The aim of the investigations were to determine the efficacy of intra-articularly delivered test article rhFGF18 (Sprifermin) on human chondrocytes as well as in different animal models of OA and cartilage injuries. These studies intended to determine dosing, dosing regimen and potential clinical read-outs.

Results Using human primary chondrocytes in-vitro the Mode-of-Action of Sprifermin was investigated. Different dosing regimens in-vitro demonstrated, that there is a phase of proliferation followed by a phase of differentiation with matrix synthesis.

Intra-articular administration of Sprifermin to rats, dogs, rabbits and other species demonstrated disease modifying activity in all species tested. The therapeutic effective doses ranged from 1 to 100 µg/joint i.art administered in rats and dogs/rabbits, respectively. Therapeutic efficacy was demonstrated using histology, immunhistology and imaging as read-outs.

The histopathology results indicate that Sprifermin had definite significant effects on improving the lesions of cartilage in all species tested. Anabolic effects – increased number of articular chondrocytes and formation of cartilage tissue - were seen after i.art. therapy and repair of cartilage lesion was demonstrable. The MRI data show increases in different structural measurements. s.

Conclusions The results of this study demonstrate therapeutic efficacy of Sprifermin (rhFGF18)in several read-outs and confirm previous results in pre-clinical models concerning the pharmacological effects as well as the benefit of intra-articular injections of Sprifermin for treating OA. The translational design of the studies allows a direct translation and correlation to the clinical results.

Disclosure of Interest C. Ladel Employee of: Employee of Merck KGaA