by DrKSSMDPhD | September 8, 2017 4:01 pm
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 to assess and measure the disease and the response to treatment. In this regard, one MUST praise Aurinia for rolling up its sleeves, taking “command” of the literature and really clarifying a cogent response to assessing LN and how it behaves when treated, and coming up with plausible definitions for what “success” in therapy is. GSK, by contrast, seems to wield little expertise in the disease. The kicker is this: pull up the phase 3 protocol GSK is operating under .
The primary endpoint of the study is ANY renal response to Benlysta, after which there is tweakology in secondary endpoints. This is not a “real” phase 3 study following a good phase 2, methinks. It is a functional phase 2 study with proof of concept attributes being called phase 3 because it is huge, multicentered and with randomized double masking attributes. It is a plus-size phase 2 study… an excursion. Naturally, however, the results will be positive because of how the primary outcome is set. Will the positivity matter? I don’t think it will… I don’t think the efficacy seen will in any way rival or threaten voclosporin.
And it gets worse from there: this is a parenteral med (Benlysta is an injection) whilst voclo is oral. Which would YOU prefer? We don’t know where voclo will be priced, but it will NOT be $30K a year the way Benlysta is… a price point so high that NICE has banned it in the UK because “return on investment,” how much health one derives per dollar spent on it, is considered unacceptable by European medical thrift standards.
An editorial comment: I know a lot about calcineurin inhibitors, and perceive them as suitably much more “diffuse” in their actions than an agent like Benlysta. In a complex disease like LN, this is highly desirable. We’ve said from the beginning: voclosporin is eerily a Goldilocks fit for LN, and I doubt Benlysta will be.
Long winded answer. Long AUPH. In my view, the GSK trial will serve as a foil and drive some AUPH shorting but will not affect the endgame success of AUPH and voclosporin. It’s merely a sideshow.
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