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Clinical Decision Making: Evaluating Biologics in Lupus Management - Episode 12

Novel Treatments Under Investigation for Lupus Treatment

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Experts in rheumatology provide an overview of novel treatment options currently under investigation for the treatment of systemic lupus erythematosus and lupus nephritis.

Kristi V. Mizelle, MD, MPH, FACR: There’s several different agents that have been tried, of course as far as biologics are concerned, and then also some small molecules. We have belimumab and anifrolumab, which have been FDA approved for Systemic lupus erythematosus, and belimumab has been approved for Lupus Nephritis. There are some other drugs that are in the pipeline that are also biologics, and I believe one is a small molecule. Obinutuzumab, it’s in a phase 3 study right now with Dr Furie [Richard Alan Furie, MD] being one of the lead authors on lead on that study, and it’s called ALLEGORY. And that’s a type 2 anti-CD20 monoclonal antibody, and that differs from rituximab which was a type 1 anti-CD20 monoclonal antibody. And that’s looking to see if you could get lupus nephritis under control using that. Previous trials looking at rituximab for lupus nephritis were not successful, and the thought is that maybe it’s the part of the CD20 that the monoclonal antibody was created to bond to, as opposed to the drug itself not being potentially a good thought as far as help for lupus nephritis. That’s one trial that is in process, and it’s called ALLEGORY trial. The CD40 antibody dapirolizumab. That one is a polyethylene glycol, a pegylated antibody fragment of the CD40 ligand, that targets CD40 ligand. And it does not have a functional Fc domain, so basically some previous trials looking at similar molecules had some problems with thromboembolic adverse effects. By making this difference, with it not have that functional Fc domain, the thought is that there will not be as much of a problem with thromboembolic adverse effects. That is another drug that is being looked at in regard to SLE as well. And I believe that one is a phase 2 trial. Then there is also BIIB059, which is another drug that doesn’t have a name yet. That is the TOPAZ trial, and it’s in phase 3 at this time. And it’s a humanized monoclonal antibody, and it binds blood dendritic cell antigen 2, and that’s a dendritic cell specific receptor. And it inhibits the production when it binds to interferon as well, so the thought is that the interferon decreased cytokine up regulation and hopefully decrease lupus activity. Anifrolumab, we’ve already talked about. That’s FDA-approved already, I won’t spend too much time there because I’m sure people are familiar with that. However, as far as lupus SLE, but there is also a phase 3 trial called the IRIS trial looking at anifrolumab for lupus nephritis class 3 or class 4, and it can be either with or without class 5. That is also another study ongoing looking at specifically lupus nephritis for an additional indication for anifrolumab. And then also there is voclosporin, which has already hit the market. It’s FDA-approved, which is a small molecule calcineurin inhibitor. And that can be used for lupus nephritis. And then finally there are some trials, phase 3 trials looking at secukinumab for SLE as well. And that’s a human IgG1 monoclonal antibody, and it selectively bonds to IL-17A. And so quite a few things in the pipeline. Unfortunately, lupus trials have a reputation for not necessarily meeting outcomes. For example, TULIP-1 and TULIP-2 for anifrolumab. Because it’s such a heterogeneous disease, that makes it so difficult sometimes to truly meet the outcomes in a super specific way, where you have p-values that are very small. And I’m open to seeing what’s going to happen with these trials, so hopefully out of this pack of drugs that we’ve talked about that are in trials, we’ll see a couple that will become FDA-approved that we can add to our armamentarium.

Transcript Edited for Clarity