Boehringer launches two Phase III trials after MASH therapy breakthrough

Boehringer Ingelheim has been granted a breakthrough therapy designation by the US Food and Drug Administration (FDA) for its drug survodutide, intended to treat non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate or advanced fibrosis. This designation aims to accelerate the evaluation and review of the drug, based on early clinical evidence of its efficacy.

In tandem with this development, Boehringer has initiated two Phase III clinical trials, named LIVERAGE and LIVERAGE-Cirrhosis. These trials will assess the effectiveness of survodutide in patients with MASH, with one focusing on those with moderate or advanced fibrosis and the other on patients with cirrhosis. The FDA's breakthrough designation is intended to expedite the review process for therapies that demonstrate substantial improvement over existing treatments during early clinical trials.

Interest in MASH treatments has been growing, particularly following the FDA's approval of the first-ever MASH therapy, Rezdiffra (resmetirom) by Madrigal Pharmaceuticals, in March. Market analysts estimate that the MASH therapy market could reach $25.7 billion in sales by 2032 across major global markets, including the US, France, Germany, Italy, Spain, the UK, and Japan.

Survodutide, a dual agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptors, was originally licensed by Boehringer from Zealand Pharma in 2011. Initially developed for treating type 2 diabetes and obesity, Boehringer holds exclusive rights to develop and commercialize the drug globally, except in the Nordic countries where marketing rights are shared with Zealand Pharma.

The LIVERAGE trial will be a placebo-controlled study involving approximately 1,800 patients with MASH and moderate or advanced fibrosis (stage II-III). The study will be conducted in two parts: part one will last 52 weeks, followed by a continuation phase lasting up to seven years. The primary goal in part one is to determine the proportion of patients achieving MASH resolution without worsening fibrosis and at least a one-point improvement in fibrosis without worsening MASH after 52 weeks of treatment. Part two will focus on the time to the first occurrence of liver-related events or all-cause mortality.

The LIVERAGE-Cirrhosis trial, also placebo-controlled, will enroll around 1,590 participants with stage 4 liver cirrhosis. The primary endpoint for this study is the time to the first occurrence of all-cause mortality or liver-related events over a period of 4.5 years.

Survodutide's main competitor is expected to be Eli Lilly’s tirzepatide, which has shown promising results in a Phase II MASH trial. Tirzepatide is already marketed under the names Mounjaro and Zepbound for treating type 2 diabetes and obesity, giving it an edge due to significant physician familiarity.

Boehringer’s proactive steps in advancing survodutide through rigorous Phase III trials could potentially lead to a significant breakthrough in the treatment of MASH, especially given the growing interest and need for effective therapies in this area. The outcomes of these trials will be closely watched by both the medical community and stakeholders in the pharmaceutical industry.