The Tortured Pathway for a New NASH Treatment

The Tortured Pathway for a New NASH Treatment

It’s tough getting good information these days. Good, factual information. Everybody wants to spin it. That’s undeniable in public policy. But it also seems to be true in drug development. Yesterday, the FDA definitively rejected an application from Intercept Pharmaceuticals for a new drug to treat NASH – nonalcoholic steatohepatitis. The company was shocked. Its CEO said they had no clue this was coming. But this is only the latest twist in the tortured pathway for a new NASH treatment.

And frankly, we wonder how the company could not see this coming. If everyone is doing their job, regulatory surprises like this are indeed rare.

A Breakthrough Six Years Ago

The saga of this new NASH treatment burst into headlines more than six years ago. Intercept Pharma was a tiny company. Only 45 employees. Its stock value quadrupled to $5.3 billion instantly when a trial of obeticholic acid halted because the results were so good.

Ordinarily, when researchers stop a blinded study like this, that means that everyone in the study should be getting the study drug. It would be unethical to withhold it. So, that typically leads to the company behind the drug working with FDA for an accelerated path to the market.

Six years later, no such thing has happened. FDA has said specifically that it cannot grant an accelerated approval. Not that a six-year delay between “exciting” clinical results and FDA action seems very accelerated. It simply makes no sense.

What’s Up?

The approval of new drugs should be objective and formulaic. You demonstrate safety in phase 1 studies and show that they work in phase 2. Then in phase 3, you show that the benefits outweigh the risks. Submit a tidy NDA to FDA and if all of it checks out, you get an approval within a year. Six months if you have a breakthrough.

But that’s clearly not what happened here. We can’t help but wonder why. Did the company screw up in some way that is not obvious? Clearly that’s not the story Intercept is telling. Its CEO seems to be pointing fingers at FDA for “evolving expectations.” That’s a subtle way of saying the FDA is moving the goalposts.

Reservations About Treating NASH?

It is possible that this small biotech isn’t real good at navigating issues with FDA. It’s also possible that FDA has reservations about approving drugs for NASH, which is most often a result of untreated obesity. Maybe the agency is picking up such reservations from external advisors. A hint of this possibility shows up in a recent Lancet editorial:

We cannot simply treat our way out of a burgeoning public health crisis that, at its root, is caused by malnutrition. Societal change is needed to address the obesogenic environment, social determinants of health, and failing food systems. Preventive measures are essential if we are to halt the tide of incident cases of NAFLD and NASH, and must begin at an early age.

That kind of declaration is something we once heard all the time about obesity. It suggests a bias that these people (with NASH) are not worth the bother of treating their disease. It should have been prevented. That attitude, whether it’s implicit or said aloud, is infuriating and unacceptable.

Click here, here, and here for more on the FDA rejection of obeticholic acid for NASH. For a report of the phase 3 trial results, click here.

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June 30, 2020