• The Data Safety Monitoring Board (DSMB) finds no safety concerns in the 50 mg and 100 mg dose cohorts
  • Signs of efficacy against rheumatoid arthritis was observed. Thus, the number of patients changing from the severe to the moderate Clinical Disease Activity Index (CDAI) score was higher than placebo in both treatment groups in a dose dependent manner
  • The DSMB recommends that the study continues to Part 2 in which the patients are randomized to 50 mg AP1189, 100 mg AP1189 and placebo plus methotrexate (MTX)
  • Full Phase 2 topline data is expected by the end of Q2 2021

LUND, Sweden I November 9, 2020 I SynAct Pharma AB (“SynAct”), a clinical stage biopharmaceutical company developing novel therapies of inflammatory diseases, today announced that an independent Data Safety Monitoring Board (DSMB) has reviewed unblinded and validated data from part 1 of the company’s Phase 2a study in patients with rheumatoid arthritis (RA) with high disease activity with the aim to recommend which dose(s) of AP1189 to be brought into part 2 of the study. The DSMB is composed of independent clinical experts and has the responsibility to recommend further dosing and continuation of the study. The company remains blinded to the data.

“We are very excited that DSMB observes good safety and promising signals of efficacy in the interim analysis of AP1189 in patients with severe and newly diagnosed rheumatoid arthritis. This may indicate that we might see a clinical effect already following 4 weeks of treatment. We look forward to initiate recruitment in part 2 of the study this week. As we are testing newly diagnosed patients, we have decided to name this study BEGIN,” said Thomas Jonassen, MD, CSO at SynAct Pharma AB.

The BEGIN study is designed as a placebo-controlled double-blind multicenter study with a 2:1 randomization ratio of once-daily dosing of AP1189 vs placebo in RA patients referred to rheumatological departments due to uncontrolled disease activity defined as a Clinical Disease Activity Index (CDAI) score higher than 22. AP1189 or placebo is dosed once daily for 4 weeks in parallel with the initiation of a treatment with the disease-modulating, anti-rheumatic drug methotrexate (MTX). The full study consisting of part 1 and 2 will include up to 90 patients. The second part of the study will be initiated this week according to the DSMB recommendation.

The data analysis conducted on the first 26 patients who has completed treatment indicates that AP1189 is safe and well tolerated at the current dose schedule. There are no reports of any serious adverse events. The overall frequency of adverse events is similar in the two treatment groups, and slightly higher than the placebo group. The most common adverse event was nausea.

The median CDAI at the point of inclusion in the study was 34 (low: 23; high: 49). The fraction of patients that had a reduction in CDAI to 22 or lower upon 4 weeks of therapy, i e going from severe to moderate or low disease activity, was as follows:

Placebo + MTX AP1189 50 mg + MTX AP1189 100 mg + MTX
44% 67% 75%

Based on these findings the DSMB concludes the following:

“The efficacy data indicated an effect of AP1189 on rheumatoid arthritis which was larger than placebo (may also be dose-dependent), the number of patients going from severe to moderate CDAI score was higher in both treatment groups than in the placebo group. However, the small number of patients precluded any statistical evaluation of significant differences.”

Based on the interim analysis, the DSMB recommend continuing into part 2 of the BEGIN study with AP1189 dosed at either 50 mg, or 100 mg as well as a placebo group, and in all three groups MTX in a 1:1:1 randomization according to the protocol.

SOURCE: SynAct Pharma