Drugmaker Eli Lilly and Co said on Friday it withdrew an application to market its anti-depressant Cymbalta (duloxetine HCl) for the management of chronic pain because US health regulators raised questions about the drug's effectiveness and dosing.
Cymbalta is Eli Lilly's second best seller, after the anti-psychotic Zyprexa. In the first nine months of 2008, the company reported worldwide Cymbalta sales $1.98 billion.
Lilly said it planned to resubmit the application in the first half of 2009, adding data from "a recently completed positive study in chronic osteoarthritis pain of the knee".
The company said the decision does not affect duloxetine's FDA-approved indications for major depressive disorder, generalised anxiety disorder, management of diabetic peripheral neuropathic pain and management of fibromyalgia.
Lilly submitted the chronic pain application in the second quarter of 2008 based primarily on outcomes of three clinical trials: one positive study in chronic osteoarthritis pain of the knee and two studies, -- one positive and one that is supportive but didn't meet its primary endpoint -- in chronic low back pain. In discussions between Lilly and the FDA, agency reviewers raised questions about efficacy and dosing that revolved primarily around statistical methodology and study design.
Lilly said it made its decision to pull the supplemental New Drug Application for Cymbalta, or duloxetine HCl, after US Food and Drug Administration reviewers questioned the design of supporting Lilly studies and statistical methodology.
"This was a difficult decision, but we believe the updated data package will give the FDA a broader basis for reviewing our application," said John Hayes, M D, a Lilly Research Laboratories vice president at Lilly.
The maker of schizophrenia drug Zyprexa, osteoporosis treatment Evista, and cancer drug Alimta, said it plans to resubmit the application to the FDA in the first half of 2009, after adding data from a recently completed study in chronic osteoarthritis pain of the knee.
The decision does not affect the drug's existing FDA-approved indications for major depressive disorder, generalized anxiety disorder, management of diabetic peripheral neuropathic pain and management of fibromyalgia, Lilly said.
Chronic pain affects more than 50 million Americans and pain is a major cause of work absenteeism, underemployment and unemployment. Serotonin and norepinephrine in the brain and spinal cord are believed to both mediate core mood symptoms and help regulate the perception of pain.
"Based on preclinical studies, Duloxetine is a balanced and potent reuptake inhibitor of serotonin and norepinephrine that is believed to potentiate the activity of these chemicals in the central nervous system (brain and spinal cord)" Eli Lilly said in a statement announcing its plans to resubmit its appliacation.
It also said, "While the exact mechanism of action of Duloxetine is unknown, scientists believe its effects on depression and anxiety symptoms, as well as its effect on pain perception, may be due to increasing the activity of serotonin and norepinephrine in the central nervous system."
Duloxetine is approved in the United States for theDuloxetine is approved to treat major depressive disorder and generalized anxiety disorder, and to manage diabetic peripheral neuropathic pain and fibromyalgia in adults of 18 years and older.
Duloxetine is not approved for use in pediatric patients, as the company said that antidepressants can increase suicidal thoughts and behaviour in children, adolescents, and young adults. Patients should call their doctor right away if they experience new or worsening depression symptoms, unusual changes in behaviour, or thoughts of suicide.
Duloxetine is approved only for adults 18 and over but advises users to be especially observant within the first few months of treatment or after a change in dose for any side effects.
Duloxetine is not for everyone. Patients should not take Duloxetine if they have recently taken a type of antidepressant called a monoamine oxidase inhibitor (MAOI), are taking Mellaril (thioridazine), or have uncontrolled glaucoma.
Lilly cautions that patients should speak with their doctor about any medical conditions they may have including kidney problems, glaucoma, or diabetes. Patients should talk to their doctor if they have itching, right upper belly pain, dark urine, yellow skin or eyes, or unexplained flu-like symptoms, which may be signs of liver problems. Severe liver problems, sometimes fatal, have been reported.
They should also talk to their doctor about alcohol consumption. Patients should tell their doctor about all their medicines, including those for migraine, to avoid a potentially life-threatening condition. Taking Duloxetine with NSAID pain relievers, aspirin, or blood thinners may increase bleeding risk. Patients should consult with their doctor before stopping Duloxetine or changing the dose and if they are pregnant or nursing.
Patients taking Duloxetine may experience dizziness or fainting upon standing. The most common side effects of Duloxetine include nausea, dry mouth, sleepiness, and constipation. This is not a complete list of side effects.
Eli Lilly and Company was founded in 1876 by a pharmaceutical chemist, Eli Lilly, after whom the company was ultimately named and is one of the world's largest corporations, with global headquarters in Indianapolis, Indiana, in the United States.
A Fortune 500 corporation, Eli Lilly had revenues of $18.6 billion in 2007, making it the 148th largest company in the United States and the 10th largest corporation by global pharmaceutical sales. The company is publicly traded on the New York Stock Exchange and is a member of the S&P 500 stock index. It employs more than 40,000 people around the globe.