Sprifermin is a recombinant human fibroblast growth factor 18 (rhFGF18), currently under investigation as a potential therapeutic agent for osteoarthritis. It aims to address underlying structural damage in affected joints, primarily focusing on cartilage health and repair.
How Sprifermin Works
Sprifermin mimics the natural biological role of fibroblast growth factor 18 (FGF18), which helps maintain cartilage health and facilitate its repair. FGF18 activates fibroblast growth factor receptor 3 (FGFR3) on chondrocytes, the cells that produce and maintain cartilage. This activation stimulates chondrocyte proliferation.
Beyond cell growth, sprifermin also promotes the synthesis of the extracellular matrix (ECM), the structural framework of cartilage. This includes increasing the production of proteoglycans and type II collagen. Preclinical studies confirm sprifermin’s role in promoting hyaline cartilage and ECM synthesis, contributing to cartilage repair. The drug also inhibits the activity of proteolytic enzymes, such as MMP-13 and ADAMTS-5, which are known to degrade cartilage.
Sprifermin’s Role in Osteoarthritis Treatment
Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive breakdown of articular cartilage. Current treatments for OA largely focus on managing symptoms like pain and stiffness, but they do not typically address the underlying structural damage or slow the disease’s progression. This leaves a significant unmet need for therapies that can modify the disease course.
Sprifermin is being developed as a disease-modifying osteoarthritis drug (DMOAD), a class of treatments designed to directly target cartilage repair and regeneration. By stimulating chondrocyte proliferation and ECM synthesis, sprifermin aims to rebuild or restore damaged cartilage, offering a potential solution to slow or even reverse disease progression. This regenerative approach could move beyond symptom management, offering a way to improve joint structure and function over time.
Clinical Trial Outcomes and Safety Profile
The FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) study (NCT01919164) is a clinical trial that evaluated sprifermin’s efficacy and safety in knee OA patients. In this 5-year, dose-finding trial, participants received intra-articular injections of sprifermin at doses of 30 µg or 100 µg every 6 or 12 months, or a placebo, for 18 months. The primary analysis at two years focused on changes in total femorotibial joint cartilage thickness, measured by quantitative magnetic resonance imaging (qMRI).
The FORWARD study showed a statistically significant, dose-dependent increase in total femorotibial joint cartilage thickness with sprifermin. The 100 µg dose administered every 6 months resulted in a mean increase of approximately 0.05 mm compared to placebo at year two. This structural benefit was maintained up to year five, indicating a sustained effect on articular cartilage modification for at least 3.5 years post-treatment. Pain scores generally improved by about 50% from baseline in all groups, including placebo. However, a subgroup of patients at risk of progression showed sustained, clinically meaningful pain improvement with sprifermin compared to placebo by year three, lasting through year five.
Regarding safety, sprifermin was generally well-tolerated in the FORWARD study. Adverse events were reported by 96%–98% of patients receiving sprifermin and 98% of those on placebo, with most being mild or moderate and considered unrelated to the treatment. Less than 10% of study withdrawals were due to adverse events. The most common treatment-emergent adverse event reported was arthralgia.
No patients in the 100 µg every 6 months group underwent knee replacement during the five-year follow-up period. Sprifermin is typically administered via intra-articular injection, directly into the affected joint.