Eli Lilly & 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 lower back pain.
Outside advisers to the Food and Drug Administration voted 8-6 today in favor of broader Cymbalta use over concerns that it can cause liver damage and may not work for all patients. 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 sales of Cymbalta, the company’s second-biggest medicine, may increase by more than $500 million, or 16 percent, with approval for the tens of millions of Americans with musculoskeletal 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, at a meeting today in Bethesda, Maryland.
Lilly fell 50 cents, or 1.4 percent, to $34.28 at 4 p.m. in New York Stock Exchange composite trading. The Indianapolis- based drugmaker has fallen 4 percent so far this year, compared with a 7.5 percent decline in the 11-member Standard & Poor’s 500 Pharmaceuticals Index.
The dissenting members of the panel were worried about potential liver risks with Cymbalta and the lack of benefits shown in one of two studies testing the drug for osteoarthritis of the knee. They also called for larger trials that follow patients for longer than the 13 weeks Lilly used to show effectiveness in osteoarthritis of the knee and lower back pain.
“It’s a marginal advance, and to puts tens of millions at risk based on studies of a few hundred patients is not warranted,” said panel member Thomas Boyer, a professor of medicine at the University of Arizona College of Medicine in Tucson.
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.
“For people living with chronic low back pain and chronic pain due to osteoarthritis, we believe it’s important they have different treatment options available since responses to medications can be highly individualized,” said Robert Baker, Lilly’s global development leader for psychiatry and pain disorders. “We see today’s vote as an important step in potentially making Cymbalta available to a broader pain population.”
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 today they aren’t comfortable generally recommending Cymbalta for all types of chronic pain.
“The division is not asking you if you can approve this for the whole world of chronic pain,” Bob Rappaport, head of the FDA’s Division of Anesthesia and Analgesia Products, told the panel. “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 associated with worsening cognition and an increased risk of skin cancer.