Merck KGaA's Lupus Drug Shows Mixed Results in Phase 2 Trial

Merck KGaA has released additional data from its phase 2 WILLOW study evaluating enpatoran, an oral TLR7/8 inhibitor, in patients with lupus. The results paint a complex picture of the drug's potential, with promising outcomes in some patient subgroups despite missing a key endpoint.

Cohort B Misses Primary Endpoint, but Shows Promise in Subgroups

The German pharmaceutical company revealed that cohort B of the WILLOW study, which enrolled patients with systemic lupus erythematosus (SLE), failed to meet its primary endpoint. This endpoint assessed responses on a composite scale after 24 weeks of daily dosing.

However, Merck highlighted several positive findings from the study:

• All doses of enpatoran in cohort B were associated with higher response rates compared to placebo, as measured by the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rate.
• In a subgroup of patients with active skin disease, BICLA response rates reached up to 58.6% for patients receiving enpatoran, compared to 31.7% for those on placebo.
• Over 58% of patients with active skin disease who received enpatoran showed a 70% or greater improvement in skin disease activity, versus 26.8% of those on placebo.
• A subgroup of patients with high corticosteroid use demonstrated "higher and relevant" response rates on the primary endpoint, although specific data were not provided.

Cohort A Success and Future Plans

Merck KGaA previously reported that cohort A of the WILLOW study, which included patients with either cutaneous lupus erythematosus or SLE, met its primary endpoint. This cohort demonstrated a clinically meaningful improvement at week 16 as measured by the CLE Disease Area and Severity Index.

Jan Klatt, Head of Development Unit Neurology and Immunology for Merck's Healthcare business, stated, "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."

Despite the mixed results, Merck remains optimistic about enpatoran's potential. Klatt added, "We are set to initiate regulatory discussions with key health authorities to determine the most effective pathway for bringing enpatoran to patients."

Enpatoran's Role in Merck's Pipeline

Enpatoran is one of two advanced assets in Merck KGaA's neurology and immunology pipeline. The company is also studying the drug for idiopathic inflammatory myopathies. The other advanced candidate, cladribine, is currently in phase 3 development as a treatment for generalized myasthenia gravis.

As Merck KGaA moves forward with its plans for enpatoran, the pharmaceutical industry will be watching closely to see how regulatory authorities respond to the mixed phase 2 results and whether the drug will advance to phase 3 trials in lupus.