drug safety

Study reaffirms safety flags for last-minute meds

Tracy Staton — Thu, 03 Jul 2008 08:52:05 -0400

Remember that study that seemed to show that drugs FDA approved on deadline were more likely to end up with safety problems? Since its March publication in the New England Journal of Medicine, FDA hit back, saying that the Harvard professor who did the research made mistakes. Well, now Daniel Carpenter admits that FDA did find mistakes--but when he corrected those mistakes and added more recent data, he said, his original finding still holds.

Now, Carpenter says, the 88 drugs approved on deadline between 1993 and 2005 had a 15 percent chance of getting tagged with severe safety problems: Either a black-box warning or complete withdrawal. For the 226 other drugs approved the rate was just 5 percent. That compares with 14 percent and 3 percent, respectively, in the original published study. And when Carpenter extended that data through 2007, both groups got red flags: 20 percent of on-deadline drugs were withdrawn or got a black-box warning compared with 9.7 percent of other drugs. And, Carpenter says, he may have missed some warnings in his earlier study, but the FDA data omitted "a whole bunch" of them.

FDA didn't comment for the Wall Street Journal, but when the first study was released, said that its own records showed no statistically significant difference in safety performance among those drugs approved right before deadline and those that weren't.

- see the WSJ article

EMEA advises against anemia meds

Tracy Staton — Fri, 27 Jun 2008 09:32:17 -0400

European regulators are taking a stand against anemia drugs. The European Medicines Agency says cancer patients with a "reasonably long life-expectancy" should get blood transfusions instead of taking the meds, such as Amgen's Aranesp and Johnson & Johnson's Eprex (sold in the U.S. as Procrit). The EMEA guidance follows an FDA advisory committee's recommendation that the drugs shouldn't be given to cancer patients who might be cured. That's because some studies found a link between the drugs and tumor growth.

Analysts were "somewhat surprised" by the EMEA's "aggressive stance" on the meds, the Wall Street Journal Health Blog notes. No doubt it will further erode sales of the drugs, which already have taken a beating because of safety concerns. In Europe, half of anemia med use is in cancer patients, and some 40 percent of those patients could be affected by the EMEA warning.

- read the Health Blog item

U.S. Paxil probe broadens

Tracy Staton — Fri, 20 Jun 2008 09:20:10 -0400

More government watchdogs appear to be boarding the Paxil investigation train. The Justice Department is coordinating a probe that includes Colorado's Justice folks and the Boston U.S. attorney's office. GlaxoSmithKline had already disclosed the Colorado investigation and confirmed the rest in today's Wall Street Journal. Investigators are gathering documents and depositions about Paxil's potential link to suicidal behavior, at least in part from plaintiff's lawyers representing families suing the drugmaker, and about GSK's portrayal of those risks to doctors and the FDA, the WSJ says.

Glaxo says it's cooperating with the investigation and that it can't comment further. In the past, the company has said that it "acted properly and responsibly" in testing Paxil and passing on trial data to regulators.

According to the WSJ, the probe is particularly focused on Glaxo's submissions to the FDA about Paxil and suicidality when the drug's approval was pending. Investigators also were anxious to get their hands on some documents, under court seal, that disputed GSK's research conclusions on suicidality risks. GSK gave the Justice Department those documents, stipulating that they not be passed along to the FDA.

You'll recall that last week, Sen. Charles Grassley demanded an FDA investigation of Paxil's 1992 approval. That followed a years-long U.K. investigation that recently ended with no charges against GSK because British laws on data-sharing are unclear.

- read the Wall Street Journal story

Misoprostol linked to deaths with off-label use

Christe Bruderlin-Nelson — Wed, 18 Jun 2008 06:22:46 -0400

At least eight women have died from shock complications of an acute Clostridial infection following a medical abortion using a combination of mifepristone (Mifeprex) and misoprostol (Cytotec).

A new animal trial linked misopristol, the abortion drug used orally in combination with RU-486, to fatal infections in seven of the women. These seven women used the drug as a vaginal suppository, rather than as an oral agent. The drug has been deemed safe when given orally, but its off-label use might cause immune system suppression that allows a certain bacterium to achieve deadly virulence.

According to Arnoff, "When the drug is given orally, it does not appear to have a suppressive effect on reproductive tract immunology." However, "If the drug is applied directly to the reproductive tract, that's where we can see suppression of the immune system." The study appears in the online version of the Journal of Immunology. The researchers found that misoprostol--when used off-label--dramatically increased the virulence and lethality of the bacteria by about 50-fold.

- see the story on Med Page Today
- read the Journal of Immunology study abstract

Related Article:
Chinese RU-486 maker sold tainted drugs

Enbrel, antipsychotics draw warning fire

Tracy Staton — Tue, 17 Jun 2008 11:04:57 -0400

Warning! Warning! Two new safety stories from the FDA hit the press yesterday: One on Amgen's rheumatoid arthritis and psoriasis drug Enbrel, and one on older antipsychotic meds such as Haldol and Thorazine.

First, the agency wants to beef up labeling for Enbrel to include a warning that, when used in children, the drug carries the risk of death. Enbrel is up for pediatric approval for use in psoriasis--currently it's only approved for psoriasis use in adults -- and in preparation for the advisory committee discussion tomorrow, FDA staffers combed the adverse events database. They found some serious problems in kids using Enbrel, such as malignancies, infections, and neurological problems, many of them life-threatening--and some deadly. Given the fact that the number of children on Enbrel is fairly small, these serious adverse events are a red flag, FDA said. The agency is recommending that the label be changed, regardless of whether the drug gets the additional psoriasis nod.

Meanwhile, the FDA warned doctors that dementia patients using older antipsychotics appear to be at an increased risk of dying. A "black box" warning is going on the meds, which are sometimes used off-label to calm aggressive or out-of-control dementia patients. It's similar to the cautionary tale on newer antipsychotics, a.k.a. atypicals, which got a death-risk black box for dementia use three years ago.

- see the Wall Street Journal article
- check out the Washington Post story

Overseas oversight gets serious - FDA trends

Maureen Martino — Sun, 15 Jun 2008 16:24:11 -0400

The heparin scandal threw into sharp relief just how difficult it is to regulate drug ingredients produced overseas. No one was quite sure where in the supply chain the heparin was tainted, and the FDA and China traded blame over the fiasco. FDA Comissioner Andrew Von Eschenbach didn't escape blame though; he found himself in the hot seat again at a Congressional hearing. The House Committee on Energy and Commerce grilled the agency chief about foreign oversight and scolded him for safety lapses that occurred on his watch, including the big heparin debacle.

While most drugmakers draw ingredients from overseas, the problems with heparin highlighted just how difficult it is to regulate a drug's supply chain from start to finish. With an increasing amount of drugs and drug ingredients being imported from India, China and the like, the need is increasing for more rigorous overseas inspection. In response, the FDA is working to establish five satellite offices in India, China, Central and South America and the Middle East. But the FDA is already running into a nest of red tape with its China office and undoubtedly more problems lay ahead as the FDA grapples with drug safety on a global scale.

One thing is for sure: in the coming years, the FDA won't be caught flat-footed the way they have been recently, and drugmakers better be prepared to deal with tighter regulations.

FDA: Warning imminent for epilepsy meds

Tracy Staton — Thu, 12 Jun 2008 10:51:05 -0400

Apparently drugmakers' fears of new labeling for epilepsy drugs were well founded. The agency says it's very close to a deal with the companies on the labeling changes. And FDA has posted its written review of the data on suicidal thoughts and behavior among patients using the meds. The upshot: Twice the risk of suicidal thoughts or behavior among patients using one of the meds versus those using placebo (0.43 percent versus 0.22 percent). And, the agency said, the risk was consistent across all 11 drugs it studied.

An FDA advisory panel will meet next month to mull over the data themselves. But sources told USA Today that the labeling could be changed even in advance of that meeting.

- read the report
- check out the Pharmalot item

Analyst: Singulair drop threatens Merck

Tracy Staton — Tue, 10 Jun 2008 10:22:04 -0400

Just what Merck doesn't need: Its asthma-and-allergy med Singulair is losing ground, with new scrips down year-over-year for 13 weeks straight. For the week ended May 30, the drop was 16 percent, and year to date, Singulair has fallen off by 4 percent. That's according to Sanford Bernstein analyst Tim Anderson, who's worried that Singulair performance might seriously undermine Merck's projected 2008 sales growth. The company has projected worldwide year-over-year increases in Singulair sales of 8 percent to 13 percent.

Anderson speculates on possible causes for the reversal. A light allergy season? Competition from a newly OTC Zyrtec? Headlines about the FDA's flagging Singulair as having a potential psychiatric problems? (Merck says safety isn't the reason for the slowdown.)

"As Singulair is Merck's single biggest drug--with 2007 sales of $4.3 billion, up 19 percent year-over-year, and representing 18 percent of total company sales--these trends are worrisome," Anderson writes in a note to investors. "Internationally, Singulair performance may well be better, but the U.S. accounts for nearly three-quarters of total Singulair sales." Even if scrips stopped dropping now, he notes, the drug would have a tough time making those sales goals.

- read the Pharmalot post

FDA might finally get its $275 mil

Tracy Staton — Tue, 10 Jun 2008 09:29:36 -0400

The FDA funding question has come full circle. First, the government's watchdog, the General Accounting Office, said FDA needed more money to do its job effectively. Then Congress asked FDA officials--repeatedly--to name a figure. A few months of that prodding finally yielded a number from Commissioner Andy von Eschenbach: $275 million.

Now, the Bush administration has seconded that figure, asking Congress to give FDA the money. HHS Secretary Michael Leavitt urged "Congress to act quickly to enhance the safety of food and medical products." With the added funds, FDA would open offices in China, India and Central America and hire another 490 people on top of the new employees it's already adding, bringing the total workforce expansion to 1,500, or 10 percent.

Apparently the big salmonella outbreak, linked to raw tomatoes, was the straw that broke the government's back. Coming on the heels of contaminated dog food, toothpaste, heparin, and more, the tainted tomatoes became one headline too many.

- read the New York Times story

Grassley probes dog-drug relaunch

Tracy Staton — Thu, 05 Jun 2008 20:42:35 -0400

It's not just human drug safety that gets Sen. Chuck Grassley into letter-writing mode. When the FDA decided to let a reformulated version of a Wyeth heartworm drug for dogs back onto the market, Grassley fired off a missive to Commissioner Andrew von Eschenbach. What he's worried about is: a. whether the new formula was actually tested on dogs (he alleges the tests were only done on guinea pigs), and b. whether any of the agency meetings about putting the drug, ProHeart, back up for sale involved FDA safety officials. Considering the way people reacted to the big pet food recall last spring, Grassley's vigilance on behalf of U.S. canines could win him some friends in the dog-owner set.

The pharma set? Not so much. Grassley's letter put a safety spin on what Wyeth probably hoped would be an uneventful, but successful reintroduction of ProHeart. The company pulled the previous version of the med in 2004 after reports that 500 dogs died after taking it. Then, Congress held hearings into the FDA's handling of the drug when a staffer said she'd raised questions about its safety--but her superiors shot her down. The new formula, in fact, is coming out under a restricted-distribution program, and its label includes warnings to refrain from administering it within a month of a vaccine.

- read the CNN Money story