SynAct Pharma AB reported additional results from the 12-week Phase 2b EXPAND study of 100mg once-daily oral resomelagon (AP1189) in newly diagnosed rheumatoid arthritis (RA) patients experiencing severe disease activity. SynAct previously announced that while the overall study did not achieve its primary endpoint, resomelagon treatment demonstrated consistent efficacy and activity over placebo in patients with elevated CRP levels (>3mg/L) at baseline as evidenced by a 70.6% ACR20 response rate at 12 weeks vs 54.3% in the placebo group. Today's release adds more detailed data on the HAQ disability index, data from the sub-study of MRI imaging of wrist and hand joints and biomarker data all supporting resomelagon efficacy and activity in this important and relevant patient population.

SynAct previously announced that in patients with baseline CRP >3mg/L at baseline treated with resomelagon had an average decrease in their HAQ-DI score of 0.64 which is almost 3 times the minimal clinically important difference (MCID). release indicates that the HAQ-DI sections showing the largest mean disability improvements over placebo relate to improvements in hand strength and dexterity. Resomelagon treated patients reported a 50% improvement in activates relating to eating, 43% in dressing and grooming and 38% in grip as compared to 24%, 25% and 18% respectively for placebo.

A sub study using contrast-enhanced MRI to assess joint inflammation in patients with inflamed wrist and hand joints was conducted in 23 patients treated with placebo. 74% of the resomelagon patients had CRP>3 mg/L at baseline compared to 33% in the placebo group. The MRI techniques used measure the peak enhancement and rate of enhancement of a contrast agent as indicators of synovial inflammation.

Comparing the 12 weeks MRI with the Baseline MRI the resomelagon group showed a larger reduction in both mean peak enhancement (3.8 ml vs 1.2 ml) and mean initial rate of enhancement (0.06 ml/sec vs 0.01 ml/sec) indicating a greater reduction in inflammation intensity. Activation of these receptors can result in both anti-inflammatory effects like lowering the level of pro-inflammatory molecules and in pro-resolution effects like switching macrophages to perform inflammation 'clean-up', known as efferocytosis (J Immun 2015, 194: 3381-3388). This dual effect has shown to be effective in disease models of inflammatory and autoimmune diseases and the clinical potential of the approach is currently tested in clinical programs in patients with rheumatoid arthritis (ra).