 2009
• Pipity Pop! Pipity Pop! Pipity Pop! - Sunday, February 15, 2009
• Famous Quote - Sunday, February 15, 2009
• The Cold Turkey Patch - Sunday, February 01, 2009
• Excerpt From Private Dick Hackney McTrite - Sunday, February 01, 2009
• To Succeed in Life - Saturday, January 31, 2009
• Is Your Rx Safe - Saturday, January 31, 2009
• Fabulous Wimbledon - Monday, January 19, 2009
• Jackson's Books at Lulu.Com - Saturday, January 03, 2009
• Private Dick Hackney McTrite - Friday, January 02, 2009
• Rx Conspiracy File Continued - Thursday, January 01, 2009
• Hits - Thursday, January 01, 2009
• Mark Twain Quotes - Tuesday, December 09, 2008
• America's Economic Dilemma - Tuesday, December 09, 2008
• The National Debt - Tuesday, November 25, 2008
• The Lard to Hard Story - Thursday, November 13, 2008
• Writers' in the Thousands - Thursday, November 13, 2008
• God has Rescued Me for a Third Time - Monday, November 10, 2008
• Jump if You Love Me - Sunday, November 09, 2008
• Jackson's Been to Wimbledon Seven Times/Will Go 2009 - Wednesday, October 15, 2008
• Value of Homes - Sunday, October 12, 2008
• Hmmmm! - Sunday, October 12, 2008
• Hmmmm! - Sunday, October 12, 2008
• Unethical Pharmar - Thursday, October 09, 2008
• Rx Conspiracy Files - Sunday, October 05, 2008
• Rot in Jail You Sorry Scoundrel - Sunday, October 05, 2008
• Vieux Carrè Pillow Strangler - Wednesday, October 01, 2008
• Don't Shiv a Git Blues - Tuesday, September 30, 2008
• Housing Market Relief - Tuesday, September 30, 2008
• Hits This Month - Tuesday, September 30, 2008
• Consider This My Reason for Frustration - Monday, September 29, 2008
• Settlement of a Class Action suit against Drug Companies. - Wednesday, September 24, 2008
• One Reason Oil Is So Expensive - Tuesday, September 16, 2008
• The Spirit of Halloween - Saturday, September 13, 2008
• Walker Jackson's Books - Friday, September 12, 2008
• Popular Fabulous Wimbledon - Monday, September 08, 2008
• Readers' Reviews - Thursday, August 28, 2008
• Rx Conspiracy Files Continued - Wednesday, August 13, 2008
• The Continuing Saga - Pharma, Med Pros and FDA - Tuesday, August 05, 2008
• Sales - Tuesday, August 05, 2008
• Reader Review - Tuesday, August 05, 2008
• Obama's Trip to Bagram Afghanistan - Thursday, July 31, 2008
• Help Me Become Rich and Famous - Sunday, July 27, 2008
• God's Pharmacy !!! - Saturday, July 26, 2008
• Rose, Ma Petite - Friday, July 25, 2008
• Rx Conspiracy Files - Friday, July 25, 2008
• Ballroom Dancing - Thursday, July 24, 2008
• Images of aN'Awlins Sleuth - Thursday, July 24, 2008
• Music, Music, Music - Tuesday, July 22, 2008
• Vieux Carré - Monday, July 21, 2008
• The Story of My Life - Monday, July 21, 2008
• Ole' Blue Eyes - Thursday, July 17, 2008
• The Cold Turkey Patch - Help to Quit Smoking - Wednesday, July 16, 2008
• Fresh Water Pearls from China - Tuesday, July 15, 2008
• Hits Over the Last Seven Days - Monday, July 14, 2008
• Rose, Ma Patite - Readers' Rave - Sunday, June 29, 2008
• ABC's Lost Their Patriotism - Sunday, June 29, 2008
• Don't Worry Be Happy - Friday, June 27, 2008
• A Hint to the Wise - Thursday, June 12, 2008
• The Bird Feeder - Tuesday, June 10, 2008
• My Short Stories - Monday, June 09, 2008
• Horror Trail - Thursday, June 05, 2008
• The Same Old Best Sellers - Thursday, June 05, 2008
• Readers' Rave - Saturday, May 31, 2008
• World Gasoline Price - Saturday, May 31, 2008
• Irish Humor - All Irish humor isn't funny: mine is - Thursday, May 29, 2008
• Excerpt from BLOOD TRUST - Thursday, May 29, 2008
• Subject: John, Hillary, and Obama - Friday, May 23, 2008
• I'm Considering Becoming An Illegal Immigrant - Thursday, May 22, 2008
• Why I Write - Thursday, May 22, 2008
• Who Said? - Wednesday, May 21, 2008
• Greedy Big Oil - Wednesday, May 21, 2008
• Images of a N'Awlins Sleuth - Thursday, May 15, 2008
• Eliminating Oil Dependancy - Monday, May 12, 2008
• The Not So Indigent Rev Wright - Sunday, May 11, 2008
• Get Fit - The Lard to Hard Story - Thursday, May 01, 2008
• What's it all about Alfie? - Monday, April 28, 2008
• A Fish Tail or is it Tale - Sunday, April 27, 2008
• Pfizer's Warning Signs - Friday, April 25, 2008
• Paragraph From Rx Conspiracy Files Continued - Friday, April 25, 2008
• An American View Point - Friday, April 25, 2008
• Images of a N'Awlins Sleuth - Friday, April 18, 2008
• Rose, Ma Petite - Thursday, April 17, 2008
• Harry Who? - Thursday, April 17, 2008
• Thanks AD Members and visitors - Sunday, April 13, 2008
• I believe - Wednesday, April 09, 2008
• Money is Important but It Ain't Going to Make You Happy. - Sunday, April 06, 2008
• Visits to My Posts - Sunday, April 06, 2008
• Why I Write - Friday, April 04, 2008
• Tennis Week - Saturday, March 29, 2008
• A Review of Two of My Books - Friday, March 28, 2008
• Pfizer Email to Me and Others - Cialis - Friday, March 28, 2008
• Greedy Big Oil - Tuesday, March 25, 2008
• Dig This Trivia - Saturday, March 22, 2008
• Walker Jackson Books - Saturday, March 22, 2008
• God - Saturday, March 22, 2008
• Musicians Humor - Saturday, March 22, 2008
• God's Pharmacy - Friday, March 21, 2008
• Cost of Gas - Thursday, March 20, 2008
• My Expanded Bio - Wednesday, March 19, 2008
• Ethanol Vs Crude - Wednesday, March 19, 2008
• The Price of Gas/The Price of Fuel Oil - Wednesday, March 19, 2008
• Let's Show 'Big Oil' That the Consumer is Still Boss - Tuesday, March 18, 2008
• Professional Review of "Vieux Carre Pillow Strangler" - Tuesday, March 18, 2008
• Seventy Seven Going on Sixty Five - Tuesday, March 18, 2008
• A Slice of My Life Embellished - Tuesday, March 18, 2008
• Doctors/ VA HealthCare - Tuesday, March 18, 2008
• Happy St.Pat's Day - Sunday, March 16, 2008
• Rx Chemicals in the Water Supply - Sunday, March 16, 2008
• The National Debt - Friday, March 14, 2008
• Halliburton/VP Cheney - Wednesday, March 12, 2008
• Thank You for Reading My Posts - Tuesday, March 11, 2008
• It Takes Courage to Live. NFM - Tuesday, March 04, 2008
• Your Moneys Worth - Sunday, March 02, 2008
• Uh! Oh! - Sunday, March 02, 2008
• One Hellish Night - Reviews - Sunday, February 24, 2008
• More Rx Cnspiracy Dishonesty - Monday, February 18, 2008
• Dear AD Readers - Monday, February 18, 2008
• Rx Conspiracy Files Continued - Monday, February 18, 2008
• Helloooo! - Monday, February 18, 2008
• I've Had a Wonderful Life - Friday, February 15, 2008
• Book Review By Molly Martin - Friday, February 15, 2008
• Part of a Blog I Read Here - Thursday, February 14, 2008
• Think Outside The Box - Thursday, February 14, 2008
• What's Happened to America? - Wednesday, February 13, 2008
• Starfishes of Phuket Thailand - Monday, February 11, 2008
• Rx Conspiracy Files A Continuing Saga - Sunday, February 10, 2008
• Pity Poor Doctors - Sunday, February 10, 2008
• Helping Other Writers - Thursday, February 07, 2008
• Walker Who? - Wednesday, February 06, 2008
• Pfizer's Warning Signs - Tuesday, February 05, 2008
• 7/11 Flight Patterns - Thursday, January 31, 2008
• Rx Conspiracy File - Thursday, January 24, 2008
• Charterd Plane to Miami - Sunday, January 20, 2008
• Readers' Rave - Friday, January 18, 2008
• Rx Conspiracy Files - Tuesday, January 15, 2008
• Walker Jackson's Magnum Opus - Tuesday, January 15, 2008
• Medical Alert!!! - Saturday, January 12, 2008
• REJECTION - Thursday, January 03, 2008
• When You Critique Another Writer's Work - Friday, November 23, 2007
• Interview With Author Jackson and Dallas Franklin of SWOL - Friday, November 23, 2007
• Helloooo - Tuesday, November 20, 2007
• Deader Than A Coffin Nail - Sunday, November 18, 2007
• An Interview With God - Saturday, November 17, 2007
• The 7 most dangerous lies your doctor's telling you (even if he doesn't know it) - Wednesday, November 07, 2007
• ESBI Charges for Undelivered Services - Wednesday, November 07, 2007
• Interview - Molly Martin and Walker Joe One on One - Tuesday, November 06, 2007
• BLOOD TRUST - Tuesday, November 06, 2007
• Follow the Flight Patterns of 9/11 - Tuesday, November 06, 2007
• Rose, Ma Petite - Tuesday, November 06, 2007
• Private Dick Hackney McTrite - Monday, November 05, 2007
• Tennis Fans Read My Wimbledon Posted at my Home page - Sunday, November 04, 2007
• Private Dick Hackney McTrite-Molly's Reviews - Saturday, November 03, 2007
• Vieux Carre Pillow Strangler-Molly's Review - Saturday, November 03, 2007
• Don't Shiv a Git Blues/A 12-bars Blues - Thursday, November 01, 2007
• Stephen King Said... - Thursday, November 01, 2007
• Helping Other Writers - Sunday, October 28, 2007
• Somebody Scream - Saturday, October 20, 2007
• My Father - Saturday, October 20, 2007
• Private Dick Hackney McTrite - Saturday, October 20, 2007
• Looking For Lyrics to MMO's old records - Monday, October 08, 2007
• Adapt Or Get Out - Friday, October 05, 2007
• Fabulous Wimbledon - Wednesday, October 03, 2007
• Begining of "TWISTS" - Wednesday, October 03, 2007
• The Beginning of "Rx Conspiracy Files" - Wednesday, October 03, 2007
• Wealth/Intelligence - Sunday, September 23, 2007
• You Will be Amazed - Sunday, September 16, 2007
• Government ineptitude - Friday, September 14, 2007
• Class of 1957 - College 50th Anniversary. - Wednesday, September 12, 2007
• Point of View - Monday, September 10, 2007
• Red Beans and Ricely... - Monday, September 10, 2007
• George Who? - Monday, September 10, 2007
• Boot Camp/Guard Duty - Monday, September 10, 2007
• Invitation to Dinner at Antoine's - Sunday, September 09, 2007
• Walker Jackson's Old Man and the Sea - Saturday, September 08, 2007
• Seventy-seven Going on Sixty/Lard to Hard Story - Saturday, September 08, 2007
• Quit Smoking Today/The Cold Turkey Patch - Thursday, September 06, 2007
• Tribute to N'Awlins - Thursday, September 06, 2007
• Phuket, Thailand - Thursday, September 06, 2007
• ENRON - Thursday, September 06, 2007
• Rose, Ma Petite - Wednesday, September 05, 2007
• Why I Write - Wednesday, September 05, 2007
• Rx Conspiracy Files - Wednesday, September 05, 2007
• The Bar-ladies of Phuket Thailand - Wednesday, February 28, 2007
• Phuket Thailand - Sunday, February 04, 2007
• Tennis to be Healthy - Saturday, December 02, 2006
• Hurricane Season - Thursday, June 01, 2006
• The Horseracing Slot Machine - Tuesday, May 23, 2006
• Rose, Ma Petite - Monday, May 22, 2006
• 2006 Graduate - Saturday, May 20, 2006
• Capitalism - Sunday, May 07, 2006
• Skype - Sunday, May 07, 2006
• Fabulous Wimbledon - Tuesday, May 02, 2006
• Incredible - Thursday, April 27, 2006
• Dialysis and Renal Kidney Failure - Tuesday, April 25, 2006
• Book Hit Since 1/21/06 - Sunday, April 16, 2006
• Amazing - Thursday, April 13, 2006
• The Reason I Write - Tuesday, April 11, 2006
• Yearly Physicals for Seniors - Tuesday, April 11, 2006
• PayPal Scam - Tuesday, April 11, 2006
• The White House Imbecile - Tuesday, April 11, 2006
• Irish Humor - Tuesday, April 04, 2006
• That's Very True - Monday, April 03, 2006
• Book Hits Since 1/21/06 - Saturday, April 01, 2006
• More Stupidity Out of Washington - Saturday, March 25, 2006
• Book Hits since 1/21/06 - Friday, March 24, 2006
• The Marvelous Foods of The Big Easy - Friday, March 24, 2006
• CONRON/ENRON - Wednesday, March 22, 2006
• Private Dick Hackney McTrite - Sunday, March 19, 2006
• Hello! One ring-a-ding! Calling all Cars! 911 - 911- 911 - Monday, February 27, 2006
• It Blogs My Mind - Wednesday, February 22, 2006
• Live - Sunday, February 19, 2006
• Heaven Here on Earth/Taken From My Work: - Thursday, February 16, 2006
• Literary Recognition - Tuesday, February 07, 2006
• Rejection - Tuesday, February 07, 2006
• Blog to 'Big Oil,' Bush and state of the nation, - Sunday, February 05, 2006
• It's Remarkable - Thursday, February 02, 2006
|
|
