Wednesday, July 1, 2020

Olokizumab at the 2020 EULAR Annual Online Meeting and a look at IL-6-Inhibitors


I've been interested in olokizumab for about decade now. In 2016 I've written: „UCB still hasn’t given up and keeps a low fire burning. I doubt that olokizumab will be approved as a drug against rheumatoid arthritis.” [1] And now, at the EULAR Meeting there are two studies. These studies concern rheumatology and not Covid-19.

Let's stay for a moment at the Covid-19 issue and the possible use of IL-6-inhibitors. In patients with dramatic infectious diseases, especially septic shock, IL-6 levels might increase 1000-fold creating cytokine storm or cytokine release syndrome. This is life threatening.

C. Zhang and colleagues published a paper [2] in which they discussed blocking IL-6 signal transduction pathway with tocilizumab, which could become an effective drug for patients with severe COVID-19.

D. McGonagle and colleagues published on the role of cytokines in Covid-19 induced pneumonia and macrophage activation syndrome-like disease [3]. They “discuss the potential impact of timing of anti-cytokine therapy on viral clearance and the impact of such therapy on intra-pulmonary macrophage activation and emergent pulmonary vascular disease.”

But back to rheumatology and the EULAR Annual Meeting. We already have tocilizumab (Actemra) and sarilumab (Kevzara), which were approved both by EMA (2009 and 2017) and FDA (2010 and 2017). So where is the niche for olokizumab? Maybe that's the reason why the development of the drug has been so slow. But maybe Covid-19 will also speed things up.

There has been a study by E. Nasonov and colleagues [4]: “OP0021 OLOKIZUMAB, MONOCLONAL ANTIBODY AGAINST IL6, IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS INADEQUATELY CONTROLLED BY METHOTREXATE: EFFICACY AND SAFETY RESULTS OF PHASE III CREDO-1 STUDY”. If you are surprised by he Russian names, don be as in July 2013 there had been an announcement by UCB: “UCB out-licenses RA drug olokizumab to Russia's R-Pharm”.Back to the study. “428 patients were randomized to OKZ 64mg q2w (n=143), OKZ 64mg q4w (n=142), and PBO (n=143).” The authors found: “Treatment with OKZ over a 24-week period was associated with significant improvements in the signs, symptoms and physical function of RA, ...” There has be a numerically higher rate of adverse events and one death due to septic shock. There were no differences between the two dosages of olokizumab in efficacy or safety outcomes.

The second study is on patient related outcomes. [5] Conclusion sny E. Nasonov and olleagues: „1. Treatment with OKZ over a 24-week period was associated with significant improvements in PRO in patients with moderate to severe RA. 2. There were no discernible differences between the two regimens of OKZ from patient’s perspective.”

Do we need another IL-6-Inhibitor? If we compare olokizumab to tocilizumab and sarilumab on the qualitativ level, there would not be need for it. If it comes to altered demand (quantitativ level), there might be need for it. But let's wait for the coming studies in rheumatology and how the world copes with Covid-19.


Links and References:
[2] Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020;55(5):105954. doi:10.1016/j.ijantimicag.2020.105954
[3] McGonagle D, Sharif K, O'Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev. 2020;19(6):102537. doi:10.1016/j.autrev.2020.102537
[4] E. Nasonov1, R. Stoilov2, T. Tyabut3, M. C. Genovese4 on behalf of Saeed Fatenejad (United States of America), Diana Krechikova, Elena Korneva,
Alexey Maslyansky, Tatiana Plaksina, Marina Stanislav, Sergey Yakushin, Elena Zonova (Russian Federation). OP0021 OLOKIZUMAB, MONOCLONAL ANTIBODY AGAINST IL6, IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS INADEQUATELY CONTROLLED BY METHOTREXATE: EFFICACY AND SAFETY RESULTS OF PHASE III CREDO-1 STUDY. DOI: 10.1136/annrheumdis-2020-eular.1688
[5] E. Nasonov1, M. Ivanova2, M. Samsonov3, T. Tyabut4, M. C. Genovese5 on behalf of Saeed Fatenejad (United States of America), Diana Krechikova, Sofia Kuzkina, Alexey Maslyansky, Tatiana Plaksina, Marina Stanislav, Sergey Yakushin, Elena Zonova (Russian Federation). THU0176 OLOKIZUMAB IMPROVES PATIENT REPORTED OUTCOMES IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS INADEQUATELY CONTROLLED BY METHOTREXATE: RESULTS FROM THE DOUBLE-BLIND, RANDOMIZED CONTROLLED PHASE III STUDY (CREDO-1). DOI: 10.1136/annrheumdis-2020-eular.2102

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