Friday, November 20, 2015

ABT-122 at the ACR 2015 Meeting in San Francisco


There has been one publication on ABT-122 at the ACR 2015 Annual Meeting in San Francisco. ABT-122 is an anti-TNF/IL-17 Dual Variable Domain immunoglobulin (DVD-Ig™). It had been "demonstrated that dual neutralization of TNF and IL-17 provides greater efficacy than blocking either cytokine alone in mouse collagen induced arthritis". But we already know, that for instance secukinumab (an anti-IL-17a MAB) did not achieve the primary endpoint (ACR20) in patients with rheumatoid arthritis. So, from the beginning I’m very sceptical. But let’s look at the study.

Roy Fleischmann and colleagues presented: “Safety, Tolerability, and Pharmacodynamics of ABT-122, a Dual TNF- and IL-17-Targeted Dual Variable Domain (DVD)-IgTM in Subjects with Rheumatoid Arthritis”. Background/Purpose: […] ABT-122 is […] is hypothesized to provide greater clinical responses in patients with RA.” Conclusion: “ABT-122 demonstrated a well tolerated safety profile in subjects with RA through 8 weeks of dosing up to 3 mg/kg, […] decreases in these chemokines [CXCL9, CXCL10, and CCL23] indicate that ABT-122 rapidly modulates potential pathophysiologic pathways in RA patients, with evidence for persistent effects after cessation of dosing. These results suggest that dual neutralization of TNF and IL-17 may provide an opportunity to control inflammation and its clinical manifestations in RA subjects and in other immune-mediated inflammatory diseases.” Thin ice!

I think the first step in convincing me would be testing ABT-122 against a TNF-inhibitor. As ABT-122 comes from AbbVie, testing against Humira shouldn’t be a problem. Until then, IL-17 in ABT-122 may be nothing more than a pinch of cinnamon in the coffee, which changes the flavour but not the caffeine content.

References:
Fleischmann R, Wagner F, Kivitz AJ, Mansikka HT, Khan N, Liu J, Gagnon J, Hong F, Ruzek M, Padley RJ. Safety, Tolerability, and Pharmacodynamics of ABT-122, a Dual TNF- and IL-17-Targeted Dual Variable Domain (DVD)-IgTM in Subjects with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/safety-tolerability-and-pharmacodynamics-of-abt-122-a-dual-tnf-and-il-17-targeted-dual-variable-domain-dvd-igtm-in-subjects-with-rheumatoid-arthritis/. Accessed November 20, 2015.


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