Orelabrutinib Achieves Primary Endpoint in Phase 2b SLE Trial

The phase 2b study of InnoCare Pharma’s orelabrutinib met its primary endpoint of SLE Response Index-4 (SRI-4) response at week 48 in patients with systemic lupus erythematosus (SLE).1

The therapy has also received approval from the Center for Drug Evaluation to conduct a phase 3 registrational clinical trial, further supporting the clinical potential of the Bruton’s tyrosine kinase (BTK) inhibitor.1

“SLE patients have huge unmet clinical needs, requiring long-term or even lifelong medication that severely impacts their quality of life,” said Jasmine Cui, co-founder, chairperson, and CEO of Innocare Pharma, in a statement. “We are happy to see that the phase IIb study of orelabrutinib for SLE has met its primary endpoint with outstanding efficacy and has received approval to conduct a phase 3 registrational trial. We will continuously accelerate clinical development to provide better treatment options for patients with SLE and other autoimmune diseases.”2

A small-molecule BTK inhibitor, orelabrutinib, is a late-stage, central nervous system–penetrant therapy designed to cross the blood–brain barrier. The agent is also advancing into phase 3 evaluation for primary and secondary progressive multiple sclerosis, underscoring its broader therapeutic potential.¹

Investigators conducted a multicenter, randomized, double-blind, placebo-controlled trial in which participants were assigned 1:1:1 to receive orelabrutinib 75 mg once daily, orelabrutinib 50 mg once daily, or placebo. The study’s primary endpoint was the SRI-4 response rate at week 48, with secondary endpoints including SRI-6 and BILAG-based Composite Lupus Assessment (BICLA).1,4

An SRI-4 response is defined as a reduction in the SLE Disease Activity Index (SLEDAI) score of ≥4 points, with no worsening of the BILAG index and no deterioration from baseline of ≥0.3 points in the physician global assessment.³

The phase 2b study enrolled 187 adult patients with SLE receiving standard-of-care therapy. Prespecified subgroup analyses included patients with baseline BILAG ≥1A or ≥2B, as well as those with BILAG ≥1A or ≥2B and a clinical SLEDAI-2K score ≥4.1,2

At week 48, investigators reported a statistically significant improvement in SRI-4 response rate among patients receiving orelabrutinib 75 mg once daily compared with placebo (57.1% vs 34.4%; P <.05). A dose-dependent trend was observed, with increased response rates in the 75 mg group compared with the 50 mg group.1

Patients treated with orelabrutinib 75 mg once daily also demonstrated significantly increased SRI-6 and BICLA response rates compared with placebo (P <.05), meeting all secondary endpoints. The safety profile was generally well tolerated and consistent with the known mechanism of BTK inhibition and the underlying disease biology of SLE.1,2

In patients with baseline BILAG ≥1A or ≥2B, the placebo-adjusted difference in SRI-4 response rate with orelabrutinib 75 mg once daily was 35%. Among patients with baseline BILAG ≥1A or ≥2B and a clinical SLEDAI-2K score ≥4, the placebo-adjusted difference in SRI-4 response rate was 43%.2

References

1. Zenas BioPharma (USA) LLC. Zenas BioPharma’s Partner, InnoCare Pharma, Announces Achievement of Primary Endpoint in Phase 2b Study of Orelabrutinib, a BTK Inhibitor, for Systemic Lupus Erythematosus. GlobeNewswire News Room. Published December 15, 2025. Accessed December 15, 2025. https://www.globenewswire.com/news-release/2025/12/15/3205293/0/en/Zenas-BioPharma-s-Partner-InnoCare-Pharma-Announces-Achievement-of-Primary-Endpoint-in-Phase-2b-Study-of-Orelabrutinib-a-BTK-Inhibitor-for-Systemic-Lupus-Erythematosus.html

2. Innocarepharma.com. Published 2025. Accessed December 15, 2025. https://www.innocarepharma.com/m/en/news/activity/en0202512141-Primary-Endpoint-of-Phase-IIb-of-Orelabrutinib-for-SLE-Achieved-and-Phase-III-Clinical-Trial-Approved

3. Connelly K, Kandane‐Rathnayake R, Hoi A, et al. Association of Modified Systemic Lupus Erythematosus Responder Index Attainment With Long‐Term Clinical Outcomes: A Five‐Year Prospective Study. Arthritis & Rheumatology. 2022;75(3):401-410. doi:https://doi.org/10.1002/art.42350

4. Clinicaltrials.gov. Published 2025. Accessed December 15, 2025. https://clinicaltrials.gov/study/NCT05688696