* Panel votes 7-4 that benefits outweigh risks
* Concerns about long-term safety, how much benefit
* FDA to make final decision on mirabegron by June 29
By Anna Yukhananov
SILVER SPRING, Md., April 5 U.S. advisers backed
a bladder drug from Astellas Pharma Inc on Thursday,
boosting the company's hopes of gaining approval for a second
treatment for overactive bladder.
A panel of outside advisers to the U.S. Food and Drug
Administration voted 7 to 4, with one abstention, that the
benefits of the once-daily tablet, called mirabegron, outweighed
its possible risks to the heart and liver.
The FDA usually follows the recommendations of its expert
panels and will make a final decision on mirabegron by June 29.
The drug is already approved in Japan.
"I think the drug shows that it's comparable to what we're
using today, for better or worse," said panel member Dr.
Christian Pavlovich, associate professor of urology at Johns
Hopkins Bayview Medical Center.
However, panelists expressed concern the drug's benefits may
not make a huge difference for patients and there were
uncertainties about its long-term safety.
Overactive bladder, whose symptoms include frequent
urination and urgency to urinate, affects about 12 percent to 17
percent of adults in Europe and the United States and 30 percent
to 40 percent of those 75 years and older, Astellas said.
Mirabegron, the first drug in its class, works by activating
a protein receptor, a beta-3 adrenoceptor, in bladder muscles
that help the bladder fill and store urine.
In clinical trials, a 50-milligram dose of the drug reduced
the number of times a person went to the bathroom by about four
times in a week, compared with placebo, and patients taking the
drug had three fewer episodes of urine leakage, or incontinence,
But some advisers said that may not greatly help people who
often go to the bathroom at least eight times a day.
However, the FDA had said clinical trials for the drug only
had to prove it was better than a placebo, prompting the
majority of panelists to vote in favor of mirabegron.
"I would state that the bar was extremely low, that maybe
the FDA needs to reconsider what it requires," said panel member
Dr. Antonio Tito Fojo, program director at the National Cancer
"It was low enough that you could trip over it and get to
the other side," he said.
FDA staff reviewers had been concerned about the drug's
safety, as it raised blood pressure and heart rate in some
clinical trials. There were also rare instances of liver
toxicity and tumors that developed in some patients taking the
drug in trials. The panelists called for the company to do more
trials if the drug is approved.
Astellas, Japan's second-largest drugmaker, said mirabegron
can provide another option to patients beyond current treatments
for overactive bladder.
Many patients drop out of standard treatments after the
first year because of side effects, such as dry mouth, or
because the drug does not work for them, the company said.
Current treatments include the Astellas drug Vesicare, one of
the company's biggest products, which had global sales of 86.7
billion yen ($1.1 billion) in 2010.
With mirabegron, Astellas is hoping to cement its position in
the overactive bladder market, the company said. Mirabegron is
approved in Japan under the trade name Betanis.
Global sales of Vesicare and mirabegron should total over 155
billion yen ($1.9 billion) in the fiscal year ending in March
2015, the company said in its annual report.