The Advantage for the First Mover in NASH is Limited, says Genfit

After we reviewed NASH earlier this year, Genfit’s CSO, Dean Hum, came to speak at Refresh about his company’s strategy in the space.

As CSO of Genfit, Dean Hum coordinates the company’s R&D efforts to be first to market in NASH, which represent an untapped market of €37B. The company is counting on its lead candidate, Elafibranor, to take the first bite out of the space. He came to speak about the space and Genfit’s strategy at Labiotech’s Refresh in June.

Since his company decided to go into NASH in 2012, Hum now sees the NASH space as defined by “two leading companies — Genfit and Intercept — with programs in Phase III.” But while much might be made of being the first mover, Hum said that “it’s important to remember its high prevalence.” Up to 12% of adult US population has NASH according to one study, and “that means a huge market.”

Moreover, “it’s a multifactorial disease, so it’s quite complex. With that market size and these different aspects, I think there’s going to be room for many different approaches,” Hum told the audience. The first stage, in which fat accumulates in liver cells, is the metabolic stage. The accumulation leads to inflammation, at which point the disease is labeled hepatitis.

This pathology, in turn, leads to fibrosis which can turn into life-threatening cirrhosis: without a liver transplant, a patient may die from liver failure or liver cancer. Many different programs target the final fibrotic stage, but “you have to realize that the underlying cause, NASH, is still there,” said Hum.

So Genfit, for its part, targets inflammation. Elafibranor, a dual peroxisome proliferator-activated receptor (PPAR) agonist, aims to resolve NASH entirely by eliminating necroinflammation without worsening fibrosis. Thus, the company aims to “resolve NASH without worsening of fibrosis… If you can resolve it, then you’ll see a clinical benefit,” as Hum described. “We aim to treat these patients and prevent them from progressing to clinical events,” like cirrhosis and mortality as well as cardiovascular events. “The leading cause of mortality is cardiovascular events and disease, not so much liver events,” he noted.

But how do you design a preventative trial? Hum said Genfit’s strategy is to “target the population of NASH patients who are the highest risk of progressing to clinical events” meaning mortality, cirrhosis, mortality. Then, “the regulatory pathway is to include them in a trial and set the primary endpoint showing that you have a significant impact on the histology of the liver and fewer clinical events, and if you hit it, you’ll get registration and approval.”

Given the fatal risk associated with NASH, both the FDA and the EMA have put the disease on its list of priorities. Further, groups like the Liver Forum are coordinating efforts to forge a path to market for drugs, since there is no therapy currently available. Treatment paradigms have been limited to sparing use of Vitamin E and lifestyle management.

But this approach “is the baseline counseling that we should all take into account — we all know it’s not enough,” said Hum. “As we see in other metabolic diseases, there’s a small number of patients in other metabolic diseases who are able to maintain that lifestyle.”

“The point is not so much who’s going to make it to the market first — I think the first mover advantage is quite limited — I think it’s important to think about…the profiles of different drugs when they get to the market?” Hum remarked, noting that they will be differentiated in terms of safety, efficacy, tolerability.

He continued, “What’s clear is that there is a large unmet need, and what’s nice is that things are coming together — regulatory agencies are on board to provide a path forward by recognizing it as a severe disease; different drug companies working on approaches; pipeline has come to a certain maturity ; more disease awareness right now.”

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