Eli Lilly and Co.’s antidepressant Cymbalta helped people with chronic pain and wasn’t linked to new side effects,
according to U.S. regulators weighing whether to expand use of the drugmaker’s second-biggest product.
Cymbalta doses of 60 milligrams to 120 milligrams reduced pain more than placebos in studies of people with osteoarthritis of the knee or lower back pain, Food and Drug Administration staff said in a report released Tuesday. Outside advisers to the agency were asked to weigh these benefits against the known risk of liver toxicity at an Aug. 19 meeting in Bethesda, Md.
Approval for the millions of Americans with chronic back or knee pain may add more than $500 million, or 16 percent, to Cymbalta’s annual sales, according to Seamus Fernandez, an analyst at Leerink Swann & Co. in Boston who rates Lilly shares “underperform.” Lilly’s application already has been met with several delays, raising doubts that it will be successful.
“Cymbalta has the potential to be a very versatile drug,” said Ira Loss, an analyst at Washington Analysis who has followed the FDA for more than three decades, in an Aug. 3 phone interview. “My guess is that FDA is skeptical. Safety is an issue.”
Shares in Lilly, based in Indianapolis, fell 82 cents, or 2.3 percent, to $34.75 in early trading before the New York Stock Exchange opened. The drugmaker said earlier Tuesday that it will halt development of an experimental treatment for Alzheimer’s disease because the medicine, semagacestat, was associated with worsening cognition and an increased risk of skin cancer.
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. While Cymbalta isn’t approved for kids, it carries the same boxed warning as other antidepressants about the risk of suicidal thoughts and behavior in children and young adults.
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. Lilly's top-selling Zyprexa, an antipsychotic, faces generic competition in 2011.
“The overarching issue with Lilly is the collection of expiring patents,” said Tony Butler, an analyst at Barclays Capital in New York, in an Aug. 4 telephone interview. “Cymbalta unfortunately expires in 2013. It’s not like we’re going to get a lot” of mileage out of a new approval.
Lilly asked for 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 treating pain.
An estimated 10 million Americans have osteoarthritis of the knee, according to Lilly. In a study of 256 people with the disorder reported in January 2009, Cymbalta helped 65 percent of patients feel better, compared with 44 percent who felt better on placebo. Another measure of pain and stiffness didn’t show a statistically significant benefit for Cymbalta.
Once-daily Cymbalta helped reduce the severity of chronic low back pain in a 401-person study reported in February. Thirty people in the Cymbalta group withdrew from treatment because of side effects such as nausea, headache, dry mouth, constipation and dizziness, compared with 11 people in the placebo group. A separate study reported in September found that reduction in lower back pain was maintained after 41 weeks.
It’s unusual for the FDA to grant broad approval for “chronic pain” instead of a more specific condition, said Kurt Kroenke, a professor of medicine at Indiana University’s School of Medicine in Indianapolis who has consulted for Lilly.
Many painkillers are sold cheaply as generics. Patients usually first try acetaminophen and ibuprofen, which are widely available over the counter. 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, Kroenke said.
“A number of patients with more moderate or severe pain probably need medicines from other classes,” Kroenke said in an Aug. 9 telephone interview. “If we had options before we had to move on to opiates, that would be beneficial.”