After phase 2 flop, Novo Nordisk says its NASH work is 'still very much on track'

Nonalcoholic steatohepatitis (NASH) has been among the most elusive targets in the biopharma industry in recent years. And just as the condition is growing in an increasingly obese world, so too is the roster of companies trying and failing to develop a remedy.

Novo Nordisk is hoping to keep its name off that list, but a midstage trial failure raises new concerns for its prospect. In a phase 2 trial of its highly successful Type 2 diabetes drug Ozempic (semaglutide) against NASH, the treatment was outdone by placebo by a wide margin.

While this trial proved a disappointment, a Novo spokesman said semaglutide's development in NASH is "very much still on track."

In the study of 71 NASH patients with compensated cirrhosis (the F4 stage of the disease), only 10.6% of those who received a weekly 2.4 mg dose of semaglutide saw an improvement in liver fibrosis coinciding with no worsening of NASH. The figure for those on placebo was 29.2%.

As a secondary endpoint, 34% of patients on semaglutide saw a resolution of NASH—which means improvement in liver inflammation and liver cell ballooning—versus 20.8% on placebo.

Investigators presented the results at the European Association for the Study of Liver annual meeting.

Novo isn't dissuaded by the results and still sees promise for semaglutide in NASH.

"The development of semaglutide in NASH is very much still on track and actually in phase 3," a Novo Nordisk spokesman said in an email. "In August 2020, the FDA granted breakthrough therapy designation for semaglutide in NASH, and in April 2021 we initiated the phase 3 program Essence."

Meanwhile, Novo has multiple development tracks underway for the drug in NASH F4, he added.

Novo Nordisk had high hopes for semaglutide in the indication when it released positive results of another phase 2 trial two years ago. In that study, of 56 patients with a less severe form (F2 and F3 stages) of NASH, 59% saw disease resolution versus 17% in the control arm.

Now, the company pressing ahead in a field that has taken multiple victims in recent years.

Intercept Pharmaceuticals showed promise in a run at NASH with its obeticholic acid treatment before getting a rejection from the FDA. The U.S. regulator concluded two years ago that the benefits of the drug were uncertain and not worth the risks it presented.

Around the same time in 2020, Genfit dropped its phase 3 trial in NASH after flunking an interim analysis.

And just last year, Allergan and NGM Bio bailed on their NASH attempts, joining other companies large and small that have flopped in the disease including CymaBay, Conatus, Shire, and Gilead.

A golden opportunity awaits for whoever can conquer NASH. The market opportunity has been estimated to be as high as $35 billion.