The landscape of Nonalcoholic Steatohepatitis (NASH) appeared promising with Madrigal Therapeutics taking steps toward treatment approval. However, this optimism was dampened recently by Akero Therapeutics’ phase 2b setback. NASH, a challenging disease to address, has eluded effective treatments despite efforts from various companies.
Akero’s FGF21 analog, Efruxifermin (EFX), aimed to reduce fibrosis in cirrhotic NASH patients, following its earlier success in less advanced cases. However, the treatment fell short in the more advanced patient group. Some analysts suggest that the disease may have progressed too far for the treatment to be effective, drawing parallels with conditions like Alzheimer’s or cancer. Additionally, Akero’s interim analysis might have been too premature at 36 weeks, given that the total study period is 96 weeks.
On a more positive note, Leerink Partners found merit in the results, considering the advanced disease state in question. They noted positive aspects in the 36-week timeframe, despite the disappointing outcome on the primary fibrosis improvement endpoint. This was hailed as the strongest efficacy dataset in this challenging patient population thus far.
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While Akero’s stock plummeted from $48.58 to $17, other companies in the NASH field were not immune to the repercussions. Madrigal’s shares, which reached $150, experienced a drop to $144, and 89bio’s stock dipped from $15.51 to $9.38.
Mizuho analysts expressed concerns about the setback’s potential impact on investor interest in NASH, given the recurring late-stage disappointments in the field.
It’s worth noting that 89bio’s lead asset, Pegozafermin, shares a mechanism of action with EFX, which contributed to its decline alongside Akero. Both target the metabolic hormone FGF21, with the aim of reducing liver fat, preventing new fat formation, and lowering triglycerides while reducing fibrosis.
Leerink downplayed the stock reactions for Akero and 89bio, emphasizing that the FGF21 class still holds promise in advanced fibrotic and compensated cirrhotic NASH, especially with the clear NASH resolution benefits demonstrated in this patient group.
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Viking Therapeutics and Terns Pharmaceuticals, other players in the NASH race, experienced varying market reactions, with some remaining stable. Mizuho pointed out that Tern’s TERN-501, a THR-beta agonist with a different mechanism of action, doesn’t provide direct insights into this situation and is not currently being studied in such advanced patients.
The NASH landscape also faces competition from GLP-1 drugs that have shown potential in reducing weight and addressing early NASH cases. However, they don’t address the crucial issue of fibrosis. The future might involve combination approaches to tackle all aspects of this complex disease.
Meanwhile, the FDA is considering Madrigal’s resmetirom for approval, which could become the first NASH treatment on the market if approved.
