Merck KGaA Continues Enpatoran Development Despite Phase 2 SLE Trial Setback

Merck KGaA has faced a challenge in the clinical evaluation of its investigational oral TLR7/8 inhibitor, enpatoran, for systemic lupus erythematosus (SLE). Although the drug did not achieve the primary endpoint in the latest phase 2 trial, the company has determined that continued development is justified. This decision is based on the positive responses observed in certain patient subgroups, as well as the encouraging results previously reported in a different form of lupus.
The phase 2 study was designed to assess enpatoran in two distinct patient populations: individuals diagnosed with systemic lupus erythematosus and those affected by cutaneous lupus erythematosus (CLE). In late 2023, Merck disclosed that the CLE cohort had exhibited favorable outcomes, indicating a meaningful therapeutic effect in that group.

However, the portion of the study focused on SLE patients did not meet its primary objective, which involved evaluating treatment responses through a composite scale after 24 weeks of daily administration. Despite this overall outcome, Merck noted that certain predefined subgroups demonstrated promising responses to the treatment. Given these subgroup findings, combined with the CLE success and enpatoran’s safety profile, the company has decided to move forward with further research and clinical evaluation.
At this stage, Merck has not provided specific data to substantiate its conclusions. Instead, the company has relied on qualitative assessments of the study results to justify its decision. The safety profile of enpatoran also played a key role in the company’s decision-making process, as it suggests a favorable risk-benefit balance that may support continued investigation.
Enpatoran remains one of the most advanced assets within Merck’s neurology and immunology research pipeline. In addition to its potential applications in lupus, the company is also studying the drug’s efficacy in treating idiopathic inflammatory myopathies. Alongside enpatoran, cladribine represents another key candidate within Merck’s portfolio, currently progressing through phase 3 development as a potential treatment for generalized myasthenia gravis. The strategic importance of these two drug candidates has grown, particularly in light of setbacks experienced with other investigational compounds.

Merck’s shifting clinical priorities reflect broader challenges in drug development. In 2020, the company identified enpatoran, evobrutinib, and xevinapant as three key programs expected to drive future growth. However, evobrutinib was discontinued after failing to meet expectations in a phase 3 trial in late 2023, while xevinapant was dropped in mid-2024 following an interim phase 3 analysis that indicated it was unlikely to deliver the desired outcomes. These developments have reinforced the importance of enpatoran and cladribine in Merck’s ongoing research and development efforts.