Avandia

Journal calls for Avandia restrictions

Tracy Staton — Fri, 29 Aug 2008 10:50:52 -0400

In the hardest-hitting assessment of diabetes meds this year, two Wake Forest University researchers say regulators should restrict use of the glitazone class of drugs--which includes the long-suffering Avandia. In an editorial in the journal Heart, the researchers Drs. Sonal Singh and Curt Furberg say that the justification for using these drugs is "very weak to non-existent" given recent studies that highlighted the risks of heart failure and heart attack among patients using GlaxoSmithKline's Avanda. They also cite data from those studies--ACCORD, ADVANCE, and a VA diabetes study--that showed intensive control of blood sugar offered no benefit to cardiovascular health.

In fact, the researchers "question the rationale for leaving rosiglitazlone (Avandia) on the market." Singh said that "safer, cheaper and more effective treatment alternatives are available that do not carry these negative cardiovascular risks in patients with diabetes."

As you all know, the safety of Avandia--and to a lesser extent, its cousin Actos, marketed by Takeda--has been debated for more than a year now, ever since the infamous meta-analysis by Dr. Steve Nissen that linked the GSK med to cardiac risks. The FDA has sifted the data, and it plastered both Avandia and Actos with a "black box" warning of heart failure risks, and cautioned diabetics that these meds aren't proven to cut cardiac problems. Meanwhile, a study in the Journal of the American Medical Association called both Avandia and Actos risky for patients 65 and older, and Canadian regulators restricted its use. Will this editorial spawn a new round of FDA soul-searching? We'll have to wait and see.

- see the report at ScienceDaily
- get the news from Australia's 6Minutes
- get the FreshNews take

Nissen questions approval process for diabetes drugs

Christe Bruderlin-Nelson — Wed, 02 Jul 2008 10:38:51 -0400

Steven Nissen (photo) of the Cleveland Clinic made a statement to the FDA that might hurt diabetes drug manufacturers--especially Bristol-Myers Squibb and AstraZeneca, which are currently in the FDA approval process with diabetes drugs.

A top expert in the field of cardiology, Nissen urged FDA to take a more stringent approach to new drug reviews when it comes to diabetes, and to take extra steps to ensure the drugs also lower cardiovascular risk and ultimately influence lifespan. He said there are so many drugs for diabetes available today that FDA can afford to be more selective. Nissen made his comments on day one of a two-day meeting scheduled to end this afternoon.

Nissen said that drugs that focus only on lowering blood glucose are too simplistic and that diabetes medications must ultimately reduce the risk of cardiovascular disease, as cardiovascular disease is responsible for about 75 percent of deaths in diabetic individuals. However, such a move would change the drug approval process entirely, moving approval based on surrogate endpoints toward later outcomes--and could affect drugs aimed at treating almost every disease state known.

Companies like GlaxoSmithKline and Takeda Pharmaceutical--major players in the $6 billion dollar diabetes market--are also likely to be displeased with the statements, as slower drug approval processes would likely increase manufacturing and approval costs and decrease profits. However, thus far there are no drugs on the market with a proven cardiovascular benefit for over 90 percent of diabetics, those with Type 2 diabetes. Recent controversy about Avandia, charged with increasing risk of heart attack, likely played a role in the planning of the meeting.

Nissen said, "If we take drugs forward that lower blood sugar but increase the risk of death and heart attack, we haven't done diabetics any favors."

- get the full story from the Wall Street Journal
- read more at CNN Money

'No regrets,' says newly retired JP Garnier

Fri, 16 May 2008 06:59:57 -0400

One week after retirement, GlaxoSmithKline ex-CEO Jean-Pierre Garnier (photo) says he has few regrets. Despite the company's lackluster stock performance and decline in price-earnings ratio, he's sanguine about his legacy. He supported vaccines, long an unpopular sector of the drug market, but increasingly a hot spot for development and sales. He broke R&D into smaller units in hopes of boosting innovation, and though the jury's still out on the results, he's sure the move improved productivity. Plus, he forged the merger of Glaxo Wellcome and SmithKline Beecham into "a single company with a very strong culture," he told the Financial Times.

In fact, Garnier says he has no regrets. He admits that he wishes he'd done dozens of things differently--namely spreading the safety data on Avandia around sooner. (The diabetes med has lost a big chunk of market share since a study raised safety concerns last year.) But he says, "The legacy of GSK...is ahead of us."

- see the interview in the Financial Times

'No regrets,' says newly retired JP Garnier

Fri, 16 May 2008 06:59:57 -0400

- see the interview in the Financial Times

Safety questions on Fosamax, Actos, et al.

Tue, 29 Apr 2008 06:59:56 -0400

It must be tough for pharma execs to open a newspaper these days. If reporters aren't going on about falling revenues and patent expirations, they're propagating news about potential safety problems. Take today: Three different studies are linking four big-name drugs to safety risks.

Women who take Fosamax for osteoporosis may be at increased risk of developing an irregular heartbeat, or atrial fibrillation. While the condition isn't necessarily serious, it can lead to stroke. Nevertheless, the Archives of Internal Medicine study concluded that for most women the benefits of Fosamax outweighed the risks.
The epilepsy remedy Dilantin may put young women at higher risk of developing osteoporosis, according to research published in Neurology. Women who took the drug for a year or more showed eight times the bone loss of premenopausal women who didn't take epilepsy meds. And calcium supplementation may not be enough to counteract the bone loss. Full disclosure: This was a small study--only 93 women--and it was partly supported by GlaxoSmithKline, which makes a rival epilepsy med, Lamictal.
Diabetes treatments Avandia and Actos double or triple the odds of non-spinal fractures, especially among patients who took the drugs for a year or more, another Archives of Internal Medicine study found. Previous studies established higher risk of fractures among patients using these drugs, but the new research shows the possible scale of the problem. The study authors said the link needs to be confirmed by additional research.

Now, none of these studies appears likely to send doctors rushing to their prescription pads to switch patients to new meds. But each represents one more obstacle to pharma marketers in an already-difficult environment.

- see the Fosamax coverage from the BBC
- check out the epilepsy story in the Washington Post
- read the diabetes-med news in USA Today
- find US News' take on two of these studies

GSK, Schering-Plough profits drop

Wed, 23 Apr 2008 06:59:58 -0400

When big drugs tank, they take their makers down with them. Witness first-quarter reports from GlaxoSmithKline and Schering-Plough. GSK is suffering on a sharp decline in Avandia sales, reporting a 9 percent decline in profits to $3.9 billion. Sales of the embattled diabetes med--which has been fighting safety concerns since a now-infamous meta-analysis linked it with cardiac troubles last May--dropped by 56 percent in the first quarter.

Trying to put a good face on it, outgoing CEO Jean-Pierre Garnier (photo) said that, without the impact of Avandia and generics, the pharma business would have grown by 7 percent--a meaningless statistic, of course, because Avandia and generics are reality. He should have simply pointed out that GSK had some bright spots, too: Asthma drug sales rose, and two new vaccines got the FDA nod.

Schering-Plough's earnings make Glaxo look positively glowing: The Zetia-and-Vytorin maker saw profits plunge by 48 percent to $291 million. Now, a chunk of that decline came from Organon acquisition costs. The drug maker also blamed increased R&D spending and higher overhead. Sales actually grew by a whopping 57 percent--but that was due to the inclusion of Organon's products. Vytorin and Zetia, the newly controversial cholesterol drugs, toted up $1.2 billion in sales, a 6 percent rise since the first quarter of 2007, but a big drop from fourth quarter figures. (And more declines are on the way, PBMs and managed care companies say.)

- see the Financial Times' take on Glaxo
- read the Wall Street Journal's article on Glaxo
- check out MarketWatch's brief on Schering-Plough
- find the item on further Vytorin and Zetia declines at Pharmalot

GSK rebuked for missing Avandia reports

Wed, 09 Apr 2008 06:59:58 -0400

GlaxoSmithKline got a trip to the FDA woodshed for failing to regularly report post-marketing data it was gathering on the diabetes med Avandia. GSK failed to include updates on as many as 18 different trials in its annual reports to the agency on that med. The agency rebuked GSK, ordering the company to get its act together pronto.

A Glaxo spokeswoman called the missing reports "inadvertent omissions." But that's just the point, the FDA said. The company lacks a system for making sure the right data gets to the FDA at the right time, the agency said. So what other data on which other drugs is also going unreported? "Absent a clear explanation of the extent and cause of these deficiencies and an adequate plan to correct them, we are concerned that similar deficiencies in the post market reporting for your firm's other FDA-approved drugs may exist," the letter states. In fact, the FDA only discovered the missing reports when it conducted an audit last fall, in the wake of safety concerns about the diabetes treatment.

And the warning letter isn't a bureaucratic exercise, either--just ask Pozen, one of GSK's development partners. Last fall's FDA legislation gave the agency new post-marketing oversight powers. GSK's letter states that the agency could deny approval of any new Glaxo products until the company corrects its reporting snafus. Speculation that this provision might affect a GSK/Pozen product Treximet sent the smaller company's stock tumbling Tuesday.

- find the FDA warning letter
- read the article in the International Herald Tribune
- see In Vivo's interpretation of the warning
- check out the story in the Wall Street Journal
- get the Pozen news in Forbes

Related Articles:
Scottish docs call for Avandia freeze
Avandia drop-off erodes GSK profits
Doc leaked Avandia study to GSK
Avandia--Top 10 Warnings and Recalls of 2007

Scottish docs call for Avandia freeze

Mon, 07 Apr 2008 06:59:54 -0400

Some doctors in Scotland want to put Avandia in cold storage. National Health Service consultants are recommending that docs stop prescribing the diabetes med to patients with heart problems, The Scotsman reports. And, the consultants said, GPs should look carefully at patients already taking the drug and stop treatment if those patients have any heart risks.

These recommendations were made to a Glasgow area drug and therapeutics committee, which meets this month. The committee intends to produce guidance for all doctors in that NHS region, Scotland's largest. One source close to the discussions told the newspaper that Avandia is likely to be put on a restricted formulary in the region, meaning that only specialists could prescribe it. In the Dumfries/Galloway region, an official said, the drug is likely to be withdrawn from the formulary completely.

These moves come after the European Medicines Agency in January recommended new warnings for the diabetes med. Avandia's safety has been under scrutiny for almost a year now, since the New England Journal of Medicine published a meta-analysis showing that it may boost the risk of heart attacks by 43 percent and cardiovascular death by 64 percent. That research quickly came under fire--meta-analyses aren't double-blind trials, after all--but it and other data have prompted restrictions on Avandia use in the U.S., Canada, and Europe.

- see the latest in The Scotsman

ALSO: Last week, a small study sponsored by Avandia maker GlaxoSmithKline appeared to show that the diabetes med slowed the progression of artery-clogging in diabetic patients who've had cardiac bypass surgery. Report

Related Articles:
Avandia drop-off erodes GSK profits. Report
Doc leaked Avandia study to GSK. Report
Avandia--Top 10 Warnings and Recalls of 2007. Report
New Avandia warning 'a muddle'. Report

Could full data disclosure avert scandal?

Mon, 24 Mar 2008 07:59:58 -0400

New calls for old drug data in the U.K. have experts second-guessing big drug-safety scandals. If scientists and regulators had had access to every bit of data on Vioxx from the get-go, for instance, would heart attacks and strokes have been averted? Ditto Avandia? "People might have realized that the claims being made for the drug were overblown and coy to the point of being fraudulent," one expert told the Associated Press.

These questions are arising in the wake of a British investigation into GlaxoSmithKline and its antidepressant Seroxat. The government concluded that GSK withheld information on the med's suicide risk for teens, but could not prosecute because withholding that data wasn't illegal under British law because Seroxat wasn't approved for use in kids, just adults. (GSK maintains that it didn't withhold info, anyway.) Officials say they intend to strengthen legislation governing clinical trial info by year's end.

The worry is that safety risks aren't being reported by drugmakers until they absolutely have to. "It would be unwise to assume that this particular case was anomalous," a journal editor said. But other observers emphasized the fact that some side effects aren't known until a drug hits the market and is administered to millions of people instead of a few thousand as in a clinical trial.

- read the story in the International Herald Tribune

Related Articles:
UK patients sue for Paxil withdrawal. Report
Study highlights link between Paxil and suicide. Report
Top 10 Drug Warnings and Recalls of 2007. Report

Ranks of sales reps thinning

Tue, 18 Mar 2008 07:59:56 -0400

Fewer reps are knocking on doctors' doors these days. A consulting firm that advises most of Big Pharma says Pfizer, Sanofi-Aventis, and Bristol-Myers Squibb have all culled their herds of reps. And more companies will be following suit soon.

The cuts aren't a huge surprise; when most of the big drugmakers announced their restructuring-slash-layoff plans, they drew big targets on their sales operations. But other factors come into play, too, Jaideep Bajaj of ZS Associates told the WSJ Health Blog. Companies are backing away from their old, blanket-the-market sales models. Instead of sending five reps to chat up a doctor about the same med, they're sending only two or three.

- read the Health Blog item
- see a video interview with Bajaj

Related Articles:
Top 8 layoffs of 2007. Report
Pfizer to axe 2,200 sales jobs in realignment. Report
What to do with Avandia sales force? Report