Boehringer Ingelheim officially unveiled fibrosis data from a mid-stage trial of its Zealand Pharma-partnered drug in MASH on Friday, after its liver congress abstract was “unintentionally and temporarily” published Thursday.
Liver scarring results from the survodutide trial in metabolic dysfunction-associated steatohepatitis were eagerly anticipated as the companies only previously reported MASH improvement data without worsening of fibrosis. The MASH, or NASH, race is heating up with blockbuster GLP-1 drugs eyeing market territory beyond weight loss and diabetes, with non-GLP-1 candidates also in hot pursuit.
According to a subgroup analysis from the Phase 2 survodutide study, up to 64.5% of treatment arm patients with moderate (F2) and advanced (F3) liver scarring saw a minimum one-stage improvement in fibrosis without worsening of disease at 48 weeks, versus 25.9% with placebo (p=0.0005).
Waheed JamalThe placebo-corrected liver scarring response was therefore around 39%, Waheed Jamal, Boehringer’s global head of cardiovascular and metabolic medicine, told Endpoints News in an interview. “This is more than we’ve seen for any other [GLP-1] compounds to date,” he said.
On Wednesday, Eli Lilly also unveiled liver scarring data from its Phase 2 tirzepatide trial in MASH. In that study, 51% to 54.9% of patients with F2 and F3 fibrosis across three tirzepatide treatment arms achieved a minimum one-stage improvement in liver scarring without disease worsening at 52 weeks, versus 21.3% to 25.2% of placebo cohorts.
GLP-1 is absent in the liver but glucagon and GIP are present. According to Jamal, the key difference between the two candidates is that survodutide acts on GLP-1 and glucagon, and that glucagon is highly expressed in the liver. This is in contrast to GLP-1s and other incretins that work indirectly as they aim to reduce weight to reduce liver fat, he said. Tirzepatide is a GIP/GLP-1 receptor dual agonist.
In MASH, high liver fat paves the way to inflammation and ballooning, which can then lead to fibrosis and cirrhosis.
Boehringer’s Phase 2 trial tested 2.4 mg, 4.8 mg and 6 mg survodutide in 295 adults with MASH who also have F1 (mild) to F3 fibrosis with and without type 2 diabetes. In the broader trial population, up to 52.3% of treated patients saw a “significant improvement” in liver scarring at 48 weeks, versus 25.8% of placebo patients (p<0.01).
Madrigal Pharmaceuticals’ registrational test for its FDA-approved THR-β agonist Rezdiffra saw 26% of patients achieve a minimum one-stage improvement in liver fibrosis at 24 weeks. Akero’s FGF21 analog efruxifermin has produced the highest fibrosis improvement to date with 75% at 96 weeks in its Phase 2b trial.
Boehringher’s Friday data add to a positive Phase 2 primary endpoint readout in February, which showed that up to 83% of survodutide patients had a “statistically significant improvement” in their disease versus 18.2% with placebo. Jefferies projects that survodutide could pull $10 billion in peak sales.