Merck KGaA has shed more light on the failure of its lupus drug in one cohort of patients, while pointing to secondary endpoint readouts as proof that the candidate still deserves a shot at seeking approval.
The German pharma evaluated the oral TLR7/8 inhibitor, called enpatoran, in the phase 2 WILLOW study that separately assessed the drug in cohorts. Cohort A, which included patients with either cutaneous lupus erythematosus or systemic lupus erythematosus (SLE), hit its primary endpoint of demonstrating a clinically meaningful improvement in week 16 as measured by the CLE Disease Area and Severity Index.
But Merck revealed back in March that cohort B, which enrolled patients with SLE, had missed its primary endpoint, which assessed responses on a composite scale after 24 weeks of daily dosing.
In a presentation at the 2025 European Congress of Rheumatology in Barcelona, Merck said that all doses of enpatoran in cohort B were associated with higher response rates compared with placebo as measured by British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rate. However, the company didn’t share this specific data and reaffirmed that the cohort had missed this key endpoint.
Instead, the drugmaker pointed out that among a subgroup of patients with active skin disease, BICLA response rates were up to 58.6% for patients receiving enpatoran while placebo response rates were 31.7%. Over 58% of these patients who received enpatoran showed a 70% or greater improvement in skin disease activity compared to 26.8% of those on placebo, Merck noted.
When it came to the primary endpoint as measured by BICLA, “higher and relevant” response rates were seen among a subgroup of patients with high corticosteroid use, according to Merck, who again didn’t provide any specific data.
“The efficacy and tolerability results from cohort B, including among those with active skin involvement—a manifestation that affects most lupus patients—are consistent with our observations from cohort A,” said Jan Klatt, Head of Development Unit Neurology and Immunology for the Healthcare business of Merck.
“We are set to initiate regulatory discussions with key health authorities to determine the most effective pathway for bringing enpatoran to patients,” Klatt added in the release.
Enpatoran, which Merck is also studying in idiopathic inflammatory myopathies, is one of the two most advanced assets in the company’s neurology and immunology pipeline. Cladribine, the other advanced candidate, is in phase 3 development as a treatment for generalized myasthenia gravis.