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.
Merck had evaluated the oral TLR7/8 inhibitor, called enpatoran, in the phase 2 WILLOW study that separately assessed the drug in two forms of lupus. Peter Guenter, CEO of healthcare at Merck, disclosed back in October 2024 that the primary endpoint had been reached for a cohort of the trial involving patients with either cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) that included organ-specific disease activity.
At the time, Guenter claimed this portion of the study had found “very strong and unambiguous proof of concept in cutaneous lupus.” However, the company didn’t offer up detailed data as proof.
Concerns about the viability of enpatoran mounted in March of this year, when Merck disclosed that the drug had failed to hit the key endpoint of the other cohort of the trial, which was focused on patients with SLE only. The German company insisted at the time that it had seen “promising responses” in predefined subgroups of patients of the trial, which supported further development.
Now, Merck has offered up data from the successful first cohort to justify its intention to push the enpatoran program into phase 3.
Specifically, enpatoran demonstrated a clinically meaningful improvement at week 16 as measured by the CLE Disease Area and Severity Index.
By week 24, 91.3% of patients had seen a 50% of greater improvement in this score from baseline, while 60.9% had seen a 70% or greater improvement. These changes compared with a 38.5% and 11.5% rate, respectively, in the placebo cohort.
These patients also showed that enpatoran was well-tolerated and “exhibited a manageable safety profile consistent with previous studies, with no new safety signals identified,” Merck said.
“We are encouraged by the WILLOW results, where we observed clinically meaningful efficacy with a favorable safety profile in people living with lupus rash,” said Jan Klatt, Head of Development Unit Neurology & Immunology for Merck Healthcare. “Based on these results, discussions with health authorities on a global phase 3 program with enpatoran are underway.”
The pharma was able to use data from the CLE cohort to back up its premise that selectively blocking the activation of toll-like receptors 7 and 8, which are associated with severe lupus cases, can increase the effectiveness of treatment. In fact, enpatoran led to a rapid reduction in interferon gene signature scores beginning at week 2 and maintained to week 24, Merck said.
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.