Rottapharm Biotech: POC in osteoarthritis pain

Results of the proof-of-concept trial suggest the selective imidazoline-2 (I2) receptor agonist CR4056 could be an alternative to the side-effect-prone opioid analgesics in the treatment of osteoarthritis pain. According to the the study, which assessed efficacy using the WOMAC pain score (0–100 scale) compared to placebo, CR4056 performed particularly and significantly well in male patients phenotyped to belong to the metabolic osteoarthritis phenotype.

After 14 days of treatment with the small molecule I2 receptor ligand, median WOMAC pain improvements were 10 points on placebo and 14, 20 and 16 in women, men, and pooled CR4056 groups (P = 0.184, 0.030 and 0.070 vs placebo, respectively). Pre-specified subgroup analysis in the metabolic osteoarthritis phenotype (BMI ≥ 27.5 kg/m², N = 156) showed statistically significant differences in all CR4056-treated groups vs placebo of 12–18 points.

According to Lucio Rovati, Chief Scientific Officer at Rottapharm Biotech, "it is indeed possible that a single magic bullet, suitable for all osteoarthritis patients, does not exist and we will have to use drugs that are different for each phenotype. The metabolic OA phenotype is very common and occurs when there is a disruption of metabolic activities in the body, which may lead to obesity," he added. "CR4056 appears to be particularly effective on pain characterizing the metabolic osteoarthritis phenotype: we want to pursue this specific signal in Phase III and we are discussing potential partnerships in this regard.”

Preclinically, CR4056 emerged as one of the most effective non-opioid analgesics ever described. Growing evidence on the functions of I2 receptors demonstrates that I2 ligands facilitate the noradrenergic inhibitory pain pathways through a new, allosteric molecular mechanism.

Rottapharm Biotech, which is focussed on rheumatic diseases such as osteoarthritis and rheumatoid arthritis (RA), suggests that potential therapeutic indications might span from nociceptive
to neuropathic pain.  The company was spun-off in 2014 from the former R&D division of Rottapharm|Madaus, of which it retained the whole capabilities, infrastructures, and innovative drug discovery programmes and assets.