Lilly gains panel’s backing to expand Cymbalta use

Eli Lilly and Co., the drugmaker whose top three products face generic competition within three years, won a U.S. panel’s
backing to expand use of the antidepressant Cymbalta in chronic knee and back pain.

Outside advisers to the Food and Drug Administration voted 8-6 Thursday in Bethesda, Md., in favor of a broader use of Cymbalta
on the basis of studies in lower back pain and osteoarthritis of the knee. The FDA usually follows its panels’ recommendations,
though it isn’t required to do so.

Lilly needs revenue growth from aging products as new drugs struggle to reach the market. Annual revenue from Cymbalta, the
company’s second-biggest seller, may increase by more than $500 million, or 16 percent, with approval for the millions
of Americans with chronic back or knee pain, according to Seamus Fernandez, an analyst at Leerink Swann & Co. in Boston.

“I think it will be a very useful drug for a significant number of patients,” said panel chairman Jeffrey Kirsch,
chair of the Department of Anesthesiology and Perioperative Medicine at the Oregon Health & Science University in Portland.

Sales of Cymbalta were $3.07 billion last year, accounting for 14 percent of Lilly’s revenue. The drug is scheduled
to lose U.S. patent protection in 2013, along with the insulin Humalog, which ranks third in revenue. Top-selling Zyprexa,
an antipsychotic, faces generic competition in 2011.

Lilly asked for broad approval in chronic pain in the second quarter of 2008 before withdrawing the application after the
FDA raised concerns about study design and statistical methodology. The application was resubmitted in June 2009. An advisory
panel review initially slated for January was canceled so regulators could have more time to consider new information pertaining
to the drug’s “benefit-risk balance” in pain.

FDA officials said Thursday they aren’t comfortable generally recommended Cymbalta for all types of chronic pain and
will instead consider approval for “musculoskeletal pain.”

“This is a fairly narrow broad indication” for Lilly, Bob Rappaport, head of the FDA’s Division of Anesthesia
and Analgesia Products, told the panel. “The division is not asking you if you can approve this for the whole world
of chronic pain. Based on our current thinking, they have not done enough studies in the entire population to warrant that
indication.”

Through last year, about 6.5 percent of Cymbalta prescriptions were for headaches and nerve pain, including “chronic
pain syndrome,” and 7 percent were for diseases of the musculoskeletal system, including arthritis and back pain, the
FDA staff said in a report released this week. While companies can’t market drugs without the agency’s clearance,
doctors can prescribe them for so-called off-label uses.

“People who have chronic pain very often have depression as well, so something that can treat both is just added benefit,”
said Kelly Posner, director of the Center of Suicide Risk Assessment at Columbia University, in a phone interview.

Patients with chronic pain usually first try acetaminophen and ibuprofen. Older antidepressants known as tricyclics are also
recommended in clinical guidelines, though they aren’t approved for chronic pain. Doctors try to limit use of oxycodone,
hydrocodone and other opiate narcotics because they can be misused or lead to addiction.

Cymbalta was cleared by the FDA in 2004 for adults with major depression. Approval was extended to treating nerve pain in
diabetics, generalized anxiety disorder and fibromyalgia, a condition characterized by chronic fatigue and muscle and joint
pain. The drug carries warnings about potential liver risks, low blood pressure, seizures, loss of consciousness, and suicidal
behavior in children and young adults.

Investors and analysts have looked to Lilly’s experimental Alzheimer’s disease therapies to replace revenue lost
to generic copies of Cymbalta and Zyprexa. The company said Aug. 17 that it would abandon one of the Alzheimer’s drugs
in late-stage clinical trials because it was associat