SynAct Pharma (SYNACT) Study result summary

Study design and objectives

• Phase II-B ADVANCE study was a 12-week, randomized, double-blind, placebo-controlled trial in 246 newly diagnosed, treatment-naïve rheumatoid arthritis patients with high disease activity and systemic inflammation at sites in the U.S. and Europe.

• Patients had elevated inflammation (CRP >3 mg/L) and severe disease symptoms, starting first-line methotrexate therapy.

• Three doses of resomelagon (40, 70, 100 mg) were tested versus placebo, all with methotrexate.

• Primary endpoint was reduction in DAS28; key secondary endpoints included ACR20, ACR50, ACR70, CDAI, SDAI, and HAQ scores.

• Study had well-balanced baseline characteristics and few discontinuations.

Efficacy results

• 40 mg resomelagon group achieved ACR20 response of 76.4% vs 60.8% for placebo/methotrexate (p=0.06); significance reached in ACR/EULAR class II-III subgroup (76.9% vs 56.5%, p=0.03).

• Statistically significant reduction in CRP in all resomelagon groups; 40 mg group saw CRP drop from 23.0 to 9.5 mg/L (p=0.0037).

• SDAI reduction was greater in the 40 mg group (mean 35.9) vs placebo (28.5, p=0.03).

• ACR50 response was 38.9% in the 40 mg group vs 35.3% in placebo; deeper responses expected to improve with longer treatment.

• Primary endpoint (DAS28-CRP reduction) did not reach significance due to higher-than-expected placebo response.

Safety and tolerability

• Resomelagon was well-tolerated with few, mostly mild and transient adverse events; no serious adverse events or immune suppression reported.

• Most common side effects were transient liver enzyme increases and gastrointestinal discomfort, mainly attributed to methotrexate.

• Methotrexate dose reduction due to intolerance occurred only in the placebo group.

• No signs of immunosuppression or increased infection rates; safety profile supports early use before immunosuppressive therapies.