Experimental Alzheimer's drug shows early promise

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Posted on 30th July 2008 by Gordon Johnson in Uncategorized

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Date: 7/29/2008 11:44 PM

AP-MED-Alzheimer’s-Drugs/1009

By MARILYNN MARCHIONE
AP Medical Writer

CHICAGO (AP) _ For the first time, an experimental drug shows promise for halting the progression of Alzheimer’s disease by taking a new approach: breaking up the protein tangles that clog victims’ brains.

The encouraging results from the drug called Rember, reported Tuesday at a medical conference in Chicago, electrified a field battered by recent setbacks. The drug was developed by Singapore-based TauRx Therapeutics.

Even if bigger, more rigorous studies show it works, Rember is still several years away from being available, and experts warned against overexuberance. But they were excited.

“These are the first very positive results I’ve seen” for stopping mental decline, said Marcelle Morrison-Bogorad, director of Alzheimer’s research at the National Institute on Aging. “It’s just fantastic.”

The federal agency funded early research into the tangles, which are made of a protein called tau and develop inside nerve cells.

For decades, scientists have focused on a different protein — beta-amyloid, which forms sticky clumps outside of the cells — but have yet to get a workable treatment.

The drug is in the second of three stages of development, and scientists are paying special attention to potential treatments because of the enormity of the illness, which afflicts more than 26 million people worldwide and is mushrooming as the population ages.

The four Alzheimer’s drugs currently available just ease symptoms of the mind-robbing disease.

TauRx’s chief is Claude Wischik, a biologist at the University of Aberdeen in Scotland who long has done key research on tau tangles and studies suggesting that Rember can dissolve them.

He is an “esteemed biologist,” and the research “comes with his credibility attached to it,” said Dr. Sam Gandy of Mount Sinai School of Medicine in New York. He heads the scientific advisory panel of the Alzheimer’s Association.

In the study, 321 patients were given one of three doses of Rember or dummy capsules three times a day. The capsules containing the highest dose had a flaw in formulation that kept them from working, and the lowest dose was too weak to keep the disease from worsening, Wischik said.

However, the middle dose helped, as measured by a widely used score of mental performance.

“The people on placebo lost an average of 7 percent of their brain function over six months whereas those on treatment didn’t decline at all,” he said.

After about a year, the placebo group had continued to decline but those on the mid-level dose of Rember had not. At 19 months, the treated group still had not declined as Alzheimer’s patients have been known to do.

Two types of brain scans were available on about a third of participants, and they show the drug was active in brain areas most affected by tau tangles, Wischik said.

“This is suggestive data,” not proof, Wischik warned. The company is raising money now for another test of the drug to start next year.

The main chemical in Rember is available now in a different formulation in a prescription drug sometimes used since the 1930s for chronic bladder infections — methylene blue. However, it predates the federal Food and Drug Administration and was never fully studied for safety and effectiveness, and not in the form used in the Alzheimer’s study, Wischik and other doctors cautioned.

On Monday at the International Conference on Alzheimer’s Disease, other researchers reported encouraging results from a test of a different experimental drug that also targets tau tangles. That drug, by British Columbia-based Allon Therapeutics Inc., was tested in people with an Alzheimer’s precursor, mild cognitive impairment.

The tau-drug results are in stark contrast to the flop of Flurizan, which was aimed at blocking enzymes that form the beta-amyloid clumps. Myriad Genetics announced in June that it would abandon development of Flurizan after the failure. Full results were presented at the conference Tuesday.

Also, fuller results were given from a closely watched test of bapineuzumab, an experimental drug that aims to enlist the immune system to clear out the sticky brain clumps.

Its developers — New Jersey-based Wyeth and the Irish company Elan Corp. PLC — previously announced that the 240-patient study missed its main goal of improving patients’ mental performance at 18 months.

But the company found a silver lining — the drug appeared to help the roughly 60 percent of people in the study who did not have a gene that scientists think makes Alzheimer’s disease more severe.

The results back up the company’s claims of potential effectiveness in some patients, but now there are concerns about possible side effects. Twelve cases of a type of brain swelling occurred in those on bapineuzumab and none in the placebo group. The swelling caused few if any symptoms, company scientists said, but outside experts said it may have contributed to other side effects.

Those were two or more times more common in patients on bapineuzumab than people given the dummy drug. For example, cases of anxiety occurred in 11 percent versus 4 percent on placebo; paranoia, 7 versus 1 percent. Other complaints were vomiting, high blood pressure, weight loss, and back pain.

Three deaths occurred among the 124 patients given bapineuzumab, but they were not related to the drug, said Dr. Sid Gilman of the University of Michigan, who headed the study’s data safety monitoring board. One death was due to pneumonia and two others to worsening Alzheimer’s disease.

Investors reacted to the news by driving down Wyeth’s shares $5.01, or 11.1 percent, in after-hours trading.

Wyeth and Elan have already said they will move on to late-stage testing of bapineuzumab in more than 4,000 patients.

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On the Net:

National Institute on Aging: http://www.nia.nih.gov

Alzheimer’s Association: http://www.alz.org

Copyright 2008 The Associated Press.

Elan shares fall over Alzheimer's drug results

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Posted on 30th July 2008 by Gordon Johnson in Uncategorized

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Date: 7/30/2008 5:40 AM

By SHAWN POGATCHNIK
Associated Press Writer

DUBLIN, Ireland (AP) _ Shares in Ireland’s major biopharmaceutical company, Elan Corp. PLC, suffered their worst fall in more than three years Wednesday after a drug being developed to fight Alzheimer’s Disease reported disappointing results.

Elan shares plummeted over 27 percent to euro14.90 ($23.25) in morning trade on the Irish Stock Exchange, forcing the wider index into negative territory.

The drop followed Tuesday night’s unveiling of full phase-two results of bapineuzumab. Elan and U.S. biopharmaceutical giant Wyeth have been developing the drug in hopes it could become the first to reverse the brain-ravaging effects of Alzheimer’s, which afflicts more than 25 million people worldwide.

Last month the companies said the drug showed signs of working, but the full trial results indicated that the drug was ineffective in treating people who have the ApoE4 gene most commonly found in Alzheimer’s victims. Among those who lacked the gene, the drug did appear to slow down, if not reverse, mental deterioration.

The detailed findings, presented at the International Conference on Alzheimer’s Disease in Chicago, also linked use of the drug to a wide range of potential side effects, including brain swelling, paranoia, anxiety, vomiting and high blood pressure.

Experts appeared divided on the results, but investors dumped Elan and Wyeth shares because the results were much less upbeat than the companies’ advance characterizations. Elan and Wyeth are already pursuing a final-phase trial involving 4,000 Alzheimer’s victims.

Shares in Wyeth fell more than 7 percent Wednesday on Germany’s DAX index in Frankfurt.

Wyeth is much less dependent on the performance of bapineuzumab than its smaller Irish partner, which is banking on delivering an Alzheimer’s breakthrough for its future growth.

Elan currently is pursuing seven trials of potential drugs for Alzheimer’s and two for multiple sclerosis, an incurable disease that attacks the nervous system.

The Dublin-based company nearly went bankrupt in 2002 following the failure of previous Alzheimer’s research and the discovery of loss-hiding accounting practices, and has battled red ink for the past six years.

But the company said last week it is within a year of returning to profit thanks to the success of Tysabri, an MS drug developed in alliance with U.S. drugmaker Biogen Idec Inc. and approved for sale in the U.S. and European markets in mid-2006.

The last time Elan’s shares fell so sharply was in March 2005, after Tysabri was linked to three cases of a rare, deadly brain disease called PML and was withdrawn suddenly from U.S. sale. The drug returned to the market after extensive screening of Tysabri users found no more PML cases.

Copyright 2008 The Associated Press.

Food industry bit

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Posted on 25th July 2008 by Gordon Johnson in Uncategorized

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Date: 07/25/2008 07:06 AM

By LARRY MARGASAK
Associated Press Writer

WASHINGTON (AP) _ One of the worst outbreaks of foodborne illness in the U.S. is teaching the food industry the truth of the adage, “Be careful what you wish for because you might get it.”

The industry pressured the Bush administration years ago to limit the paperwork companies would have to keep to help U.S. health investigators quickly trace produce that sickens consumers, according to interviews and government reports reviewed by The Associated Press.

The White House also killed a plan to require the industry to maintain electronic tracking records that could be reviewed easily during a crisis to search for an outbreak’s source. Companies complained the proposals were too burdensome and costly, and warned they could disrupt the availability of consumers’ favorite foods.

The apparent but unintended consequences of the lobbying success: a paper record-keeping system that has slowed investigators, with estimated business losses of $250 million. So far, nearly 1,300 people in 43 states, the District of Columbia and Canada have been sickened by salmonella since April.

Investigators initially focused on tomatoes as a culprit. Now they are turning attention to jalapeno peppers.

A former member of Bush’s Cabinet and three former senior officials in the Food and Drug Administration told the AP that government food safety experts did not get the strong record-keeping and trace-back system originally proposed under a bioterrorism law to cope with a major foodborne illness.

“In retrospect, yes, if they (the regulations) had been broader and a bit more far-reaching, it could have helped with this,” said Robert Brackett, senior vice president of the Grocery Manufacturers Association. “It wouldn’t have hurt, for sure.” Brackett formerly was a top safety official at the FDA.

Under pressure in 2003 and 2004, the White House agreed to dilute record-keeping proposals by FDA safety experts.

“If the FDA had been given the resources and authority years ago that it asked for to solve these kinds of problems, I think we would have solved this already,” said William Hubbard, a former FDA associate commissioner.

Tommy Thompson, who was health secretary during the industry’s lobbying campaign, acknowledged that a more robust food-tracking system — opposed by business groups as too expensive — could have helped stem the current illnesses and business losses.

“We went in with the larger package but knew we had to compromise,” Thompson told the AP. “I was satisfied with this being the first step. It’s always better to be a Monday morning quarterback. We could have ended up with nothing. If we had more, would it help the situation now? Yes.”

According to government records reviewed by the AP, business groups met at least 10 times with the White House between March 2003 and March 2004, as the FDA regulations were under debate. Food industry lobbyists successfully blunted proposals using arguments familiar in other regulatory debates: The government’s plans would saddle business with unnecessary and costly regulations.

“The FDA’s strong proposed bioterrorism rules were significantly watered down before they became final,” said Caroline Smith DeWaal, food safety director at the Washington-based Center for Science in the Public Interest. The private advocacy group obtained the White House meeting records under the Freedom of Information Act and provided them to the AP.

Participants in the meetings included companies and trade groups up and down the food chain, including Altria Group Inc. and Kraft Foods Inc., when Altria was Kraft’s parent; The Kroger Co.; Safeway Inc.; ConAgra Foods Inc.; The Procter & Gamble Co.; the American Forest and Paper Association; the Polystyrene Packaging Council; the Glass Packaging Institute; the Cocoa Merchants’ Association of America; the World Shipping Council; and the Food Marketing Institute.

The Grocery Manufacturers Association spent $2.6 million on lobbing in 2003 and 2004, the period when the FDA rules were under consideration, according to federal lobbying records. The Food Marketing Institute spent $1.7 million during the period. The figures were for all lobbying by the trade groups and on their behalf.

The grocery group complained during the comment period that the FDA was overstepping authority that Congress had granted under the new bioterrorism law. It said the FDA wanted a “cradle-to-grave record-keeping system” to track every morsel of food delivered to every retail grocery shelf and said more tracking information does not always produce a better result.

The marketing institute said a proposed tracking system as envisioned by the FDA “would be exorbitantly costly.”

The food industry now says it will agree to a better tracing system operated by the government, as long as the industry can advise how to design it.

“We support the government requiring industry to have traceability systems that are effective and work,” said Jill Hollingsworth, group vice president for food safety programs at the marketing institute. “But industry has to come up with a system that follows products throughout the food chain.”

The FDA official in charge of the current salmonella investigation, David Acheson, said the agency slowly is reviewing paper records to help trace tainted produce. But Acheson disputed arguments that an electronic records system would necessarily have helped investigators.

“We still haven’t managed to figure out this outbreak,” he said in an interview days before the case’s biggest break — discovery of a tainted Mexican-grown jalapeno in a southern Texas warehouse.

The White House Office of Management and Budget defended its meetings with food industry groups in 2003 and 2004, saying it regularly meets with companies and individuals with a stake in proposed government rules.

“Our door is open for anyone — from non-profits, industry representatives to individual citizens — who request meetings on regulations,” OMB spokeswoman Jane Lee said. “These are listening sessions in conjunction with personnel from the regulating agency.”

Copyright 2008 The Associated Press.

Democrats to investigate Ranbaxy allegations

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Posted on 17th July 2008 by Gordon Johnson in Uncategorized

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Date: 07/17/2008 04:52 PM

By MATTHEW PERRONE
AP Business Writer

WASHINGTON (AP) _ A pair of powerful House Democrats will investigate what U.S. regulators knew about allegations that drugmaker Ranbaxy lied about the quality of its products.

Federal prosecutors earlier this week demanded India-based Ranbaxy turn over documents that allegedly show the company fabricated data on its drugs submitted to the Food and Drug Administration.

Reps. John Dingell and Bart Stupak on Thursday questioned whether FDA officials knew about the potentially fraudulent information but approved Ranbaxy’s products anyway. The company markets generic versions of popular medications, including Merck’s blockbuster cholesterol pill Zocor.

“If these allegations are true, Ranbaxy has imperiled the safety of Americans,” Dingell said in a statement. “I would like to know whether FDA officials knew about these allegations and what, if any, action was taken.”

A spokeswoman for the FDA said the agency would not comment on the matter because it is an ongoing investigation.

Last year, FDA employees seized paper and electronic documents from Ranbaxy’s U.S. headquarters in New Jersey.

Ranbaxy’s Chairman Malvinder Mohan Singh on Wednesday vigorously denied the allegations from prosecutors, saying they are part of a conspiracy to undermine the company. He said two rival companies are working to bring down Ranbaxy’s share price, but would not name the parties.

Calls placed to Ranbaxy were not immediately returned Thursday afternoon.

Dingell and Stupak, both of Michigan, have been investigating the FDA’s inspections of foreign drugmakers in the aftermath of safety problems with Baxter International Inc.’s blood thinner heparin.

The drug, which was recalled after being linked to dozens of deaths, contained an ingredient made by a Chinese manufacturer. The FDA said it never inspected the Chinese plant due to a bureaucratic mix-up involving a factory with a similar-sounding name.

Stupak said the Ranbaxy case “may be another example in which FDA found it inconvenient to assure the safety and effectiveness of drugs before approving them.”

Dingell is chairman of the Energy and Commerce Committee, which oversees the FDA, while Stupak chairs its oversight and investigations subcommittee.

Copyright 2008 The Associated Press.

Merck to start Vioxx settlement payouts in August

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Posted on 17th July 2008 by Gordon Johnson in Uncategorized

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Date: 07/17/2008 02:46 PM

By LINDA A. JOHNSON
AP Business Writer

TRENTON, N.J. (AP) _ Merck & Co. will start cutting checks for former users of its withdrawn painkiller Vioxx next month after announcing Thursday that it will fund a $4.85 billion settlement expected to resolve roughly 50,000 lawsuits.

The decision marks the beginning of the end of the four-year legal saga, which began when cardiovascular side effects forced Merck to pull Vioxx off the market in 2004, triggering tens of thousands of lawsuits, sullying its once-spotless reputation and forcing out its then-chief executive.

The Vioxx case has cost Merck at least $6.38 billion, including more than $1.53 billion through March 31 on legal costs for defense research and individual trials, most of which it has won.

Vioxx, which was launched in 1999, brought Merck revenue of $2.5 billion at its peak in 2003and $1.3 billion in 2004. Merck has not been disclosing revenue from prior years.

On Thursday, Whitehouse Station, N.J.-based Merck said more than 97 percent of eligible claimants — 48,550 out of 49,960 — have enrolled in the settlement program, surpassing threshold levels the company required for the deal to proceed. Therefore, Merck said that on Aug. 4 it will waive its right to walk away from the deal reached with plaintiffs’ attorneys last fall.

“I’m just glad that it’s almost over,” said Evelyn Irvin Plunkett of Palm Coast, Fla., who sued Merck in 2003 over the May 2001 heart attack death of her first husband, Richard “Dickie” Irvin. “It’s just been a long, hard fight.”

Plunkett’s family had gone through a mistrial, then lost to Merck at a retrial and won the right to a third trial before being allowed to join in the settlement. She does not know how much she will receive.

Settlement amounts can run from the minimum of $5,000 up to a few million dollars. Payments will be decided by a complicated formula that factors in how serious a claimant’s injury was, how much Vioxx was taken and how many other risk factors the person had.

“Long-term users of Vioxx who had a very severe injury will be well compensated,” said lawyer Andy Birchfield, who served on the plaintiffs’ steering and negotiating committees.

He said the number of plaintiffs participating shows the settlement is a good one.

“This is a great day for the plaintiffs injured by Vioxx who will within weeks begin to receive compensation for their injuries,” said lawyer Chris Seeger, a member of the plaintiffs steering committee coordinating the massive litigation. “I couldn’t be happier for my clients.”

“We’re very pleased to be reaching this milestone because we feel it confirms the program is a good one and a fair one,” said Ted Mayer, Merck’s chief Vioxx lawyer.

Roughly 700 more plaintiffs are considering participating, so Merck has extended the deadline for them to enroll until Oct. 30, he said. About 700 more have not been located by their attorneys.

Former Vioxx users, or their survivors, are eligible for part of the settlement if the patient suffered a heart attack, stroke or death. They must have had pending lawsuits or tolling agreements, which suspend the statute of limitations, as of Nov. 9, 2007, the date the settlement was reached.

To ensure that the settlement ended the bulk of the lawsuits, the company had required participation from at least 85 percent of eligible claimants in four groups: those who had used Vioxx for more than 12 months, had a heart attack, had an ischemic stroke or died.

Merck will put $4.85 billion into the settlement fund over time, with the first $500 million payment scheduled for Aug. 6. The company took a charge for the full $4.85 billion last year.

Eligible claimants who enrolled by March 31 and allege a heart attack or sudden cardiac death could then receive an interim payment, expected to be made by the end of August.

Interim payments to people alleging Vioxx caused an ischemic stroke are to begin in or after February 2009.

Mayer said several thousand additional claimants don’t have injuries eligible for the settlement and have been ordered by judges to produce expert reports supporting their claims.

“We expect to be making motions to dismiss a large number of those claims during the coming weeks and months,” he said.

Merck also faces about 260 potential class-action suits, alleging either harm or financial losses related to Vioxx, that still must be resolved.

Merck withdrew Vioxx from the market on Sept. 30, 2004, after its own research showed the once-blockbuster arthritis pill doubled the risk of heart attack and stroke.

U.S. District Judge Eldon E. Fallon in New Orleans, who has been coordinating much of the litigation, said it’s one of the country’s biggest multidistrict litigation cases — those assigned to one federal judge for pretrial purposes and possible settlement.

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Associated Press writer Janet McConnaughey in New Orleans contributed to this report.

On the Web: http://officialvioxxsettlement.com

Copyright 2008 The Associated Press.