* FDA will ask panel about safety, efficacy
* Suicides, weight loss, cancer among safety issues
* Forest shares fall 1.4 pct
(Adds FDA staff, analyst comments; updates shares)
By Lisa Richwine
WASHINGTON, April 5 U.S. drug reviewers
questioned the effectiveness of a proposed lung drug from
Forest Laboratories Inc FRX.N and Nycomed [NYCMD.UL] on
Monday and raised concerns about suicides and other safety
Forest shares were down 1.4 percent to $30.99 in afternoon
trading on the New York Stock Exchange, after shedding as much
as 3.8 percent earlier in the session.
Food and Drug Administration reviewers, in documents
released on Monday, said improvements in lung function seen
with the drug, Daxas, were "quite modest" in company studies of
patients with chronic obstructive pulmonary disease (COPD).
Safety issues included a slightly higher rate of cancers,
as well as problems previously linked to Daxas' class of drugs,
such as nausea, diarrhea and weight loss.
"Of significant concern are the occurrence of three
completed suicides and two suicide attempts," the FDA staff
said in a summary prepared for an advisory panel that will
review the drug on Wednesday.
The fate of Daxas, a once-daily pill, is key to Forest as
the company tries to build its portfolio ahead of the 2012
patent expiration for its huge-selling antidepressant Lexapro.
Forest holds U.S. rights to the drug, which was originally
developed by Nycomed, a privately held Swiss drugmaker aiming
for an initial public offering that could be one of the biggest
for the pharmaceutical sector in years.
Lazard Capital Markets analyst Bill Tanner said he did not
think any of the concerns would derail approval of Daxas
because of the great need for new COPD treatments.
"I think it's approvable. Clearly there's an unmet medical
need. This is doing something that other COPD drugs don't," he
"We're pretty comfortable thinking it's probably a $500
million drug and it gets approved," he said.
COPD, or "smoker's lung," is a potentially fatal lung
disease that causes breathing trouble and chronic coughing. An
estimated 80 million people worldwide have moderate to severe
COPD. Smoking is a major cause.
Daxas, known generically as roflumilast, works by
inhibiting an enzyme called PDE4 that is linked to
Diarrhea, weight loss and nausea are known effects of PDE4
inhibitors. Jefferies analyst Corey Davis said cancer and
suicides were unexpected safety issues that would draw
discussion at the panel meeting.
"The totality of the data warrant a vote in favor of Daxas
approval, but the stock is likely to be choppy until the final
votes are tallied after the close on Wednesday," Davis wrote in
a research note.
FDA reviewers said none of three men who committed suicide
had histories of depression. Two of them had stopped taking
Daxas about three weeks earlier. Of the suicide attempts, one
woman had a history of depression and the other had made a
previous suicide attempt.
Psychiatric problems such as depression, insomnia and
anxiety were reported in 6 percent of patients who took the
highest Daxas dose, compared with 3 percent of placebo
Cancer rates were 1.5 percent for Daxas patients compared
with 1.3 percent with a placebo, Davis said.
"These are lifelong smokers and it is not unusual to see
lots of cancers," said Davis, but added: "It will come down to
a judgment call."
In January, Forest narrowed the proposed use of Daxas from
broad treatment of COPD to reducing exacerbations of the
disease, the FDA staff said. The late change is "problematic
because it shifts the focus of the efficacy analysis," the
Lazard analyst Tanner said the switch could delay a final
decision beyond the current mid-May deadline.
Forest, in separate documents prepared for the advisory
panel, said the drug had "demonstrated efficacy in reducing the
rate of moderate and severe exacerbations (of COPD) and in
improving lung function" and had an "additive effect on top of"
The company said potential side effects were acceptable.
The number of suicides and attempts was low and a review of
the cases "does not suggest a causal relationship" with Daxas,
Forest said. Patients should be monitored for severe
psychiatric symptoms "as an added precaution," the company
The panel is set to vote on whether to recommend approval
of Daxas. The FDA usually follows panel recommendations.
(Reporting by Lisa Richwine, editing by Gerald E. McCormick)