Blisibimod SLE trial fails to reach primary endpoint
medwireNews: The phase III CHABLIS-SC1 trial comparing blisibimod with placebo in patients with systemic lupus erythematosus (SLE) has not reached its primary endpoint of improvement in the SLE responder index (SRI) at 1 year, researchers report.
The selective inhibitor of B-cell activating factor (BAFF) did not show significant benefits in the trial population enriched for disease characteristics that have been shown to be associated with greater treatment effects, say the CHABLIS-SC1 (Clinical and Health Assessments with Blisibimod SC, Study 1) investigators.
Nonetheless, “blisibimod was associated with successful steroid reduction, decreased proteinuria and biomarker responses,” leading Renee Martin (Anthera Pharmaceuticals, Inc, Hayward, California, USA) and colleagues to suggest it might have “important clinical benefits.”
An earlier, phase II trial involving blisibimod also failed to meet its primary efficacy endpoint but upheld observations in phase III trials of targeted BAFF inhibitors showing greater treatment effect among certain patients, namely those with higher disease activity, greater corticosteroid doses, antibodies against double stranded (ds)DNA, and low complement C3 or 4.
The double-blind CHABLIS-SC1 trial examined this further in 442 SLE patients with antinuclear antibodies or anti-dsDNA and a score of at least 10 on the Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA–SLEDAI) despite receiving standard-of-care medications. Participants were randomly assigned to receive weekly 200 mg subcutaneous blisibimod or placebo with steroid taper encouraged from week 8.
The primary endpoint was the proportion of patients who had a response as per the composite SRI-6 index at week 52, which was defined as: a 6 point or greater reduction in SELENA–SLEDAI score compared with baseline; no new British Isles Lupus Assessment Group (BILAG) A organ domain scores or no more than one new BILAG B organ domain score at time of assessment compared with baseline; and no worsening in the Physician’s Global Assessment score.
This endpoint was achieved by a comparable 46.9% of the blisibimod group and 42.3% of the control group, the researchers report in the Annals of the Rheumatic Diseases.
Nonetheless, blisibimod-treated participants were significantly more likely to achieve corticosteroid taper over weeks 40–52 compared with placebo, with rates of 17.2% and 8.9%, respectively.
And treatment with blisibimod was associated with a significant increase in complement C3 and C4 as well as decreases in anti-dsDNA levels, which did not reach statistical significance.
Finally, decreases in the urinary protein:creatinine ratio (UPCR) were greater with blisibimod than placebo regardless of the baseline UPCR levels. And in the subgroup of patients with a baseline UPCR of at least 56.5 mg/mmol or more, significantly more blisibimod-treated individuals achieved a greater than 50% reduction in UPCR, a reduction in UPCR to below 56.5 mg/mmol, or a UPCR equal to or less than three times the upper limit of normal.
By Anita Chakraverty
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group