Phase II conceptual verification research succeeded! ADC drugs provide a new way to treat rheumatoid arthritis
Last Update: 2020-06-19
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On June 10, abbvie announced the positive data of the phase IIa concept study of abbv-3373 in the treatment of adult patients with moderate and severe rheumatoid arthritis (RA)< br / > < br / > abbv-3373 is an ADC composed of adalimumab and a new glucocorticoid receptor modulator (GRM), which can deliver the effective glucocorticoids directly to the activated immune cells expressing membrane bound TNF, and then regulate the TNF mediated inflammatory signaling pathwayAbbv-3373 is designed to precisely target the activated immune cells and significantly reduce the systemic side effects related to glucocorticoidsIt is intended to be developed for the treatment of rheumatoid arthritis and other immune-mediated diseases< br / > in this phase IIa, multicenter, randomized, double-blind, and positive drug control study (m16-560), 48 patients with moderate to severe RA who did not respond to methotrexate were enrolledThe safety, tolerability, pharmacokinetics and efficacy of abbv-3373 were mainly evaluated compared with the control drug HumiraThe patients were randomly divided into 2:1 groups and given abbv-3373 100mg (n = 31) or adalimumab 80mg (n = 17) once every two weeks for 12 weeks< br / > in this study, Bayesian statistical method combined with historical data was used to obtain statistical results with sufficient effectiveness at the primary end point, which was achieved by supplementing the historical data of adalimumab specified in advance and comparing and analyzing the test data of adalimumab with abbv-3373The primary end point of the study was the change of 28 C-reactive protein (das28crp) score calculated by C-reactive protein from baseline at week 12, and the statistical comparison between the two groups was specified in advanceOne is to compare the average results of abbv-3373 and adalimumab historical data, the other is to compare abbv-3373 with adalimumab combined with historical data and the data of this study< br / > the results of the first group showed that the das28crp score of the abbv-3373 group in the 12th week was - 2.65 compared with the baseline, and the average change value of the predetermined historical data of adalimumab was - 2.13, there was significant difference between the two groups (P = 0.022)The results of Bayes analysis in the second group showed that there was a 90% possibility that abbv-3373 could bring more significant improvement in DAS28 CRP score than adalimumab in the 12th week< br / > in terms of safety, abbv-3373 treatment group and adalimumab treatment group were similar, and the overall incidence of adverse events was lower (35% vs 71%)The incidence of adverse events in the two groups was more than 5%, including urinary tract infection (2 cases each), headache (2 cases each and 1 case), because the proportion of drug-related adverse events terminating treatment was 3% (1 case) and 6% (1 case), respectivelyAt week 12, 4 patients (13%) in the abbv-3373 group had serious adverse reactions, including 1 case of non cardiogenic chest pain, 1 case of anaphylactic shock (the patient has recovered completely and has no anaphylactic reaction after the end of administration), and the other two patients' serious adverse reactions (pneumonia and upper respiratory tract disease) were considered not related to the drugThe incidence of serious adverse reactions in adalimumab group was 0%< br / > in addition, the assessment of serum cortisol level at week 12 showed that abbv-3373 had no systemic glucocorticoid effect The detailed results of the study are planned to be published in a future academic conference and / or peer-reviewed journal "This proof of concept study demonstrates the clinical utility of the tnf-adc program and its potential to improve the level of care for patients with rheumatoid arthritis," said Michael Severino, vice president of abbvie Based on these results, we will continue to promote the development of tnf-adc project for the treatment of rheumatoid arthritis, and will launch clinical research in other immune-mediated diseases " < br / > abbvie has become the largest player in the RA field with Humira The biological analogues of adalimumab are now widely available in Europe and the US market will end in 2023 Abbvie has launched small molecule oral drugs (Jak1 inhibitor, on the market) and filgotinib (Jak1 inhibitor, NDA) as new forces in the field of RA, in addition to the abv-599 (Btk inhibitor) in phase II as a reserve In the field of macromolecules, Bi 655064 (CD40 McAb) and abbv-3373 (TNF ADC) are the strategic weapons of abbvie
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