SynAct's Resomelagon Hits Key Endpoints in Phase 2b Rheumatoid Arthritis Trial, Secures US Patent Exclusivity to 2044
核心洞察
Resomelagon 40 mg combined with methotrexate achieved 76.4% ACR20 response versus 60.8% for placebo (p=0.06), reaching statistical significance in ACR/EULAR class II-III patients (76.9% vs. 56.5%, p=0.03).
The treatment produced a significant reduction in CRP (p=0.0037) and a larger SDAI reduction versus placebo (p=0.03), with no signs of immune suppression observed.
SynAct received USPTO issue notification for US patent 12,661,336 with a 742-day Patent Term Adjustment, extending exclusivity for resomelagon until July 2, 2044.
SynAct Pharma AB (搜索) reported positive results from its Phase 2b ADVANCE study showing that resomelagon, an oral selective melanocortin (搜索) agonist, combined with methotrexate produced clinically meaningful improvements in newly diagnosed, treatment-naïve patients with highly active rheumatoid arthritis (搜索) (RA). The findings, released June 15, 2026, position the first-in-class therapy for Phase 3 development and come alongside a major intellectual property milestone: the USPTO has issued notification of US patent 12,661,336 with a 742-day Patent Term Adjustment, securing exclusivity until July 2, 2044.
Efficacy Results and Statistical Significance
The ADVANCE (SynAct-CS008) study was a multicenter, randomized, double-blind, placebo-controlled, 12-week trial that enrolled 246 newly diagnosed, treatment-naïve RA patients with elevated inflammation (Clinical Disease Activity Index [CDAI] >22; DAS28-CRP >5.1; hsCRP >3 mg/L) across sites in Europe and the United States.
In the per-protocol analysis, 42 out of 55 patients (76.4%) treated with 40 mg resomelagon once daily achieved ACR20 response compared to 31 out of 51 (60.8%) in the placebo group (p=0.06). The treatment effect reached statistical significance in the subset of patients entering the study with ACR/EULAR class II-III disease: 40 out of 52 patients (76.9%) in the resomelagon 40 mg group versus 26 out of 46 (56.5%) in the placebo group (p=0.03).
ACR50 response was achieved in 21 of 55 patients (38.9%) in the resomelagon 40 mg group versus 18 of 51 (35.3%) in the placebo group. The company noted that deeper clinical responses such as ACR50 continue to improve after ACR20 saturation, suggesting that ACR50 response may increase with treatment beyond 12 weeks.
“To our knowledge, the ACR20 response for resomelagon is on par with what has been reported for the very potent Janus Kinase (JAK) inhibitors upadacitinib and baricitinib. No other compounds, except glucocorticoids have shown ACR20 response rates above 75% following 12 weeks dosing,” said Chief Scientific Officer Thomas Jonassen.
Biomarker and Disease Activity Improvements
Resomelagon at all dose levels induced statistically significant reductions in C-reactive protein (CRP). In the 40 mg group, mean CRP declined from 23.0 to 9.5 mg/L (p=0.0037), whereas the placebo group showed a non-significant change from 17.7 to 12.0 mg/L.
The Simplified Disease Activity Index (SDAI) showed a mean reduction of 35.9 in the resomelagon 40 mg group versus 28.5 in the placebo group (p=0.03). Per FDA guidance, DAS28-CRP and SDAI are considered interchangeable measures for dose-response studies.
The primary endpoint — least square mean reduction in DAS28-CRP — was 1.98 (SE 0.14) in the resomelagon group versus 1.79 (SE 0.14) in the placebo group (p=0.168). The company attributed the lack of statistical significance on this endpoint to a placebo response approximately 50% larger than observed in previous studies, rendering the primary endpoint inadequate to reach significance within the study design.
Safety Profile
The safety profile of resomelagon was described as very good, with the compound well tolerated across all dose groups. No signs of immune suppression were observed, no serious adverse events were reported in resomelagon-treated groups, and reductions in background methotrexate therapy due to lack of tolerance were reported only in the placebo control group.
Intellectual Property and Business Development
In a separate announcement, SynAct confirmed that the USPTO will issue US patent 12,661,336 on June 23, 2026, with a Patent Term Adjustment of 742 days, extending the patent’s duration to July 2, 2044.
“Securing additional patent term in the US — the world’s largest and most valuable market — is a major win for the company. It provides extended exclusivity through the anticipated peak sales period and is expected to increase the commercial potential,” said Chief Business Officer Mads Bjerregaard.
The company stated that the ADVANCE results are expected to further fuel partnering and licensing discussions. SynAct will present at the BIO International partnering conference in San Diego on June 22–25, 2026.
“The data supports a compelling profile and mechanism of action that could broaden the addressable market in RA, supporting competitive positioning across major patient groups, including those with compromised immune systems and individuals with hyperinflammatory responses to viral infections,” Bjerregaard added.
Disease Burden and Unmet Need
Rheumatoid arthritis (搜索) currently affects approximately 18 million people worldwide, a figure projected to rise to 32 million by 2050. Approximately 50% of patients present with moderate to severe disease scores at diagnosis, and major medical societies recommend progressive treatment to prevent disease progression. Resomelagon, as an add-on to first-line methotrexate therapy, may offer a safe and effective option to reduce disease symptoms and potentially delay or prevent the need for additional therapies such as glucocorticoids and biologic DMARDs.