medwireNews: Results of the phase II FORWARD trial suggest that sprifermin, an investigational recombinant human fibroblast growth factor, may prevent cartilage loss in patients with knee osteoarthritis (OA), but its effect on pain and physical function remains unclear.
Presenting the results at the 2017 ACR/ARHP Annual Meeting in San Diego, California, USA, Marc Hochberg (University of Maryland School of Medicine, Baltimore, USA) explained that sprifermin “induces hyaline cartilage formation in vitro by increasing chondrocyte proliferation, resulting in increased overall extracellular matrix production.”
The FORWARD investigators randomly assigned patients with symptomatic knee OA to receive four cycles of sprifermin 30 µg or 100 µg given as intra-articular injections once weekly for three consecutive weeks, or to receive placebo. Patients were given treatment cycles at 6- or 12-monthly intervals.
Patients receiving sprifermin experienced a dose-dependent increase in total tibiofemoral joint cartilage thickness from baseline to the 2-year follow-up. The 110 patients in the sprifermin 100 µg every 6 months group and the 110 in the 100 µg every 12 months group had significantly greater increases in cartilage thickness than the 108 placebo-treated patients, with corresponding mean increases of 0.03 mm and 0.02 mm versus a decrease of 0.02 mm. Although patients in the 30 µg groups experienced improvements in cartilage thickness compared with those in the placebo group, this difference did not reach statistical significance.
Hochberg and colleagues also observed a dose-dependent increase in medial and lateral tibiofemoral cartilage thickness among sprifermin-treated patients.
“Sprifermin appears to be the first investigational medicinal product to show dose-dependent prevention of cartilage loss and an increase in cartilage thickness,” said Hochberg.
However, there was no significant difference between the groups in pain, stiffness, and physical function, as measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) over the study period, with participants in all five groups experiencing around a 50% improvement in WOMAC scores.
Speaking from the audience, Roy Fleischmann (University of Texas Southwestern Medical Center, Dallas, USA) asked whether the improvements in cartilage thickness were clinically relevant given the lack of difference in pain scores between the groups.
Hochberg argued that the change in cartilage thickness observed between the 100 µg and placebo groups is comparable to the cutoff value for predicting whether patients will undergo total knee arthroplasty, and explained that “there was no regulation in the medications that individuals could take” during the trial, which could have confounded the results.
“Analyses are […] in progress to investigate the usage of pain medications during the course of the trial,” and patients will be followed up for 5 years to assess whether sprifermin has a delayed effect on pain, he added.
In the safety analyses, the team observed comparable rates of serious and treatment-emergent adverse events (TEAEs) among patients in the sprifermin and placebo groups. The most commonly reported TEAEs were musculoskeletal and connective tissue disorders.
Taken together, these findings suggest that sprifermin “may be efficacious as a structural and disease-modifying OA drug, which presents an acceptable benefit-risk balance in this indication,” concluded Hochberg.
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