medwireNews: The antibody–drug conjugate ABBV-3373 has shown potential for the treatment of rheumatoid arthritis (RA) in a phase 2a proof-of-concept study.
Speaking at the EULAR 2021 Virtual Congress, Frank Buttgereit (Charité University Medicine, Berlin, Germany) explained that ABBV-3373 is composed of the tumor necrosis factor (TNF) inhibitor adalimumab linked to a glucocorticoid receptor modulator.
For the study, 144 patients with moderate-to-severe RA on background methotrexate treatment were randomly assigned to receive the antibody–drug conjugate at a dose of 100 mg given intravenously every 2 weeks (n=31), adalimumab 80 mg given subcutaneously every 2 weeks (n=17), or placebo (n=96). The average baseline DAS28-CRP in the three groups was 5.5–5.6 points.
Buttgereit explained that the primary endpoint was change in DAS28-CRP from baseline to week 12, and there were a number of prespecified comparator groups for the primary endpoint: a historic cohort of 242 patients treated with adalimumab; a group of 47 adalimumab-treated patients comprising the 17 participants given the TNF inhibitor in the trial and 30 patients from the historic cohort (combined adalimumab group); and the placebo arm from the trial.
Average DAS28-CRP decreased by 2.65 points from baseline to week 12 in the ABBV-3373 group, compared with a 2.13-point reduction in the historic adalimumab cohort, a significant difference. There was no significant difference in the mean magnitude of DAS28-CRP reduction when comparing the ABBV-3373 and combined adalimumab groups, however (2.65 vs 2.29 points). The average DAS28-CRP reduction for participants given adalimumab during the trial was 2.51 points.
The mean decrease in DAS28-CRP was 0.91 points in the placebo arm, and trial participants in both the ABBV-3373 and adalimumab groups experienced a significantly greater reduction than those given placebo.
Buttgereit added that ABBV-3373-treated patients also had a significantly greater decrease in CDAI and SDAI, and significantly higher ACR20, 50, and 70 response rates, compared with those in the historic adalimumab cohort.
He said that the antibody–drug conjugate had a safety profile that was “generally similar” to adalimumab. A total of 35.5% of ABBV-3373-treated patients experienced adverse events (AEs), as did 70.6% of trial participants given adalimumab, and the corresponding rates of serious AEs were 12.9% and 0.0%.
The four serious AEs in the ABBV-3373 group were noncardiac chest pain, pneumonia, upper respiratory tract infection, and anaphylactic shock. There were no deaths in the study.
Buttgereit concluded that the study results demonstrate the potential of ABBV-3373 “to provide improved outcomes for RA patients compared to adalimumab.”
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