Senna Alata

Progress Reported in MASH with Survodutide

Yet another GLP-1 agonist in development for obesity – survodutide – showed promising results yesterday from a phase 2 clinical trial in MASH. In case you missed the notice, MASH is the new acronym for what we used to label as NASH. We also note that MASLD has replaced NAFLD in the nomenclature alphabet soup for metabolic liver disease.

But the real news here is that we have serious prospects for better therapies in these  increasingly prevalent forms of liver disease that often come along for the ride with obesity.

A Dual Glucagon/GLP-1 Agonist

Phase 3 studies for Survodutide in obesity began last year. Boehringer Ingelheim is developing this dual agonist for both obesity and MASH indications. Its indication for treating MASH received a “fast track” designation from FDA because of the lack of good options for treating this disease.

Survodutide works to activate both GLP-1 and glucagon receptors. By comparison, semaglutide only acts on the GLP-1 receptor, while tirzepatide works on the GLP-1 and GIP receptors. The hope is that by targeting different receptors, this drug may prove to have clinical advantages. In the results for MASH, Boehringer says that 83% of patients receiving the drug saw an improvement in MASH – compared to only 18% of patients on placebo. Also impressive was the observation of a significant improvement in liver fibrosis. In this study, fibrosis was a secondary endpoint.

We will be eager to see the full results peer reviewed and published.

Intense Interest and Challenges

The path to developing meaningful advances in treatment for MASH is littered with failures. But the need is great because this disease is becoming more common as the prevalence and severity of obesity is rising. But developing a new drug to treat this condition has proved to be very tricky.

Intercept Pharmaceuticals gave it a shot a decade ago and had a clinical trial of obeticholic acid with such stunning results that it had to be discontinued for ethical reasons – to offer the drug for patients who got the placebo. Six years later, FDA rejected the application from Intercept for using this drug in MASH. Now the company is out of business, having been acquired in January for a tiny fraction of its peak stock price.

Semaglutide has had mixed results in clinical trials for MASH – one hit and one miss. Tirzepatide recently had good news from topline results in this disease. Perhaps even more promising is a drug called resmetirom. Earlier this month, NEJM published results for this drug showing that it both helped with resolving MASH and improving fibrosis scores. We also note that resmetirom had no effect on body weight.

So, yes, it is good news that survodutide is showing good results for treating MASH. But getting to an FDA approval will be the real test.

Click here, here, and here for more on the topline results with survodutide. For the NEJM paper on resmetirom, click here. To learn more about the prospects for new drugs to treat MASH, click here, here, here, and here.

Senna Alata, photograph by Iezalel Williams / flickr. Note that senna is sold as an ingredient in laxative preparations and was once promoted for treating liver problems. Now scientists know it can be toxic to the liver.

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February 27, 2024