Saturday, May 5, 2018

The Mystery of Vobarilizumab (ALX-0061) 2nd Part


If you look for vobarilizumab at the ACR, the last publication has been at the 2014 meeting [1]. The conclusion had been: “ALX-0061 demonstrates in vitro a preferential binding profile for sIL-6R with a lesser activity for mIL-6R, while TCZ has a higher preference for mIL-6R. Preferential inhibition of sIL-6R trans-signalling by ALX-0061 could provide improved therapeutic efficacy with a better safety profile compared to TCZ.”

In 2016 AbbVie opted not to license vobarilizumab, but Ablynx wanted to seek a new partner for further development [2].

In March 2018 Ablynx announced that vobarilizumab did not meet the primary endpoint of dose response in a phase 2 study on systemic lupus erythematodes at week 24 [3]. IL-6 “induces terminal differentiation of B lymphocytes into antibody-forming cells and the differentiation of T cells into effector cells” [4] Pfizer discontinued a phase 2 study of PF-4236921 (an IL-6 inhibitor) for systemic lupus erythematosus in October 2015 [5]. But still stranger to me is the fact that tocilizumab hasn’t opted for an approval for lupus. As a matter of fact, if you search PubMed for tocilizumab in systemic lupus you’ll find about 20 studies, but none showing a move towards SLE as an indicated disease [6]. I once exploited the chance to talk to Professor Kishimoto (岸本忠三), who developed anti-IL-6 receptor therapy, but tocilizumab in SLE wasn't one of our topics. Still Ablynx tries to ride a dead horse.

I don’t see much room for vobarilizumab. I also don’t see any phase 3 study (RA) on the horizon. But let’s wait if motivation and conviction reappear as well as a sponsor for the needed phase 3 study shows up.


Links:
[1] Abstract Number: 1498; Maarten Van Roy and collaegues: ALX-0061, an Anti-IL-6R Nanobody® for use in Rheumatoid Arthritis, Demonstrates a Different in Vitro Profile As Compared to Tocilizumab - http://acrabstracts.org/abstract/alx-0061-an-anti-il-6r-nanobody-for-use-in-rheumatoid-arthritis-demonstrates-a-different-in-vitro-profile-as-compared-to-tocilizumab/
[6] Search in PubMed: "tocilizumab" [Supplementary Concept]) AND "Lupus Erythematosus, Systemic"[Mesh] https://www.ncbi.nlm.nih.gov/pubmed/?term=%22tocilizumab%22+[Supplementary+Concept]%29+AND+%22Lupus+Erythematosus%2C+Systemic%22[Mesh]


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