SynAct Pharma announces top line data from the 12-week EXPAND P2b clinical trial in severely active newly diagnosed rheumatoid arthritis patients

  • Resomelagon (AP1189) did not meet the primary endpoint of a statistically higher rate of 20% improvement in the American College of Rheumatology score (ACR20) versus placebo at 12 weeks
  • The safety profile of resomelagon continued to be favorable with no meaningful differences in adverse events seen between active and placebo groups
  • Subjective measures used in ACR scoring were out of line with expectations and appeared to contribute to a much higher than expected placebo response rate and in difficulty in discerning between active and placebo groups
  • Objective measures were more in-line with expectations based upon the positive BEGIN P2a
  • SynAct will continue to assess these topline data as well as the full study data set to better understand these results
  • SynAct will host an investor webcast to discuss the EXPAND top-line results

SynAct Pharma AB (Nasdaq Stockholm: SYNACT), a clinical stage biotechnology company focused on the resolution of inflammation through the selective activation of the melanocortin system, today reported topline results from the 12-week P2b EXPAND study of 100mg once-daily oral resomelagon (AP1189) in newly diagnosed rheumatoid arthritis (RA) patients experiencing severe disease activity. The study did not meet its primary endpoint of significance over placebo with the ACR20 outcome. Although resomelagon did not demonstrate a clear clinical benefit on the primary endpoint it continued to demonstrate a favorable safety profile. Objectives measures of activity in the EXPAND trial were more in-line with the BEGIN study. SynAct management will hold a webcast to discuss this announcement later today (details below).

The EXPAND (SynAct-CS007) study was a multicenter, randomized, double-blind, placebo-controlled, 12-week study in newly diagnosed, treatment naïve patients with highly active RA (Clinical Disease Activity Score (CDAI) > 22) conducted in sites in Bulgaria and Moldova. 127 patients presenting with high disease activity (CDAI > 22) were randomized 1:1 for treatment with once daily 100 mg resomelagon or placebo added to a background of methotrexate (MTX) therapy. 54.7% of patients treated with 100mg of once-daily oral resomelagon achieved an ACR20 response at 12-weeks as compared to 55.7% of patients receiving placebo. This unexpected finding in part was driven by high placebo responses linked to the subjective component measures of the ACR scoring system. SynAct continues to assess this top-line study data to better understand these results.

Resomelagon continued to demonstrate a favorable safety profile in this high activity patient population. The overall rate of treatment emergent serious adverse events (SAEs) was 1.6% (n=2), with 1 SAE in each group. The overall rate of patients experiencing treatment emergent adverse events (AEs) was 44.4% and 42.2% for resomelagon and placebo treated patients respectively (all patients received MTX). There were no observed signs of immunosuppression seen in the resomelagon group over that associated with background methotrexate therapy.

“We were surprised by the unexpected subjective measure responses seen in the EXPAND study which contributed to the very high placebo response and the difficulty in showing a clear benefit of resomelagon over placebo in patients with background methotrexate therapy. The EXPAND study was based upon the successful BEGIN P2a study where resomelagon demonstrated significant results over placebo on the ACR20 and in the mean change in CDAI outcomes at 4-weeks,” stated Thomas Jonassen, CSO of SynAct Pharma. “Objective measures in the EXPAND study like improvements in the number of tender and swollen joint counts were more in line with expectations. We continue to assess the topline data as well as additional data coming from the trial to better understand these results. Importantly, with the ongoing RESOLVE study, we are studying resomelagon in patients who have moderate to severely active disease despite having an adequate course of methotrexate and we also have experienced sites in the US who have recruited well in the study.”

“While we are disappointed in the EXPAND topline results, we remain steadfast in our belief in the potential for resolution therapy with resomelagon to help address key unmet needs not fully addressed with current treatments. The treatment naïve population studied in both the BEGIN and EXPAND studies has a high-level of unmet need, but the DMARD incomplete responder patients being studied in the RESOLVE study represent the real high-value commercial opportunity for resomelagon in RA,” said Torbjørn Bjerke, CEO of SynAct Pharma. “The DMARD-IR patients in the RESOLVE study have failed MTX therapy and represent a significant population of patients with high unmet need and a clear commercial potential. Our belief in the potential of resomelagon remains undeterred. We eagerly await the results of the P2a portion of the RESOLVE study in October.”

Investor webcast Information – September 4th, 2023, 15:00 (Europe/Stockholm)
Dial-in number to the teleconference will be received by registering on the link below. After the registration you will be provided phone numbers and a conference/user ID to access the conference.

For further information, please contact:
Torbjørn Bjerke
CEO, SynAct Pharma AB
Phone: +46 727 44 41 58
Email: [email protected]
Email: [email protected]

Thomas Jonassen
CSO, SynAct Pharma AB
Phone: +45 40 15 66 69
Email: [email protected]

About SynAct Pharma AB
SynAct Pharma AB (Nasdaq Stockholm: SYNACT) is a clinical stage biotechnology company focused on the resolution of inflammation through the selective activation of the melanocortin system. The company has a broad portfolio of oral and injectable selective melanocortin agonists aimed at inducing anti-inflammatory and inflammation resolution activity in autoimmune and inflammatory diseases to help patients achieve immune balance and overcome their inflammation. For more information:

About resomelagon (AP1189) 
Resomelagon (AP1189), is a once-daily oral selective melanocortin agonist that selectively activates melanocortin receptors 1 and 3 that are directly involved in inflammation and its resolution. These receptors are located on immune cell types including macrophages and neutrophils. 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).

The EXPAND (SynAct-CS007) study is a multicenter, randomized, double-blind, placebo-controlled, 12-week study in newly diagnosed, treatment naïve patients with highly active RA (Clinical Disease Activity Score (CDAI) > 22) In EXPAND, 127 RA patients with high disease activity (CDAI > 22) were randomized 1:1 for treatment with either 100 mg resomelagon (AP1189) tablets or placebo tablets for a once daily dose for 12 weeks, concurrently with the initiation of dosing with methotrexate. The primary efficacy read-out in the EXPAND is proportion of patients achieving 20% improvement in ACR (ACR20) at week 12 relative to placebo. The safety evaluation included adverse event monitoring, biochemical and hematological evaluation, physical examinations, and vital sign measurements. In addition, several secondary efficacy endpoints are defined, including, ACR50, ACR70, CDAI, and Disease activity score 28 (DAS-28) change over time, Change in Health Assessment Questionnaire – Disability Index (HAQ-DI) and Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue), as well as use of corticosteroids as rescue medication. Tertiary endpoints are included to further explore the effect of resomelagon (AP1189) on biomarkers and by evaluation of synovial inflammation using magnetic resonance imaging (MRI).