Semaglutide for NASH: Disappointing Results

Nonalcoholic steatohepatitis – NASH – has yet again handed drug researchers disappointing results, this time in a study of semaglutide. Researchers presented this phase 2 study at the International Liver Congress in London last weekend. The whole point of a phase 2 study is to see if a drug works for a specific purpose. On the primary endpoint in this study, semaglutide failed. The primary goal was to improve liver fibrosis without worsening NASH.

That simply didn’t happen in this trial. In fact, only 11 percent of patients receiving semaglutide met that endpoint, while 29 percent of the placebo patients did. This difference was not significant, but it was running in the wrong direction altogether. This was a study of patients with advanced liver fibrosis – a stage known as F4.

A Head-Scratching Result

This is a puzzling result. Trying to put a good face on these clearly disappointing findings, Rohit Loomba presented them and said:

“Although the primary endpoint was not met, once-weekly semaglutide 2.4 mg appeared safe and was well-tolerated in this 48-week trial in patients with NASH and compensated cirrhosis.”

Last year a different phase 2 study with the same drug for the same disease yielded much more positive results. That was a bigger study with earlier stage disease than the patients had in the new study. In last year’s study, the primary endpoint was different – resolution of NASH with no worsening of liver fibrosis. For that primary endpoint, semaglutide was indeed effective. However, it’s worth noting that researchers did not see an improvement in fibrosis in that earlier study either.

Proceeding Carefully

Surprises in research present an opportunity for learning. Novo Nordisk is moving ahead with development of semaglutide for NASH despite these disappointing results. But they are taking in the learning from this and other studies. Late last year, the head of development at Novo Nordisk, Martin Holst Lange, told analysts:

“A consequence of these results, we have decided that semaglutide will be further developed for F4 cirrhosis patients as part of combination therapy only.

“It’s important to mention, and as previously discussed in Q2, that semaglutide in monotherapy appears to be a very effective and potentially interesting treatment for patients with NASH F2 and F3. And this is currently being investigated in Phase III under an FDA breakthrough designation.”

So maybe the glass is at least half full for semaglutide in treating NASH. This is a hard disease where many other drugs have failed.

Click here for the abstract of this latest study (page 35). For further reporting, click here, here, and here.

Glass and Lemon, painting by Kuzma Petrov-Vodkin / WikiArt

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July 2, 2022