* Two studies fail to confirm earlier Avastin results
* Roche drops 4 percent in Swiss trading
* Advisory panel to weigh data on Tuesday
* Marketing restrictions could depress sales
(Adds closing shares, additional Roche comment, details on
drug's effectiveness, side effects, price)
By Lisa Richwine
WASHINGTON, July 16 The benefits of Roche AG's
ROG.VX Avastin may not outweigh the risks for patients with
advanced breast cancer, U.S. reviewers said on Friday, knocking
the Swiss company's stock down 4 percent on fears that
regulators could restrict marketing of the blockbuster drug.
Two studies of Avastin, Roche's top-selling drug, failed to
show the level of benefit for advanced breast cancer patients
seen in an earlier trial. A Food and Drug Administration
advisory panel will review the Avastin data on Tuesday.
Investors are watching to see if the FDA might revoke
Avastin's approval for breast cancer.
If that happens, the company could no longer promote the
drug for that disease. Doctors could still prescribe it for
that use as it would remain on the market with approval for
other cancers, but sales could fall.
"There is a significant probability the breast cancer
indication is withdrawn" in the United States, Berenberg Bank
analysts said in a research note. Other analysts said they
thought the advisory panel would back the breast cancer use.
About $1.2 billion of Avastin's projected $6.5 billion in
sales this year will come from breast cancer use worldwide,
Sanford Bernstein analysts estimated.
Avastin won clearance for breast cancer in 2008 under a
shorter approval process, but Roche was required to run two
follow-up studies to confirm the drug's effectiveness and
receive full approval.
Those studies "failed to confirm the magnitude of
(progression-free survival) improvement" seen in the initial
breast cancer trial, the FDA staff said.
Progression-free survival is the time patients live without
their cancer getting worse. Avastin, which is given
intravenously, extended that time period by 5.5 months in the
intial study. In the two later studies, the time ranged from
about one month to nearly three months.
The level of improvement for the latter studies was "not
clinically meaningful," the FDA reviewers said, adding that the
"risk-benefit ratio" of Avastin plus chemotherapy "may not be
considered favorable." The known risks include gastrointestinal
perforations, bleeding and blood clots.
The agency wants input from the advisory panel on "whether
clinical benefit has been demonstrated," the summary said.
Avastin did not extend patients' overall survival in any of
Kepler Capital Markets analyst Martin Voegtli said the
study results were not new and that he expected most panelists
to support full approval of Avastin as a first-choice treatment
for advanced breast cancer.
"The reaction in the Roche stock is overdone," Voegtli
said. FDA documents for advisory panels "tend to focus more on
the negative aspects, so I am not worrying about this too much
at this point."
The FDA usually follows panel recommendations. A final FDA
ruling is due by Sept. 17.
Helvea analyst Karl-Heinz Koch also said he expected a
positive outcome. He said did not think the FDA would withdraw
the approval after doctors had been using the drug to treat
breast cancer for several years.
Roche said its research supported Avastin, known
generically as bevacizumab, in advanced breast cancer. The
company is asking the FDA to expand the approval to include use
with other types of chemotherapy.
Dr. Philippe Bishop, a Roche vice president, said the rate
of serious complications was low and the extended time without
cancer growing was meaningful for patients with advanced breast
cancer. At that stage the disease cannot be cured and the goal
is to stablize patients as much as possible, he said.
"Avastin is helpful for patients with metastatic breast
cancer," he said in an interview. "We remain convinced Avastin
should be a choice in this setting."
The drug's wholesale cost is about $8,000 per month for
advanced breast cancer. Roche limits the annual cost for any
FDA-approved use to about $57,000.
Roche stock lost 4.2 percent in Swiss trading after the FDA
review was released.
(Reporting by Lisa Richwine; Additional reporting by Katie
Reid in Zurich; Editing by Lisa Von Ahn, Leslie Gevirtz)