Different primary or co-primary endpoints have been often utilized in clinical setting for newly investigated drugs developed with the intent of treating pain associated with fibromyalgia. Amongst these endpoints, average daily pain score (ADPS) estimated on a weekly basis has been the most frequently used as primary or co-primary endpoint in Fibromyalgia clinical programs (D. Merante, IASP 2018). Fibromyalgia is a complex pain disease characterized by peripheral and central pain augmentation. Subjects suffering from fibromyalgia are grouped into clusters (T. Giesecke, 2003) and high pain catastrophizers with high depression are highly represented (D. Goldenberg, 2008). To date pregabalin, duloxetine and milnacipran are the only approved drugs in fibromyalgia pain. They were approved by the American FDA and by the Japanese PMDA, but not by the European EMEA. Many other drugs were rejected by the regulatory agencies (sodium oxybate) or failed to provide clinical evidence of meaningful benefit in this condition (gabapentin, mirogabalin). Currently no harmonized global regulatory guidance exists in pain associated with fibromyalgia. Several global clinical development programs differed in terms of primary or co-primary endpoints utilized in such as an extremely heterogeneous population. Since the latest draft FDA Guidance on pain drug development (February 2014), average of worst daily pain (AWDP) score was recommended in pain clinical studies. We advocate the creation and harmonization of a patient-centric regulatory guidance and the use of a commonly identified primary endpoint to ultimately support the clinical development of a newly investigational medicine primarily targeting pain associated with fibromyalgia and pain-associated symptoms.

HAS THE TIME COME FOR AN HARMONIZED REGULATORY GUIDANCE FOR DEVELOPING A NEW MEDICINE TARGETING PAIN AND PAIN ASSOCIATED SYMPTOMS IN FIBROMYALGIA?