Sunday, June 18, 2017

IL-6-Inhibitors in Rheumatoid Arthritis, where do we stand after the 2017 EULAR Annual Meeting?




Now, that we have several IL-6-inhibitors already available or shortly available, we should look, where we stand. Interleukin 6 is a cytokine relevant to many inflammatory diseases and others as well.

Tocilizumab
Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R) [1]. Tocilizumab has been approved by EMA in 2009. It is used as infusions (linear at 8 mg per kg body weight with a ceiling dosage of 800 mg) q4w or 162 mg s.c. every week.

Siltuximab
Siltuximab is a chimeric monoclonal antibody that binds to interleukin-6, so IL-6 cannot bind to soluble and membrane bound interleukin-6 receptors [2]. Siltuximab is tested for the treatment of multicentric Castleman’s disease (MCD). That is, where tocilizumab also started. Nothing at the 2017 EULAR Annual Meeting on Siltuximab.

Clazakizumab
Clazakizumab (aka ALD518 and BMS-945429) is a aglycosylated, humanized monoclonal antibody against interleukin-6 [3]. I thought of clazakizumab as a promising drug candidate, but there had been no phase 3 studies back in 2014 [4]. No new study on clazakizumab at the 2017 EULAR Annual Meeting. Last news is a phase 2b study by M.E. Weinblatt and colleagues from 2015 [5]. My guess the reason for the company’s decision is too much competition in the IL-6 niche.

Olokizumab
Olokizumab binds to interleukin-6. In 2016 I had written: “These recent studies aren’t so interesting in the results, but still there is a story being told. 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.” [6] And Adisinsight seems to back up my opinion [7]: “06 Mar 2017 Phase-III clinical trials in Rheumatoid arthritis in Lithuania (EudraCT2015-005309-35)”. But there’s no new study on clazakizumab at the 2017 EULAR Annual Meeting.

Sarilumab
I’ve just published a blogpost on sarilumab (ALX-0061) at the 2017 EULAR Annual Meeting in Madrid [8]. Sarilumab (Kevzara) received FDA approval on May 22, 2017. Sanofi and Regeneron Pharmaceuticals announced in April 2017, that the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the marketing authorization of Sarilumab (Kevzara). The dosage would be 200 mg s.c. q2w.

Sirukumab
I’ve just published a blogpost on sirukumab at the 2017 EULAR Annual Meeting in Madrid [9]. Sirukumab has been submitted for approval both to FDA and EMA during September 2016. Decisions should come soon. Or later. Sirukumab has been tested at 50 mg s.c. q4w and 100 mg s.c. q2w.

Tocilizumab Biosimilars
I haven’t seen anything on tocilizumab biosimilars at the 2017 EULAR Annual Meeting in Madrid. But the Generics and Biosimilar Initiative lists BOW070 (a tocilizumab biosimilar) by Epirus Biopharmaceuticals for the rare multicentric Castleman’s disease (MCD) [10]. LusiNEX is Taiwan based Mycenax’s biosimilar tocilizumab; LusiNEX is under process development now and is expected to initiate phase I trial in 2017 in Europe and Taiwan” [11].

So, there will be lots of competition in the relatively small IL-6 part of the tart. The reason to change from Actemra/RoActemra to a tocilizumab biosimilar, sarilumab o sirukumab will be respecting prices and reimbursements dictated by health insurance companies. Please tell me, if you see a medical reason.


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