Actos diabetes drug
Jury awards plaintiff $6.5 mln in first Takeda Actos trial
A California jury has awarded $6.5 million to a man who accused the Japanese drugmaker Takeda Pharmaceutics of failing to provide an adequate warning that its diabetes drug Actos could cause bladder cancer.
The case in Los Angeles Superior Court is one of over 3,000 lawsuits pending in courts across the country over the medication and was the first to go to trial and reach a verdict. Another 200 suits are consolidated in California state court; some 1,500 are in Illinois state court in Cook County; and another 1,200 are in multidistrict litigation in the U.S. District Court for the Western District of Louisiana.
The plaintiff, Jack Cooper, was a former veteran and retired telephone line worker for Pacific Bell. Plaintiffs' lawyers involved in the litigation said Cooper was not the ideal first case to go to trial because he had a history of smoking, which allowed Takeda to try to blame the cancer on his smoking, said Marc Bern of Napoli Bern Ripka Shkolnik, who is playing a leading role in the consolidated litigation in Cook County.
But Cooper's lawyer, Michael Miller, obtained an early trial date for him under a California statute that allows plaintiffs with grave medical conditions and less than six months to live to jump to the front of the line for trial in state court. Cooper is 79 and suffering from metastatic, terminal bladder cancer.
"This was a special case born of necessity. We were trying to get Mr. Cooper to attend and enjoy the outcome of his own trial before he died," said Timothy Litzenburg, a lawyer at Miller's firm.
After a two-month trial, the jury awarded $5 million in compensatory damages to Cooper, another $1.5 million to his wife, but rejected his request for punitive damages.
Litzenburg said the verdict was an "excellent result" for Cooper and all Actos clients, given that the trial was expedited.
"Takeda empathizes with patients like Mr. Cooper, but we believe the evidence did not support a finding that Actos caused his bladder cancer," said the company's general counsel, Kenneth Greisman. He said the company had acted responsibly, promptly disclosing the drug's safety data to the Food and Drug Administration and other federal regulators.
While the case was not originally selected as a bellwether, it would now serve that function, given that the jury found in Cooper's favor, Bern said.
Takeda has filed motions, asking the judge to rule in favor of the company as a matter of law, and may appeal if the motions are denied, the company said in a statement.
Actos, which was approved by the FDA in 1999 to treat type 2 diabetes, balances blood sugar by making cells more receptive to insulin. The FDA is conducting an ongoing review to determine whether the drug increases the risk of bladder cancer.
The case is Cooper v. Takeda Pharmaceuticals America Inc, California Superior Court, Los Angeles, No. CGC-12-518535.
Source : Thomson Reuters
Actos Bladder Cancer Risk Again Affirmed
The diabetes drug pioglitazone (Actos) appears to raise the risk of bladder cancer, but whether that is a class effect remains unclear, a meta-analysis affirmed.
Any use of a thiazolidinedione was associated with a nonsignificant 45% higher risk in the pooled randomized trials and a significant 15% elevated risk across the observational studies, Jeffrey A. Johnson, PhD, of the University of Alberta in Edmonton, and colleagues found.
Pioglitazone users had pooled risk ratios ranging from 1.22 to 4.30, the group reported online in CMAJ.
The little evidence available on rosiglitazone (Avandia) suggested no increased risk but wasn't conclusive.
"Although the absolute risk of bladder cancer associated with pioglitazone was small, other evidence-based treatments for type 2 diabetes may be equally effective and do not carry a risk of cancer," they wrote.
Type 2 diabetes itself boosts bladder cancer risk by 40%, possibly because elevated insulin levels stimulate the insulin receptors on neoplastic cells that promote cancer growth and division.
The FDA warned last year of a further increase in bladder cancer risk with pioglitazone, now reflected in the drug's product label.
That move followed stronger action against sister drug rosiglitazone in 2010, severely restricting access in the U.S. over concerns about cardiovascular risk.
That risk didn't appear to be a class effect, but whether the bladder cancer risk applies to all thiazolidinediones hasn't been as clear.
Johnson's group pooled results from the available four randomized controlled trials, five observational cohort studies, and one case-control study that included data on incident bladder cancer in type 2 diabetes with ever versus never use of a thiazolidinedione.
Altogether the incidence rate was 53.1 bladder cancer cases per 100,000 person-years on a glitazone (3,643 in 2,657,365 patients across the studies).
For pioglitazone, the one randomized trial suggested a 2.36-fold elevated risk of bladder cancer compared with never having used the drug, but the 95% confidence interval was wide and nonsignificant at 0.91 to 6.13.
However, the one case-control study with pioglitazone pointed to a statistically significant 4.30-fold risk of developing bladder cancer on the drug (95% CI 2.82 to 6.52).
And the pooled results of the cohort studies -- which represented by far the largest number of patients studied at over 1.7 million -- indicated an increased risk with a risk ratio of 1.22 (95% CI 1.07 to 1.39).
The largest of those cohort studies, an analysis of bladder cancer incidence with pioglitazone in the French national healthcare databases that led regulators there to force the drug off the market, also included a rosiglitazone subgroup.
Rosiglitazone showed no significant impact on bladder cancer risk in that study (hazard ratio 1.08, 95% CI 0.92 to 1.26) or in the two randomized controlled trials (pooled RR 0.87, 95% CI 0.34 to 2.23), one of which was not blinded.
"Given the limited evidence among rosiglitazone users, it remains unclear if the association with bladder cancer is a class effect of all thiazolidinediones," Johnson's group wrote.
The researchers cautioned that the major limitation of their meta-analysis was the lack of primary studies to analyze and no individual patient data, which made it impossible to adjust for known bladder cancer risk factors, like smoking and occupational exposures.
The FDA warning suggested that longer duration of pioglitazone use was a greater hazard for bladder cancer, but the studies in the meta-analysis typically didn't provide duration of exposure data.
One study showed a significant increased risk after more than 1 year of exposure to the drug; both that looked for a link after more than 24 months found one.
Another limitation of the meta-analysis was classification by ever versus never use might have been affected by other agents like metformin in combination therapy.
Primary source: CMAJ
Colmers IN, et al "Use of thiazolidinediones and the risk of bladder cancer among people with type 2 diabetes: a meta-analysis" CMAJ 2012; DOI: 10.1503/cmaj.112102.
Source : Medpage Today
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FDA Drug Safety Communication: Updated drug labels for pioglitazone-containing medicines
The U.S. Food and Drug Administration (FDA) is informing the public that the Agency has approved updated drug labels for the pioglitazone-containing medicines to include safety information that the use of pioglitazone for more than one year may be associated with an increased risk of bladder cancer. FDA previously communicated these labeling changes to the public on June 15, 2011 (Drug Safety Communication). The updated drug labels recommend that healthcare professionals should:
- Not use pioglitazone in patients with active bladder cancer.
- Use pioglitazone with caution in patients with a prior history of bladder cancer.
- Contact their healthcare professional if they experience any sign of blood in the urine or a red color in the urine or other symptoms such as new or worsening urinary urgency or pain on urination since starting pioglitazone, as these may be due to bladder cancer.
Actoplus Met (pioglitazone/metformin)
Actoplus Met XR (pioglitazone/metformin extended-release)
Source : FDA (August 2011)
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FDA reviewing safety of Actos diabetes drug
The Food and Drug Administration said on Friday it was reviewing if Takeda Pharmaceutical Co Ltd's blockbuster diabetes drug Actos may be linked to bladder cancer.
Actos is the Japanese drugmaker's top-selling product with sales of about $4 billion a year, but the pill is due to face generic competition after it loses U.S. patent protection in January 2011.
The FDA said early data from an ongoing Takeda study showed no overall association with Actos and bladder cancer. But an increased risk of bladder cancer was seen among patients with the longest Actos exposure and the highest cumulative doses.
The preliminary results are based on 5-year data from an ongoing 10-year trial by Takeda.
"At this time, FDA has not concluded that Actos increases the risk of bladder cancer," the agency said in a statement.
Patients should not stop taking Actos unless told to do so by their doctor, the agency said.
Takeda said the results were early, and the company was committed to completing the 10-year study to get a better picture of bladder cancer rates.
"Looking at the completion of the study will give us the most accurate look at that," Dr. Robert Spanheimer, Takeda medical director for Actos, said in an interview.
Actos is in the same class of drugs as GlaxoSmithKline PLC's Avandia, which has not been associated with bladder cancer but has been linked to heart risks in some studies. Glaxo has said overall scientific evidence does not show that the drug increases heart attack risk.
The FDA is weighing whether Avandia should stay on the market with new restrictions or be removed. In July, an advisory panel voted 20-12 in favor of keeping the drug on the market, although many urged tight restrictions.
Avandia's opponents have argued that the drug is too dangerous to be sold and they have pointed to Actos as a safer alternative. Actos sales have grown while use of Avandia, or rosiglitazone, fell amid a debate about risks.
Concerns about bladder cancer arose with Actos, or pioglitazone, from cases seen in male rats. The drug's prescribing instructions mention those findings.
A guide for patients also notes that bladder cancer occurred in "a few more people who were taking pioglitazone than in people who were taking other diabetes medicines," but adds, "There were too few cases to know if the bladder cancer was related to pioglitazone."
Bladder cancer occurs in an estimated 20 per 100,000 people per year in the United States and is thought to be higher in diabetics, the FDA said.
Source: Reuters 17/9/2010
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