ANABOLIC EFFECT OF LNA043, A NOVEL DISEASE-MODIFYING OSTEOARTHRITIS DRUG CANDIDATE: RESULTS FROM AN IMAGING-BASED PROOF-OF-CONCEPT TRIAL IN PATIENTS WITH FOCAL ARTICULAR CARTILAGE LESIONS
Authors: S. Trattnig et al.
In this randomised, double-blind, placebo-controlled, proof-of-concept study in patients with a partial thickness cartilage lesion of the knee the chondro-regenerative capacity of multiple intra-articular (i.a.) injections of LNA043 was investigated. LNA043 is a modified, recombinant version of the human angiopoietin-like 3 (ANGPTL3) protein acting directly on cartilage-resident cells to transmit a cartilage anabolic effect. 58 patients (43 with LNA043 and 15 with Placebo) were treated with 4 weekly i.a. injections. The primary endpoint was T2 relaxation time measurement as a marker of collagen fiber network, and cartilage lesion-volume was a secondary endpoint, both using 3-Tesla MRI. Assessments were performed at baseline and weeks 8, 16, 28 and 52.
No change in T2 relaxation time was detected between treatment and PBO groups. Manual segmentation showed continuous filling of the cartilage lesions up to week 28 in LNA043-treated patients. In the medial femoral weight-bearing region, refilling was detected over time (Δ=123 mm3 at wk 28, N= 37, p= 0.05). The overall safety profile was favourable; only mild/moderate local reactions were reported, including a higher incidence of joint swelling (9.3% vs 0%) and arthralgia (11.6% vs 6.7%) for LNA043 vs PBO resolving spontaneously or with paracetamol/NSAIDs.
This proof-of-concept study shows promising results for a new compound for cartilage repair. Treatment with 4 weekly i.a. injections of 20 mg LNA043 resulted in regeneration of damaged cartilage in patients with femoral articular cartilage lesions. No sign of cartilage overgrowth was observed in healthy femoral regions. The authors mention that a phase 2b study in patients with mild to moderate knee OA is in preparation.