ABBV-3373, a novel antibody drug conjugate (ADC) for the treatment of rheumatoid arthritis, demonstrated similar efficacy to adalimumab at 12 weeks in a randomized, double-blind, placebo-controlled phase 2a trial. The results were published in Arthritis & Rheumatology.
The novel ADC is created through linking the anti-tumor necrosis factor (TNF) monoclonal antibody adalimumab to a glucocorticoid receptor modulator (GRM). In this trial, the efficacy and safety of ABBV-3373 was compared with adalimumab alone in patient with moderate to severe rheumatoid arthritis with background methotrexate therapy.
Forty-eight patients from 14 sites were randomized to receive either 100 mg of intravenous (IV) ABBV-3373 (n=31) followed by subcutaneous placebo or 80 mg of subcutaneous adalimumab (n=17) followed by IV placebo, administered every other week. In total, 46 patients completed 12 weeks of study treatment, and 41 patients completed 24 weeks.
The primary endpoint for the experimental group was change from baseline in the clinical disease activity index (CDAI), simplified disease activity index (SDAI), and 28-joint disease activity score using erythrocyte sedimentation rate (DAS28[ESR]).
The ABBV-3373 arm demonstrated superiority in change from baseline in DAS28(ESR) at week 12 compared with a historical adalimumab reference value (-2.65 vs. -2.13, respectively; P=.022). ABBV-3373 also led to a numerically greater improvement in DAS28(CRP) than in-trial adalimumab (-2.51). Both treatment arms demonstrated superiority compared with synthetic placebo (P<.001).
Overall reductions in DAS28(CRP) were similar between patients in both treatment arms and were maintained through week 24. The authors reported that 70.6% of patients treated with ABBV-3373 that achieved DAS28(CRP) ≤3.2 at week 12 maintained this response at week 24, despite the switch to a placebo at week 11.
Regarding safety outcomes, the safety profile of ABBV-3373 was similar to in-trial adalimumab. During the initial 12 weeks of treatment, the overall rate of treatment-emergent adverse events (AEs) was lower with the use of ABBV-3373 (35.5% vs. 70.6%, respectively). Two patients from each treatment arm discontinued treatment following an AE.
Four serious AEs occurred with ABBV-3373: Non-cardiac chest pain, pneumonia, upper respiratory tract infection, and anaphylactic shock. The authors noted that the two serious infections were moderate, resolving within 9 to 12 days, and considered to be unrelated to the study drug. The case of anaphylactic shock was reported following IV administration on day 29, after which use of the study drug was permanently discontinued. “The event was determined to have a reasonable possibility of relationship to ABBV-3373,” the authors wrote. “After increasing IV administration from 3 minutes to 15 to 30 minutes, no similar events were reported.”
In summary, the authors wrote, “Data from this proof-of-concept trial support the continued development of a TNF-GRM-ADC for the treatment of rheumatoid arthritis, with the potential to achieve superior outcomes compared to currently available therapies.” They noted that a subcutaneous derivative of ABBV-3373 is currently in development for polymyalgia rheumatica.