Novel selective cathepsin K inhibitor safely reduces bone, cartilage progression in osteoarthritis

The new selective cathepsin K inhibitor MIV-711 does not perform better than placebo in easing osteoarthritic pain, a study has shown. However, it substantially decreases bone and cartilage progression with a reassuring safety profile.

The MIV-711 showed no statistically significant changes in numerical rating scale (NRS) pain scores as compared with placebo (MIV-711 100 mg/d, –1.7; MIV-711 200 mg/d, –1.5; placebo, –1.4).

Nonetheless, its use resulted in a significant decrease in medial femoral bone area progression (p=0.002 for 100 mg/d; p=0.004 for 200 mg/d) and medial femoral cartilage thinning (p=0.023 for 100 mg/d; p=0.125 for 200 mg/d), as well as a substantial reduction in bone and cartilage biomarker levels.

Six participants experienced serious adverse events (three in the 100-mg/d group, two in the 200-mg/d group and one in the placebo group), but none of these events were treatment-related.

“This treatment may merit further evaluation as a disease-modifying osteoarthritis drug,” the authors said.

A total of 244 participants with primary knee osteoarthritis, Kellgren–Lawrence grade 2 or 3, and an nRS pain score of 4–10 were included in this 26-week randomized, double-blind, placebo-controlled phase IIa study with a 26-week open-label safety extension substudy.

Participants were randomly assigned to received MIV-700 100 (n=82) or 200 (n=81) mg daily, or matched placebo (n=77). Forty-six participants who initially received 200 mg/d and four who received placebo were given 200 mg of MIV-700 daily during the extension substudy.

The trial was limited by its relatively short duration.

“MIV-711 is a novel selective cathepsin K inhibitor with beneficial effects on bone and cartilage in preclinical osteoarthritis models,” according to the authors.