Merck KGaA Advances Lupus Drug to Phase 3 Despite Mixed Results
Enpatoran Shows Promise in Cutaneous Lupus, Fails in Systemic Lupus
Merck KGaA, the German pharmaceutical giant, has unveiled data supporting its decision to advance enpatoran, an oral TLR7/8 inhibitor, into phase 3 trials for lupus treatment. This move comes despite mixed results from the phase 2 WILLOW study, which evaluated the drug in two forms of the autoimmune disease.
Positive Outcomes in Cutaneous Lupus
The WILLOW study's first cohort, focusing on patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) with organ-specific disease activity, demonstrated significant efficacy. By week 24, 91.3% of patients treated with enpatoran showed a 50% or greater improvement in the CLE Disease Area and Severity Index, compared to 38.5% in the placebo group. Moreover, 60.9% of treated patients achieved a 70% or greater improvement, versus 11.5% in the placebo cohort.
Jan Klatt, Head of Development Unit Neurology & Immunology for Merck Healthcare, expressed enthusiasm about the results: "We are encouraged by the WILLOW results, where we observed clinically meaningful efficacy with a favorable safety profile in people living with lupus rash."
Setback in Systemic Lupus Arm
Despite the positive outcomes in CLE, enpatoran failed to meet the primary endpoint in the study's other cohort, which focused solely on SLE patients. This setback, disclosed in March 2025, raised concerns about the drug's viability. However, Merck maintains that "promising responses" were observed in predefined subgroups, justifying further development.
Mechanism of Action and Safety Profile
Enpatoran's mechanism of action involves selectively blocking the activation of toll-like receptors 7 and 8, which are associated with severe lupus cases. The drug demonstrated a rapid reduction in interferon gene signature scores, beginning at week 2 and maintained through week 24.
Safety data from the WILLOW study indicate that enpatoran was well-tolerated, exhibiting a "manageable safety profile consistent with previous studies, with no new safety signals identified," according to Merck.
Future Prospects and Pipeline Update
Based on the encouraging results from the CLE cohort, Merck is now in discussions with health authorities regarding a global phase 3 program for enpatoran. The company is also studying the drug's potential in idiopathic inflammatory myopathies.
Enpatoran represents one of two advanced assets in Merck's neurology and immunology pipeline, alongside cladribine, which is in phase 3 development for generalized myasthenia gravis.
As Merck KGaA continues to navigate the complex landscape of lupus treatment, the pharmaceutical industry watches closely to see if enpatoran can overcome its mixed results and emerge as a viable therapy for this challenging autoimmune condition.
References
- Merck KGaA shares data justifying pushing lupus drug into phase 3—despite recent setback
Despite Merck KGaA’s lupus drug failing to prove itself against one form of the autoimmune disease, the German drugmaker has now shared the data to back up its belief that the therapy still has promise.
Explore Further
What are the specific findings and metrics from the phase 2 WILLOW study's primary endpoint for systemic lupus arm?
What other treatments currently exist for cutaneous lupus erythematosus (CLE) and how does enpatoran compare?
What are the strategic reasons behind Merck KGaA’s decision to continue with phase 3 trials despite mixed phase 2 results?
What potential does enpatoran have in the treatment of idiopathic inflammatory myopathies according to ongoing studies?
How might enpatoran's safety profile impact its commercial viability compared to existing lupus therapies?