Lorecivivint for knee OA unsuccessful in phase IIa trial
The novel Wnt pathway modulator lorecivivint does not appear to be effective for treating pain and inhibiting structural progression in moderate-to-severe knee osteoarthritis (OA), according to the results of a phase IIa trial.
In total, 452 patients aged 40–80 years with Kellgren/Lawrence (K/L) radiographic disease stage 2 or stage 3 OA were randomized to receive a single 2‐ml intra-articular injection of lorecivivint at 0.03 mg (n=112), 0.07 mg (n=117), or 0.23 mg (n=109) or placebo (n=114).
Of the patients who completed the study, 103 (92 percent) were on lorecivivint 0.03 mg, 107 (91.5 percent) on 0.07 mg, 95 (86.4 percent) on 0.23 mg, and 97 (83.6 percent) were on placebo. Their mean age was 60.3 years and mean body mass index 29.9 kg/m2, while 58.9 percent of the population were women.
At week 13, all groups demonstrated clinically meaningful (≥20‐point) improvements from baseline in the primary endpoint of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. The study drug did not produce significant improvements compared with placebo (mean change, −23.3 on 0.03 mg, −23.5 on 0.07 mg, −21.3 on 0.23 mg vs −22.1 on placebo; p>0.05 for all comparisons).
However, at week 52, lorecivivint 0.07 mg showed superiority over placebo in terms of WOMAC pain and function scores in the subgroups of patients with unilateral symptoms of knee OA (difference, −8.73; p=0.049 and difference, −10.26; p=0.036, respectively) and those with unilateral symptoms but without widespread pain (difference, −11.21; p=0.025 and difference, −13.38; p=0.017, respectively)
None of the treatment groups achieved a significant change in medial joint space width (JSW) at week 52 (mean change, −0.04 mm on 0.03 mg, −0.09 mm on 0.07 mg, −0.16 mm on 0.23 mg, and −0.14 mm on placebo).
The 0.07-mg lorecivivint dose likewise significantly improved medial JSW compared with placebo at week 52 among patients with unilateral symptoms of knee OA (difference, 0.39 mm; p=0.021) and those with unilateral symptoms but without widespread pain (difference, 0.42 mm; p=0.032).
Lorecivivint was safe and well tolerated.
The findings point to a target population in whom lorecivivint exerts potential efficacy, the researchers said.