It has long been thought that Cymbalta (generic name duloxetine) would be the second medication to receive FDA approval for the treatment of fibromyalgia. However, the disappointing results of the third phase III efficacy study could stall Lilly’s quest for approval.
The 27-week phase III clinical trial randomized 330 fibromyalgia patients to either a 60 mg or 120 mg per day dose or to a placebo. Patients were allowed to switch between the 60 and 120 mg dosages during the study according to efficacy and tolerability.
Cymbalta failed to achieve a statistically significant difference over the placebo in the primary outcome measures. The mean reduction in pain severity (measured by the Brief Pain Inventory) was 1.62 for Cymbalta and 1.12 for the placebo. The patients’ impressions of improvement scores averaged 3.42 for Cymbalta and 3.73 for the placebo. Cymbalta also showed no significant improvement in physical function. This study stands in stark contrast to earlier clinical trials, where Cymbalta scored significantly better than the placebo on pain severity measures.
In secondary outcome measures, Cymbalta fared better, achieving statistical significance in several areas. One of the most notable positive results was on the mental component of the 36-point Short Form Health Survey. Subjects on Cymbalta showed a 3.4-point improvement compared to only 0.8 with the placebo.
Other interesting statistics from the trial: 14.9 percent of subjects taking the placebo quit the study early due to lack of efficacy compared to 7.4 percent of those taking Cymbalta; 18.5 percent taking Cymbalta discontinued the study because of adverse side-effects compared with 11.3 percent taking the placebo; more than 80% of the subjects in both groups reported some type of adverse effect during the study.
What Happens Next?
Lilly has filed an application with the FDA to market Cymbalta for the treatment of fibromyalgia. Will these results prevent Cymbalta from receiving FDA approval? Possibly. It could also be delayed if the FDA decides further studies are needed. Or, they could decide that a preponderance of evidence is sufficient and approve it. The decision is expected sometime in 2008.
Cymbalta, a norepinephrine-serotonin reuptake inhibitor (NSRI), has already been approved by the FDA for treating depression, generalized anxiety disorder and diabetic neuropathy. Since it already has approval for other illnesses, doctors can currently prescribe Cymbalta off-label for fibromyalgia.
Published On: November 19, 2007