Marc C. Hochberg
SAN DIEGO — The structural benefits of sprifermin, a novel recombinant human fibroblast growth factor 18, suggest it may be effective for the disease-modifying treatment of osteoarthritis, according to research presented at the American College of Rheumatology.
The presenter, Marc C. Hochberg, MD, MPH, MACP, MACR, a professor at the University of Maryland School of Medicine, in Baltimore, said the protein is, to his knowledge, the first investigational agent to prevent cartilage loss in both the lateral and medial femorotibial compartments.
“Analysis of a previous 1-year, placebo-controlled proof-of-concept phase 1b study reported statistically significant, dose-dependent effects on total and lateral cartilage thickness, in patients treated with intra-articular sprifermin injection,” Hochberg said. “Here, I present the results of 2-year primary data from a 5-year phase 2 trial, called FORWARD, which is investigating sprifermin as a potential disease-modifying drug for the treatment of knee osteoarthritis.”
According to Hochberg, researchers randomly assigned patients aged 40 to 85 years with symptomatic radiographic knee osteoarthritis, into groups intended to receive either three weekly intra-articular injections with double-blinded placebo or sprifermin administered in cycles every 6 or 12 months.
The primary endpoint was the change in total tibiofemoral joint (TFJ) cartilage thickness from baseline to year 2. The intention-to-treat population was used for non-MRI endpoints, and the modified intention-to-treat population — all intention-to-treat patients with baseline and one posttreatment MRI up to year 2 — was used for MRI endpoints.
According to the researchers, the intention-to-treat population included 549 patients with a median age of 65 years. Of these, 12.2% of those in the sprifermin group and 19.4% of those in the placebo group discontinued treatment within 2 years. There was a dose-dependent increase in total TFJ cartilage thickness, with significant differences for sprifermin 100µg at 6 and 12 months, compared with the placebo group (0.03 vs. –0.02 mm; P < 0.001, and 0.02 vs. –0.02mm; P < 0.001, respectively), the researchers found.
In addition, the researchers reported significant differences in cartilage thickness changes between sprifermin and placebo in medial and lateral TFJ compartments, and in central medial TFJ sub-regions.
“Sprifermin appears to be the first investigational medicinal product to show not only dose-dependent prevention of cartilage loss, but also an increase in cartilage thickness, not only in the TFJ, but in both the medial and lateral compartments, including the central tibiofemoral region,” Hochberg said. “These structural benefits associated with sprifermin suggest that it may be efficacious as a structure-modifying osteoarthritis drug, and present an acceptable benefit-to-risk balance in this indication.”
Hochberg M. #1L. Presented at: American College of Rheumatology Annual Meeting, Nov. 3-8, 2017; San Diego.
Disclosure: Hochberg reports professional relationships with Bioiberica SA, Bristol Myers Squibb, EMD Serono, Galapagos, IBSA SA, Eli Lilly, Novartis Pharma AG, Pfizer Inc., Plexxikon, Samumed LLC, Theralogix LLC and TissueGene.