One of Merck KGaA’s leading immunology assets has flunked a phase 2 lupus trial. Despite the primary endpoint miss, Merck has concluded (PDF) further development is warranted in light of responses seen in subgroups and a recent win in another form of the disease.
Merck tested its oral TLR7/8 inhibitor enpatoran in two forms of lupus. The company reported positive phase 2 data from the cohort of cutaneous lupus erythematosus (CLE) patients late last year. Thursday, Merck revealed the systemic lupus erythematosus (SLE) cohort was less successful. The SLE arm missed its primary endpoint, which assessed responses on a composite scale after 24 weeks of daily dosing.
The German drugmaker said it saw “promising responses” in predefined subgroups of patients. Considering the subgroup responses, CLE results and safety profile, Merck judged that the totality of data supports further development.
Merck is yet to share the data underpinning its conclusion, with updates to date limited to qualitative assessments of the results. Peter Guenter, CEO of healthcare at Merck, disclosed the CLE success at the company’s Capital Markets Day in October, telling analysts the trial found “very strong and unambiguous proof of concept in cutaneous lupus.”
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.
The importance of enpatoran and cladribine to Merck has increased as other prospects have flamed out. Four years ago, Merck named (PDF) enpatoran, evobrutinib and xevinapant as three important clinical programs that it expected to help fuel its “next wave of growth.” Evobrutinib failed a phase 3 trial in late 2023 and was quickly axed, while Merck dropped xevinapant in June 2024 after an interim phase 3 analysis.