GlaxoSmithKline Plc’s diabetes pill Avandia came under intense scrutiny on both sides of the Atlantic on Friday, leaving the drug’s future uncertain as its maker battles a wave of lawsuits.

In London, the European Medicines Agency (EMA) launched a new review into Avandia’s risks and benefits, adding to pressure on a product that faces a grilling from U.S. experts next week over its cardiovascular safety.

Scientists within the U.S. Food and Drug Administration are deeply divided over Avandia’s heart risks amid conflicting data, according to more than 700 pages of documents prepared for the July 13-14 advisory panel meeting.

The FDA and EMA will consider a range of options, including whether the medicine should be pulled from the market.

Some doctors want to keep Avandia as a possible treatment for lowering blood sugar for people who are not helped by other medicines for diabetes, a disease that causes heart disease, blindness and other complications.

But critics, including some FDA staff, say diabetics have plenty of alternatives and Avandia should be banned.

The pill was once Glaxo’s second-biggest drug but its sales have plunged since safety fears erupted three years ago. Revenues totaled 771 million pounds ($1.17 billion) in 2009, equivalent to 2.7 percent of Glaxo’s group sales.

The big worry for investors, though, is litigation.

Concerns about the medicine’s adverse impact on the heart have triggered a slew of lawsuits in the United States and fresh criticism of the drug from regulators is likely to make matters worse by playing into the hands of plaintiff lawyers.

Glaxo has vigorously defended the medicine, based in part on a study called Record that the British drugmaker said found no higher rates of heart-related hospitalizations or deaths.

An FDA cardiology expert sharply criticized the study in a memo prepared for the advisory panel.

The trial “was inadequately designed and conducted to provide any reassurance about” the cardiovascular risks of Avandia, wrote Dr. Thomas Marciniak, a medical team leader in the FDA division that reviews heart drugs.

But Dr. Ellis Unger, a deputy director in FDA’s drugs center, said “aside from the known risk of heart failure, the study does not appear to demonstrate harm” from Avandia. The drug’s warning label already warns about heart failure risk.

Glaxo’s European medical director, Tony Hoos, said Avandia was “an important treatment option for appropriate Type 2 diabetes patients.”

The company said overall data, including six clinical trials, showed Avandia does not increase the risk of heart attack, stroke or death. The medicine also is the only oral anti-diabetes drug that has been shown to control blood sugar for up to five years, Glaxo said.

The FDA usually follows recommendations from its advisory panels but is not required to.

Glaxo shares closed Friday just 0.2 percent lower on the New York Stock Exchange after closing unchanged in London, where they recovered from being down as much as 2.6 percent.

OUTSPOKEN CRITICS

Persuading doctors and patients of the drug’s benefits is becoming an uphill battle, with two recent negative studies.

In one study, Dr. Steven Nissen, a cardiologist at Ohio’s Cleveland Clinic and an outspoken Avandia critic, offered more ammunition to his 2007 analysis that first suggested Avandia raises heart risks.

In the second, FDA reviewer David Graham found Avandia was more dangerous to the heart than a competitor, Takeda Pharmaceutical Co’s Actos.

Both Graham and Nissen believe the drug is too risky to stay on the market and will speak to the panel.

Ambrian Partners analyst Mike Ward said “the ultimate downside would be a panel recommendation for Avandia’s withdrawal, which FDA would not have to act upon but probably would, given the politics of the situation.”

“More likely, is yet further tightening of Avandia’s label or maybe a restriction on its use to patients failing on Actos therapy,” Ward said.

FDA staff will present results of an analysis comparing Avandia with Actos at next week’s meeting.

A review of several clinical trials found heart attacks, strokes or related deaths were lower for Actos compared with other diabetes drugs or a placebo. FDA staff added, however, that differences in study design limited their ability to directly compare the drugs.

The FDA is turning to the advisory panel to help sort out the mixed data.

“There is not complete unanimity within the FDA about the interpretation of these data,” Dr. Janet Woodcock, head of the FDA’s drugs center, told reporters.

A current trial called Tide was designed to test Avandia directly against Actos. Critics who see Actos as safer have called the study unethical. The FDA will ask the advisory panel if the study should continue.

TEST OF FDA

The Avandia controversy is seen as a test for the FDA under Democratic President Barack Obama and his chosen leader, Commissioner Margaret Hamburg. Doctors, drugmakers, investors and patient advocates are closely watching the decision as a sign of how the agency will handle future medicines.

Concerns have dogged Avandia since 2007 when Cleveland Clinic researchers linked the pill to a higher heart-attack risk. An advisory panel that year agreed the data suggested Avandia may increase the chances of a heart attack for some patients but said the medicine should remain an option.

European regulators have also concluded in a number of previous reviews — the last of which was early this year — that the overall risk-to-benefit balance was favorable.

But that verdict may not last and the EMA said it would decide once relevant data was analyzed if Avandia’s marketing authorization should be revoked, suspended or changed.

Experts from the agency’s Committee for Medicinal Products for Human Use will discuss the issue at their next plenary meeting in London on July 19-22.

Source: Reuters

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GlaxoSmithKline’s diabetes drug Avandia has received a lot of bad press recently. The latest: The FDA may be delaying publication of a new Avandia study underscoring significant risks targeted by previous independent research, Pharmalot reports.  The study compared outcomes among 227,571 Medicare patients taking either Avandia or Takeda’s Actos.  Researchers, including co-author and FDA reviewer David Graham, found that Avandia increased stroke risk by 27 percent, heart failure by 25 percent and death by 13 percent over three years as compared with Actos.

While you’d think the FDA would want to expose such a significant safety issue, Graham’s supervisors haven’t given him permission to release these results for publication–despite repeated requests. Seemingly out of patience, Graham wrote a letter late last month to FDA Commissioner Margaret Hamburg, arguing that it’s critical to get this information out to the public and scientific community as soon as possible.

“JAMA is very interested in our manuscript and we would like to submit it before next Friday, June 4. Gerald Dal Pan, my supervisor is prepared to sign the clearance form (the paper has a disclaimer and does not represent an official FDA position) but won’t unless Dr. Woodcock and Dr. Jenkins approve. He is afraid to act, even though he is the “clearing official,” the letter states (as quoted by Pharmalot).

“My CMS co-authors are also anxious to submit the manuscript and feel that they have a duty to their customers, Medicare patients, to bring these results to public notice in a scientific journal as soon as possible,” the letter adds. “The idea of being blocked from doing this by a sister Agency is a source of concern to them and to me.

Source: FiercePharma

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Johnson & Johnson CEO Bill Weldon will be recuperating instead of testifying next Thursday, when the House Oversight and Government Reform Committee is scheduled to hold a hearing about the recent McNeil recalls.

Weldon had back surgery on Wednesday, according to company spokeswoman Carol Goodrich. J&J will send Worldwide Chairman of the Consumer Group Colleen Goggins to the hearing instead, and Weldon is willing to talk about the recalled products “at a later date,” Reuters reports.

Weldon was the first asked to testify at the May 27 hearing, according to a May 14 release from the committee. FDA Commissioner Margaret Hamburg is also on the invite list.

Committee Chairman Edolphus Towns (D-NY) has said that the hearing will proceed as scheduled. However, ranking member Darrell Issa (R-CA) requested that it be postponed. In addition to Weldon’s absence, the FDA hasn’t completed its inspection of the McNeil facilities, he says. The agency probe was broadened to all of McNeil’s manufacturing operations.

Source: FiercePharma

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We now know a bit more about the problems with children’s medications recalled by Johnson & Johnson: some samples of recalled infant Tylenol contained as much as 24% more of the active ingredient, acetaminophen, as they were supposed to, the WSJ reports.

According to a letter the company sent to physicians and poison-control officials, the medicines in question didn’t hit store shelves and batches on the market tested fine, but that J&J couldn’t guarantee that all bottles “were within specification or that 24% would have been the maximum,” the paper says.

A 24% higher dose wouldn’t likely be medically dangerous, physicians tell the WSJ. Liver damage from acetaminophen would require higher doses, for longer.

Still, it’s concerning to parents who are already worried about the black specks and foreign materials people have complained were floating in some of J&J’s children’s products. Earlier this month FDA head Margaret Hamburg recommended parents use generic versions instead.

And as the WSJ reported earlier, the FDA is expanding its probe of J&J’s McNeil Consumer Healthcare unit, which makes the children’s meds. Congress is also investigating.

Source: The Wall Street Journal

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No, it’s not your paranoid imagination: The FDA really has been cracking down hard on infractions of various kinds. According to BNet Pharma, FDA has issued 186 warning letters so far this year, putting it on track for another big year in enforcement. And there are some movements afoot that could make the agency even more vigilant.

In 2009, FDA dispatched 570 warning letters, more than it had sent in many years. By contrast, it sent out only 436 in 2008 and 381 in 2007. These stats include letters about misleading advertising and missives warning of manufacturing deficiencies.

It’s not as if FDA Commissioner Margaret Hamburg didn’t warn us; she issued something of a manifesto on stepped-up enforcement last year. But government types have been known to vow changes and then fail to follow through. Apparently, that’s not happening on Hamburg’s watch.

And there’s more ahead. Consider the “Bad Ad” program Hamburg unveiled earlier this week. By asking doctors to tattle on misleading promos and other marketing infractions, the agency isn’t just looking for more enforcement tips, but to deter bad actors from the get-go, some industry observers say.

Source: FiercePharma

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Activist group Public Citizen doesn’t want the FDA to wait until its planned July advisory panel meeting on Avandia–it wants an ongoing trial of the controversial drug stopped now.

The group has petitioned the agency to halt the trial, saying that continuing to enroll patients for the 16,000-participant trial puts people with diabetes at an unnecessary risk. ”[The trial] is exposing thousands of high-risk patients with diabetes to a drug with an unfavorable safety profile and no clinical advantage over its comparator,” the group–along with Canadian researcher Dr. David Juurlink–contend in a letter to FDA Commissioner Margaret Hamburg.

FDA officials say there’s no need for immediate action and pledged to listen to its advisory committee’s opinions in July before making any moves on Avandia. It was the agency that asked for the trial in the first place. After cardiovascular-safety concerns arose in 2007, the FDA directed GlaxoSmithKline to test Avandia against rival drug Actos, with an eye to the drug’s long-term effects on heart health.

The agency says it’s already reviewing all the data available on Avandia and hasn’t yet come to any conclusions, Reuters reports. Hence the advisory panel slated for July: ”Based on expert input and our own analysis,” agency spokeswoman Karen Riley tells the news service, “FDA will reassess the rationale for the TIDE trial, review the trial’s enrollment and respond accordingly.”

Source: FierceBiotech

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The Food and Drug Administration on Saturday urged consumers to stop using liquid Tylenol, Motrin, Benadryl and Zyrtec medicines for children and infants after a broad recall announced by the manufacturer, although it said the chance of serious problems was remote.

Johnson & Johnson’s consumer division announced a broad recall of products, including certain liquid infant’s and children’s Tylenol, Motrin, Zyrtec, and Benadryl products late on Friday.

A full list of the over 40 affected products made by McNeil Consumer Healthcare is available at www.mcneilproductrecall.com

“We want to be certain that consumers discontinue using these products,” FDA Commissioner Margaret Hamburg said in a statement.

“While the potential for serious health problems is remote, Americans deserve medications that are safe, effective and of the highest quality. We are investigating the products and facilities associated with this recall and will provide updates as we learn more,” she said.

McNeil said it was recalling the products in consultation with the FDA after discovering manufacturing deficiencies that could affect the quality, purity or potency of the medicines.

The FDA said some of the products may not meet required quality standards, and parents and caregivers should stop administering them to children and switch to generic brands, which are not affected by the recall.

They said consumers should not administer adult strength medicine to infants or children since that could result in serious harm.

Some of the products affected by the recall may contain a higher concentration of active ingredient than specified; others contain inactive ingredients that may not meet internal testing requirements; and others may contain tiny particles, the FDA said.

The FDA said the chance of an adverse reaction was remote, but urged consumers to contact their doctors and the FDA if their children exhibited any symptoms.

McNeil Consumer said it was recalling all lots of the over-the-counter products. The medicines were manufactured in the United States and distributed in the United States, Canada, the Dominican Republic, Dubai, Fiji, Guam, Guatemala, Jamaica, Puerto Rico, Panama, Trinidad and Tobago, and Kuwait.

It said consumers with questions about the recall could contact the company at 1-800-222-6036 or the website.

Source: Reuters

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The FDA plans to pull one more veil off any potential conflicts of interest among the experts recruited for the regulatory group’s influential review panels. The agency posted a proposal to require panel members to disclose the names of any companies or institutions that could create a conflict for them. For the past two years, panel members have only had to state whether they worked for a sponsor or competitor of a drug or device being reviewed.

The agency also plans to provide an idea of the financial interest involved in a potential conflict, offering ranges like $0 to $5,000. Regulators will be able to grant conflict waivers for up to 13 percent of the members meeting on a panel–up from the 5 percent cap it works with now.

“By making fully informed decisions when considering waivers of conflict of interest, and by improving the transparency of those waivers that are granted, FDA can both obtain needed input and maintain external credibility,” says FDA Commissioner Margaret Hamburg in a letter posted on the agency’s website.

FDA panel members bear a big responsibility in the review of drugs and devices. While their votes aren’t binding, regulators typically abide by their opinions.

Source: FierceBiotech

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U.S. regulators are considering ending a safety study on GlaxoSmithKline’s diabetes drug Avandia, the Wall Street Journal reported on Sunday, saying the move could also jeopardize the drug’s presence in the U.S. market.

Avandia has been in the spotlight because of concerns that the drug increases heart attack risks. U.S. Senators Max Baucus and Charles Grassley released a report on the drug in February as well as internal FDA documents, including a 2008 memo from two FDA drug safety reviewers who recommended pulling the drug from the U.S. market.

Glaxo has said the scientific evidence did not establish that Avandia increased heart attack risks and added it had been open in providing information about the drug.

According to the Wall Street Journal report, FDA commissioner Margaret Hamburg wrote a letter to Grassley in late March saying that the agency is reassessing a trial that compares the drug to a drug made by Takeda Pharmaceutical Co called Actos. That trial is also called the TIDE trial, according to the Journal.

FDA Principal Deputy Commissioner Joshua Sharfstein told the Journal that the decision on the trial “cannot be de-linked from the agency’s view of Avandia.”

Sharfstein said no decision had been made on the trial — the FDA has asked a government scientific panel to review the ethics of head-to-head trials, the Journal said.

In late March, Saudi Arabia’s Food and Drug Authority has suspended Avandia for six months, becoming the first healthcare regulator to take such action. The Saudi FDA argued that the potential heart risks of the drug outweigh its benefits.

GlaxoSmithKline and Senator Grassley could not be immediately reached for comment.

Source: Reuters

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The FDA is recommending that healthcare practitioners temporarily suspend use of GlaxoSmithKline’s Rotarix vaccine for rotavirus immunization in the U.S. while the agency learns more about components of an extraneous virus detected in the vaccine. There is no evidence at this time that this finding poses a safety risk.

GSK confirmed that it has notified regulatory authorities of the presence of material from a virus called PCV-1, which is not known to cause illness in humans, according to a company statement. The material was first detected following work done by a research team using a novel technique for looking for viruses. Follow-up tests by GSK and FDA scientists confirmed the academic team’s findings and that viral components have been present since the early stages of the vaccine’s development, including during clinical studies.

Preliminary testing by both the academic researchers and FDA scientists of another licensed vaccine against rotavirus infection, RotaTeq, has not detected components of PCV1.

“We are making clinicians aware of information recently received by FDA about the Rotarix vaccine,” FDA Commissioner Margaret Hamburg says in an agency announcement. “There is no evidence at this time that there is a safety concern.” The agency will gather more information about the PCV1 components in Rotarix. In four to six weeks, it will convene an expert advisory committee and make additional recommendations on the use of rotavirus vaccines. It also plans to seek input on the use of new techniques for identifying viruses in vaccines.

Rotarix and RotaTeq are given by mouth to young infants to prevent rotavirus disease, which can cause severe diarrhea and dehydration and is estimated to be responsible for the deaths of more than 500,000 infants around the world each year, primarily in low- and middle-income countries.

Thomas Breuer, head of global clinical R&D and CMO of GSK Biologicals said the company is discussing the issue with regulatory bodies worldwide.

Source: FiercePharma

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