Intercept Presents Encouraging NASH Results

It’s been a long road for Intercept Pharmaceuticals to develop an important advance for treating NASH (non-alcoholic steatohepatitis). Five years ago this little startup company shocked the world when a monitoring board stopped a placebo-controlled study because their drug (obeticholic acid or OCA) had worked so well. A final round of 64 liver biopsies were unnecessary and would have been unethical.

Now we have encouraging interim results from a bigger ongoing study.

Five Years Later

But in between these two times, it’s been a bumpy road. The discontinuation of the FLINT study caused the stock of this little startup to zoom up to a value of $1.4 billion. Later, though, with the publication of the full study results, it plummeted to less than half that value. The results were a bit of a mixed bag. Impressive efficacy measured by cellular changes in the liver on one hand. However, the long-term safety and clinical benefits were not so certain.

Thus, this week’s news is encouraging. The interim results are from an ongoing study called REGENERATE. These are 18-month results, but target date for full completion is not until 2022.

In this interim analysis, we have the first positive results for a drug to treat the fibrosis in NASH. Significantly more of the patients receiving 25 mg of OCA had improvements in liver fibrosis compared to placebo patients. On another endpoint, resolution of NASH, the drug was not significantly better than placebo in this interim analysis.

More Work to Do

On many fronts, it’s clear that these folks have more work to do. The investigators are excited. When Zobair Younossi presented the results, he called it a “watershed moment” because it is the first randomized study to show efficacy.

A more dispassionate view came from Phillip Newsome, a hepatology professor at the University of Birmingham:

This is an important step forward. It is the first study that shows effectiveness in treating NASH. There is a signal there that shows effect against fibrosis, which is the most important thing. It will be interesting to see how that evolves further with more prolonged treatment. I think I would use it now in patients with Stage F3 fibrosis. I would hope and expect that the benefits will increase with this treatment and future treatments.

On the other hand, you can expect biases about people with obesity and NASH to come into play. Hepatologist Sidney Barritt offers a bit of this, saying:

This isn’t just a medical issue, it’s a social and moral imperative. The burden of this disease is going to bankrupt our healthcare system.

There’s a need for pharmacological intervention, but taking a pill absolves us of doing the things we need to do, like staying active and eating healthy. We don’t know how this lifetime drug will work in the real world.

Does this sound familiar? To us it sounds like a perfect expression of bias. Some people seem to regard effective treatments for obesity as an “easy way out” and a moral hazard.

As long as attitudes like this lurk in the medical profession, we have a lot of work to do.

Click here and here for more on the presentation of these results. For more on the travails of Intercept Pharmaceuticals, click here.

1953 Nash-Healey Roadster, photograph © Tom Hilton / flickr

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April 12, 2019