Eli Lilly and Company (INDIANAPOLIS, Indiana) announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has adopted a negative opinion on a Cymbalta^® (duloxetine hydrochloride) application for the treatment of fibromyalgia, recommending the refusal of a change to the marketing authorization for Cymbalta/Xeristar 30 mg and 60 mg gastroresistant capsules. The companies that applied for authorization were Eli Lilly Nederland B.V. (for Cymbalta) and Boehringer Ingelheim International GmbH (for Xeristar). They may request a re-examination of the opinion within 15 days of receipt of notification of this negative opinion.

The results of five studies involving a total of 1718 adults with fibromyalgia were presented to the CHMP to support the application. Four of the studies were short-term, lasting between 3 and 6 months, and comparing Cymbalta/Xeristar with placebo in a total of 1411patients. The fifth, a long-term study, compared the effects of two doses of Cymbalta/Xeristar over a year in 307 patients. In all of the studies, the main measures of effectiveness were based on changes in the patients’ symptoms, particularly pain levels, and their overall state of health. These were measured using standard scales and questionnaires.

The CHMP was concerned that the effectiveness of Cymbalta/Xeristar in treating fibromyalgia had not been shown sufficiently. In the short-term studies, the CHMP considered that the effect of Cymbalta/Xeristar was too small to be relevant for patients: there was no clear demonstration of improvement in symptoms, and the modest effects of Cymbalta/Xeristar could be due to the medicine’s effect of improving the patients’ mood. The CHMP also concluded that the long-term study was insufficient to show the effectiveness of the medicine and that a long-term study comparing Cymbalta/Xeristar with placebo would be needed. The CHMP was of the opinion that the benefits of Cymbalta/Xeristar in the treatment of fibromyalgia did not outweigh its risks. Hence, the CHMP recommended that the change to the marketing authorization be refused.

Duloxetine is a serotonin-noradrenaline reuptake inhibitor (SNRI), and these neurotransmitters are thought to be involved in fibromyalgia. Duloxetine was approved in the US for the management of fibromyalgia in June 2008 by the US FDA.

In Europe, duloxetine has been approved for the treatment of diabetic peripheral neuropathic pain (DPNP), major depressive episodes, generalized anxiety disorder (GAD) and stress urinary incontinence (SUI). Cymbalta/Xeristar was expected to be used in fibromyalgia patients with or without depression. No medication has been approved in Europe for the treatment of fibromyalgia.