Janssen Halts Phase 3 LOTUS Trial of Stelara in Systemic Lupus Erythematosus Due to Lack of Efficacy

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Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, recently announced thatDecision to Terminate the Phase III LOTUS Study (NCT03517722) Evaluating the Anti-Inflammatory Drug Stelara (ustekinumab) for the Treatment of Systemic Lupus Erythematosus (SLE) Due to Insufficient Efficacy。

LOTUS is a global, randomized, double-blind, placebo-controlled, parallel-group Phase III study conducted in patients with active systemic lupus erythematosus (SLE). The study enrolled a total of 516 patients, including representatives from underrepresented populations severely affected by lupus. The primary endpoint was the proportion of patients achieving an SRI-4 (SLE Responder Index 4) response at Week 52 of treatment. SRI-4 is a composite assessment tool that combines scores from three different, validated lupus disease activity indices to define responders and non-responders.

Data from a pre-planned interim efficacy analysis showed that Stelara did not demonstrate significant efficacy compared with placebo. Interim safety results were consistent with the known safety profile of Stelara, and no new safety signals were identified.

Based on the results of this interim analysis, Johnson & Johnson has decided to terminate the LOTUS study. Notably, as a result of this decision, the second Phase III study, LOTUS-C (NCT04060888), originally scheduled to commence in China in June this year, will not be initiated. This study was originally planned to enroll 190 patients with active systemic lupus erythematosus (SLE).

The launch of the LOTUS program is based on data from the STELARA SLE study, a global placebo-controlled Phase II trial successfully completed in 2017. During the 24-week double-blind period, a significantly higher proportion of patients in the Stelara treatment group achieved an SRI-4 response compared with the placebo group (62% vs. 33%, p=0.0057), thereby meeting the primary endpoint of the study. Furthermore, among patients who switched from placebo to Stelara at Week 24 and continued treatment for up to one year, 63% achieved an SRI-4 response.

It should be noted that the decision to terminate the LOTUS program will not affect other ongoing studies of Stelara or its currently approved indications.

Stelara is a monoclonal antibody that targets interleukin-12 (IL-12) and interleukin-23 (IL-23). By binding to the p40 subunit shared by IL-12 and IL-23, it prevents their interaction with cell surface receptors, thereby inhibiting these two pro-inflammatory cytokines. IL-12 and IL-23 are naturally occurring proteins believed to play a key role in immune-mediated inflammatory diseases.

Stelara was launched in 2009 and has been approved for multiple therapeutic indications, including: (1) adolescent (≥12 years of age) and adult (≥18 years of age) patients with moderate to severe plaque psoriasis; (2) adult patients with active psoriatic arthritis (PsA); (3) adult patients with moderately to severely active Crohn’s disease (CD); and (4) adult patients with moderately to severely active ulcerative colitis (UC).

In China, Stelara was approved for launch in November 2017 for the treatment of moderate-to-severe plaque psoriasis. In March this year, the drug received approval for its second indication, for use in adult patients with moderate-to-severe Crohn’s disease (CD).

In 2019, Stelara achieved sales of $6.361 billion. In January this year, the pharmaceutical market research firm Evaluate Vantage published an article in Nature Reviews Drug Discovery, predicting that Stelara’s global sales this year would reach $7.241 billion, ranking seventh among the “Top 10 Best-Selling Drugs Worldwide in 2020.”

Reference Source: Janssen Announces Discontinuation of Phase 3 LOTUS Study Evaluating Ustekinumab in Systemic Lupus Erythematosus