GLPG3667 Meets Primary Endpoint in Dermatomyositis, Misses in SLE Phase 3 Trials

GLPG3667 met its primary endpoint of Total Improvement Score (TIS) at week 24 in a phase 3-enabling dermatomyositis (DM) study but failed to achieve statistical significance in a parallel systemic lupus erythematosus (SLE) trial, according to topline results released by Galapagos.1

In a December 18, 2025, press release, Galapagos reported numerical improvements across several secondary endpoints in the phase 3 GALACELA SLE study that did not reach statistical significance, while the investigational therapy met its primary endpoint in the phase 3-enabling GALARISSO DM trial.1

“The results from the GALARISSO study demonstrate that GLPG3667 has the potential to become an important new treatment option for patients living with dermatomyositis, a debilitating autoimmune disease with limited therapeutic alternatives,” Rohit Aggarwal, MD, MS, medical director of rheumatology of the University of Pittsburgh Medical Center, said in a statement. “Furthermore, the improvements in patients’ disease activity observed in the study are encouraging. We look forward to further analyzing the data, including the long-term follow-up study with GLPG3667 in this indication.”1

GLPG3667 is an investigational, reversible, and selective tyrosine kinase 2 (TYK2) kinase domain inhibitor. Previously, in a phase 2 trial evaluating efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics in adults with active SLE, GLPG3667 met its primary endpoint of the proportion of patients achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at week 32.1,2

The phase 3 GALACELA SLE study remains ongoing, with final week 48 data expected in the second quarter of 2026, and is set to further inform the overall assessment of efficacy, safety, and determine potential next steps for the SLE development program.1

In the randomized, double-blind, placebo-controlled, multicenter, phase 3-enabling proof-of-concept GALARISSO study, investigators evaluated the efficacy and safety of GLPG3667 in adults with DM. Participants received once-daily oral GLPG3667 150 mg (n = 21) or placebo (n = 19), with a 24-week primary endpoint.1

The primary endpoint of TIS was based on American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria, with a pre-specified threshold of statistical significance set at 10% (alpha [α], 0.1). Secondary endpoints included the proportion of patients achieving minimal improvement per ACR/EULAR criteria, change in Modified Cutaneous Dermatomyositis Disease Area and Severity Index Activity Score (m-CDASI-A), change in Health Assessment Questionnaire–Disability Index (HAQ-DI), and change in Manual Muscle Test (MMT-8).1

Investigators reported that GLPG3667 met the primary endpoint of TIS at week 24 compared with placebo (P = .0848), with a between-group difference of 14.26 points. According to the company, GLPG3667 also showed improvements on several secondary endpoints of disease activity, including TIS20, TIS40, TIS60, and m-CDASI-A2, and demonstrated a favorable safety and tolerability profile throughout the 24-week treatment period.1,2

“The positive results from the GALARISSO study in patients with dermatomyositis further validate the anti-inflammatory potential of our selective TYK2 inhibitor, consistent with findings from our earlier Phase 1b psoriasis study and supportive in vitro pharmacology,” said Henry Gosebruch, CEO of Galapagos, in the statement. “We are encouraged by the favorable safety profile observed to date, which may contribute to the differentiated profile of GLPG3667.”1

Galapagos has stated it will continue to evaluate strategic alternatives, including resumption of its partnering process, to accelerate further development of GLPG3667 in DM and potentially other severe autoimmune indications.1

References

1. Galapagos announces start of Phase 2 study with selective TYK2 inhibitor, GLPG3667, in patients with active systemic lupus erythematosus. Galapagos. Published January 4, 2024. Accessed December 19, 2025. https://www.glpg.com/press-releases/galapagos-announces-start-of-phase-2-study-with-selective-tyk2-inhibitor-glpg3667-in-patients-with-active-systemic-lupus-erythematosus/

2. Galapagos NV. Galapagos Announces Topline Results from Two Phase 3-Enabling Studies with Selective TYK2 Inhibitor GLPG3667 in Dermatomyositis and Systemic Lupus Erythematosus. GlobeNewswire News Room. Published December 18, 2025. Accessed December 19, 2025. https://www.globenewswire.com/news-release/2025/12/18/3208166/0/en/Galapagos-Announces-Topline-Results-from-Two-Phase-3-Enabling-Studies-with-Selective-TYK2-Inhibitor-GLPG3667-in-Dermatomyositis-and-Systemic-Lupus-Erythematosus.html

3. ‌Business Insider. Galapagos Announces Topline Results from Two Phase 3-Enabling Studies with Selective TYK2 Inhibitor GLPG3667 in Dermatomyositis and Systemic Lupus Erythematosus. markets.businessinsider.com. Published December 18, 2025. Accessed December 19, 2025. https://markets.businessinsider.com/news/stocks/galapagos-announces-topline-results-from-two-phase-3-enabling-studies-with-selective-tyk2-inhibitor-glpg3667-in-dermatomyositis-and-systemic-lupus-erythematosus-1035658664