Sprifermin Shows ‘Positive Sign’ for Cartilage Thickness in Knee OA
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Patients with knee osteoarthritis who received a high sprifermin dose of 100 g administered every 6 or 12 months, demonstrated significantly improved total femorotibial joint cartilage thickness after 2 years, although it remains unclear whether these findings are clinically important, according to phase 2 data published in JAMA.
“In a dose-ascending phase 1 study, sprifermin showed no measurable systemic effects or safety concerns in patients with osteoarthritis scheduled for total knee replacement, and there were no safety concerns in a 1-year phase 1b proof-of-concept study,” Marc C. Hochberg, MD, MPH, of the University of Maryland School of Medicine, in Baltimore, and colleagues wrote. “The latter showed statistically significant dose-dependent effects on total and lateral compartment cartilage thickness in patients receiving 100 g of sprifermin vs. placebo, but failed to meet its primary end point of change from baseline in central medial femorotibial compartment cartilage thickness.”
To analyze the effect of sprifermin, a novel recombinant human fibroblast growth factor 18, on total femorotibial joint cartilage thickness among patients with symptomatic knee OA, Hochberg and colleagues the phase-2 FORWARD study, a 5-year, dose-finding, multicenter randomized clinical trial. The researchers recruited adults aged 40 to 85 years with symptomatic, radiographic knee OA and a Kellgren-Lawrence grade of 2 or 3, with enrollment stretching from July 2013 to May 2014. The final participant visit occurred in May 2017.
The participants were randomly assigned to one of five treatment groups. A total of 110 patients were given intra-articular sprifermin injections of 100 g every 6 months. Another 110 were administered the same dose every 12 months. Another 111 participants were administered 30 g of sprifermin every 6 months, and 110 were given 30 g every 12 months. The placebo group included 108 participants. All treatments included weekly injections during a period of 3 weeks.
The primary endpoint was the change in total femorotibial joint cartilage thickness, as measured by MRI, at 2 years. There were 15 secondary endpoints, including 2-year change in WOMAC scores. A total of 549 participants completed the 2-year follow-up. The researchers also reported a 3-year follow-up analysis.
According to the researchers, changes from baseline to 2 years in total femorotibial joint cartilage thickness were 0.05 mm (95% CI, 0.03-0.07) for patients treated with 100 g of sprifermin administered every 6 months, compared with placebo. Changes demonstrated in the other groups, compared with placebo were 0.04 mm (95% CI, 0.02-0.06) for 100 g of sprifermin every 12 months; 0.02 mm (95% CI, –0.01 to 0.04) for 30 g of sprifermin every 6 months; and 0.01 mm (95% CI, –0.01 to 0.03 mm) for 30 g of sprifermin every 12 months.
There were no statistically significant differences in mean absolute change from baseline in total WOMAC scores for any sprifermin group, compared with placebo.
Regarding safety, the most frequently reported adverse event was arthralgia, which was seen in 43% of patients in the placebo group; in 41.3% of those treated with 100 g of sprifermin every 6 months; 45% of those given 100 g of sprifermin every 12 months; in 36% of those who received 30 g every 6 months; and in 44% of those treated with 30 g every 12 months.
“While the increase in cartilage thickness is a positive sign, we do not know at this point whether it has any clinical significance,” Hochberg said in a press release. “It is not known whether those who experience increased cartilage thickness over time will be able to avoid or delay knee replacement surgery.”
According to the press release, the researchers more recently performed a post-hoc analysis of the data, specifically focusing on patients with OA, severe pain and narrow joint space, as well as a higher risk for disease progression. In this analysis, participants treated with 100 g of sprifermin every 6 months demonstrated significant improvements in arthritis symptoms 18 months following their last injection, compared with placebo.
“These results support further investigation of sprifermin as a potential osteoarthritis treatment for both structure medication and symptom relief for higher-risk patient populations,” Hochberg said in the release. – by Jason Laday
Disclosure: Hochberg reports being the president of Rheumcon Inc., as well as consulting fees from Bioiberica SA, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Galapagos, IBSA Biotechniq SA, Novartis Pharma AG, Pfizer, Plexxikon, Samumed LLC, Theralogix LLC, and TissueGene Inc. Please see the study for all other authors’ relevant financial disclosures.
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