CT Scan of Thorax, Liver Window

A Little More Detail on Tirzepatide in MASH at EASL

On the opening day of the EASL Congress in Milan, we got a peek at more details on the results of the phase 2 study of tirzepatide in MASH (metabolic dysfunction associated steatohepatitis). The study, called SYNERGY-NASH, will be the subject of a late-breaking presentation on Saturday at the meeting.

But the release of the study abstract was enough to unleash a good bit of chaos and confusion about what lies ahead in the treatment of MASH. The results of the SYNERGY trial were good. Yet it isn’t clear if Lilly will go all out for pivotal trials and FDA approval for tirzepatide in MASH.

Meanwhile, Madrigal Pharmaceuticals saw its share price tumble sharply on this news. The company makes resmetirom, the first and so far only treatment approved for MASH.

The Results

The news in these results was that fibrosis (liver scarring) improved more with tirzepatide than placebo. This was a secondary goal, perhaps reflecting the fact that reducing fibrosis with tirzepatide was thought to be an ambitious goal. The primary goal of the study was to show tirzepatide could help to resolve MASH without any worsening of fibrosis. The study met that goal, too.

Authors of the study concluded:

“Tirzepatide treatment for 52 weeks was more effective than placebo in achieving MASH resolution without worsening of fibrosis. Fibrosis also improved with tirzepatide treatment but without an apparent dose-response effect. Larger and longer trials are needed to further assess the efficacy and safety of tirzepatide for treatment of non-cirrhotic MASH.”

The Landscape

Despite these good results, Lilly has not yet said the company will plunge ahead with those larger and longer trials. In fact, Lilly’s Chief Scientific Officer, Dan Skovronsky, said earlier this year that retatrutide might yield better results in MASH than tirzepatide.

The competition for a home run in MASH is intense because the unmet medical need is great. So it might make sense for Lilly to invest carefully in the strongest candidate for this indication. Madrigal already has their drug approved. On Tuesday, Viking Therapeutics announced that they are seeing good results on fibrosis with their drug for MASH, VK2809.

The Need and the Challenge

The unmet medical need for treatment of MASH and MASLD is great. These conditions are now the leading cause of advanced chronic liver disease, including liver cancer. Current options for treating them are limited. Because of this great need, the investment in drug development is growing. Before resmetirom won FDA approval, many other companies saw their development programs for these conditions fail.

So the stakes are high and successful competitors expect they will reap big rewards. This will be a very interesting space to watch.

Click here for the tirzepatide abstract from the EASL Congress, here and here for further reporting. Find additional perspective here on the need for better approaches in MASLD and MASH.

CT Scan of Thorax, Liver Window, image by Ptrump16, licensed under CC BY-SA 4.0

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June 6, 2024

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