AbbVie recently released new data from a phase IIa study (M16-560) of ABBV-3373 in the treatment of adults with moderate to severe rheumatoid arthritis (RA). ABBV-3373 is a novel antibody drug conjugate (ADC) consisting of anti-tumor necrosis factor antibody adalimumab and glucocorticoid receptor modulator (GRM). The new data released this time shows that ABBV-3373 has effectively reduced disease activity while showing no systemic glucocorticoid effect.
It is worth mentioning that this is the first result report of a new ADC in the treatment of RA. The full results of this Phase IIa study will be announced at an upcoming medical conference and will be published in a peer-reviewed journal.
ABBV-3373 is a research ADC developed by AbbVie. It is connected to adalimumab by a new type of glucocorticoid receptor modulator (GRM). Directly delivered to activated immune cells expressing membrane-bound tumor necrosis factor (TNF) to regulate TNF-mediated inflammation pathways. This ADC is designed to accurately target activated immune cells while significantly inhibiting inflammation and reducing systemic side effects associated with glucocorticoids. ABBV-3373 is a research drug that has not been approved by regulatory agencies and is currently being studied for the treatment of rheumatoid arthritis (RA) and other immune-mediated diseases.
RA-rheumatoid arthritis (Image source: rheumatologyadvisor.com)
The M16-560 study is a phase 2a, multicenter, randomized, double-blind, double-simulation, positive drug-controlled study in moderate to severe rheumatoid arthritis (RA) with insufficient response to methotrexate (MTX) It is carried out in adult patients and aims to evaluate the safety, tolerability, pharmacokinetics and efficacy of ABBV-3373. In the study, patients were randomly assigned in a 2:1 ratio and received ABBV-3373 (n=31, dose 100 mg, every other week [EOW]) or adalimumab (n=17, dose 80 mg, EOW), for treatment 12 weeks.
In this proof-of-concept study, Bayesian statistical methods with historical data were used to obtain sufficient statistical power. This was accomplished by using the historical data of adalimumab to supplement the pre-designated adalimumab data in the trial. , Compared with ABBV-3373 for primary endpoint analysis. These historical data were obtained from three adalimumab trials in a similar treatment environment. The primary endpoint was the change in 28 C-reactive protein (DAS28-CRP) from the baseline examination to the 12th week disease activity score, and two statistical comparisons were pre-designated. The first item compares the average results of ABBV-3373 and historical adalimumab data, and the success criterion is a two-sided p-value ≤0.1. The second item compares ABBV-3373 with the combined trial and historical adalimumab data (success criterion: probability> 95%).
The results of the first statistical comparison showed that compared with the pre-specified historical average value of adalimumab (-2.13), the ABBV-3373 treatment group had a greater difference in the DAS28-CRP change from baseline to the 12th week primary endpoint (-2.65 , P=0.022). The second statistical comparison based on Bayesian analysis shows that the probability that ABBV-3373 is associated with a greater improvement in DAS28-CRP from baseline to week 12 compared to adalimumab combining test data and historical data is 90%. In addition, evaluation of serum cortisol levels during 12 weeks of treatment showed that ABBV-3373 did not exhibit systemic glucocorticoid effects.
In the trial, the safety of ABBV-3373 was generally similar to that of adalimumab. The overall adverse event (AE) incidence rate of ABBV-3373 is lower than that of adalimumab (respectively: 35%[n=11] vs 71%[n=12]). AEs occurring in ≥5% of patients were urinary tract infections, with 2 events in the ABBV-3373 group and 1 event in the adalimumab group. 6% (n=1) of the adalimumab group and 3% (n=1) of the ABBV-3373 group discontinued treatment due to adverse events. During 12 weeks of treatment, 4 patients (13% [n=4]) in the ABBV-3373 group had serious adverse events (SAE), and 0 patients (0% [n
=0]). In the ABBV-3373 group, 2 SAEs (pneumonia and upper respiratory tract disease) were considered unrelated to the study drug. One SAE was non-cardiogenic chest pain, and one SAE was reported as anaphylactic shock. The patient had fully recovered. No further allergic events were reported after prolonged administration in patients who were subsequently administered.
Michael Severino, MD, Vice Chairman and President of AbbVie, said: "This proof-of-concept study demonstrates the clinical activity of the TNF-ADC platform and its potential to improve the standard of care for patients with rheumatoid arthritis. Based on these results, we will advance rheumatoid joints The development of TNF-ADC platform in Yanzhong and began clinical research in other immune-mediated diseases."