Wnt Pathway Inhibition Alleviates Symptoms of Knee Osteoarthritis
"Radiographic and clinical outcomes suggested SM04690 has potential as a [disease-modifying osteoarthritis drug] for knee [osteoarthritis] treatment."
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SAN DIEGO — Inhibition of the Wnt pathway with the small molecule SM04690 was shown to improve pain and maintain or improve radiographic outcomes in patients with knee osteoarthritis, in a study presented at the 2017 2017 ACR/ARHP Annual Meeting, held November 3-8., held November 3-8.
In this phase 2 clinical trial, 455 adults with Kellgren-Lawrence grades 2 to 3 knee osteoarthritis were randomly assigned to receive a single injection of 0.03 mg SM04690, 0.07 mg SM04690, 0.23 mg SM04690, or placebo in the most painful knee. Pain and function were assessed with the Western Ontario and McMaster Universities Arthritis Index Outcome scales over a 52-week period, and medial joint space width was evaluated on radiographs through 52 weeks.
Clinically meaningful improvements (>10% full range) in outcomes relative to baseline were reported in all groups as early as 4 weeks. In a subgroup analysis of patients with unilateral symptoms, improvements in pain scores (P =.049) and clinically meaningful improvements in function scores (P =.035) relative to placebo were reported in patients receiving 0.07 mg SM04690.
In patients with unilateral symptoms and no widespread pain, clinically meaningful improvements in pain and function were reported at week 26 (P =.039 and .027 for pain and function, respectively), week 39 (P =.042 and .035), and week 52 (P =.025 and P =.017) for patients receiving 0.07 mg SM04690 vs placebo. At 52 weeks, nonsignificant improvements in mean joint space width were noted relative to placebo (–0.14 mm) for patients in the 0.03-mg SM04690 (0.10 mm), 0.07-mg SM04690 (0.06 mm), and 0.23-mg SM04690 (–0.02 mm) groups. No serious treatment-related adverse events were reported.
The study investigators concluded that "radiographic and clinical outcomes suggested SM04690 has potential as a [disease-modifying osteoarthritis drug] for knee [osteoarthritis] treatment."
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Yazici Y, McAlindon TE, Gibofsky A, et al. Results from a 52 week randomized, double-b, placebo-controlled, phase 2 study of a novel, intra-articular, Wnt pathway inhibitor (SM04690) for the treatment of knee osteoarthritis. Presented at: 2017 ACR/ARHP Annual Meeting; November 3-8, 2017; San Diego, California. Poster 935.