Glenn Newberry in an earlier post today was asking whether Benlysta from GlaxoSmithKline (GSK), being trialled for lupus nephritis, poses any threat to Aurinia (AUPH).
Benlysta is a monoclonal antibody that binds to and inhibits BAFF (B-cell activating factor). A company called Anthera (ANTH) is trialling blisibimod, an oral agent that does the same thing. Benlysta is hardly new… it’s lurked without a niche for years, after a disappointing trial in lupus where more patients died in the treatment arm than in the control arm. I formerly tracked Anthera but admit I’m not current with it. I would admit that as regards voclosporin, a calcineurin inhibitor, it’s not totally unreasonable theoretically to argue that a BAFF inhibitor and a calcineurin inhibitor might bring about similar, or somewhat similar, therapeutic effects. The theory of course means nothing unless borne in good ol’ you know what: randomized controlled clinical trials. And my sense from those is that BAFF inhibition has globally disappointed.
Despite what I said above about Benlysta, it IS FDA approved for lupus and generates about $380M in annual sales. Benlysta has some bone marrow suppressive actions and also deters plasma cell maturation. By contrast, blisibimod mostly failed in systemic lupus, but is still in prospective development for IgA nephropathy.
OK, here the going gets murky, but let me try to bring some insight to this discussion. Will Benlysta succeed in phase 3 for LN? I think it’s a two-fold answer… that it may “succeed” and that it also won’t matter for Aurinia.
Here’s why. First, as I see it, how GSK arrived at this trial is murky. To the best of my knowledge, only limited proof of concept trials have been done with Benlysta in LN and I’m having a hard time tracking them down. I SEEM to recall, but cannot find documentation of it, that Mary Anne Dooley, MD, lead investigator for Aurinia’s phase 3 study, was once involved in a trial of Benlysta for LN and didn’t like the performance much. But I can’t recall where I read that. A vitally important issue in this is how you gauge and quantify “success” in LN (and I will explain why I think GSK has done a cynical punt). Check out, for example, this reference.
There have been a plethora of scoring and grading schemes for LN over the years, because there has been little consensus on how ...