Lupus hopes dashed for ustekinumab after Phase 3 trial discontinued

The high expectations for the anti-IL 12/23 antibody ustekinumab (Stelara) in SLE based on Phase 2 trial results have not been borne out in larger Phase 3 studies.

Manufacturer Janssen has announced it is discontinuing the Phase 3 LOTUS study of ustekinumab in SLE due to lack of efficacy seen in preliminary results.

LOTUS was a multination study that enrolled 516 patients with active SLE in a randomised, double-blind, placebo-controlled, parallel-group phase 3 study. The primary endpoint was the proportion of participants with a composite measure of SRI-4 (Systemic Lupus Responder Index) response at Week 52.

The trial investigated a regimen of ustekinumab 6mg IV then 90mg SC at week 8 and at 8 week intervals thereafter, compared to placebo in addition to standard of care treatment for SLE. It was originally intended to run up to 2021, with a further two year extension period to 2023.

The company says the decision to discontinue the trial was based on data from a pre-planned interim efficacy analysis. However no new safety signals were identified in the interim safety analysis. Janssen said it intended to thoroughly analyse the totality of the study data and publish findings.

“Lupus patients are waiting for better treatments, which makes this outcome disappointing,” said Dr Alyssa Johnsen, Janssen’s Rheumatology Disease Area Leader.

“Our hope is that by ultimately sharing these data with the scientific community we can help inform lupus research and therefore still have a positive impact on the lives of patients living with SLE. Janssen continues to be strongly committed to research and development of novel therapies for lupus.”

Ustekinumab had shown promising results in a randomised controlled trial in 102 patients with active SLE, proving to be significantly better than placebo in improving clinical parameters of the disease.

The international multicentre trial, which included patients from Australia, found that at 24 weeks, 37 of 60 patients (62%) in the ustekinumab group achieved an SRI-4 response compared to 33% in the placebo group.

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