Akero Challenges Madrigal in MASH Treatment Arena

The pharmaceutical industry has recently witnessed a significant development with the FDA's approval of Rezdiffra, a drug by Madrigal Pharmaceuticals, for treating metabolic dysfunction-associated steatohepatitis (MASH). This approval marks a milestone for patients who previously had no therapeutic options for this condition. However, Akero Therapeutics is emerging as a potential competitor with its Phase IIb HARMONY trial results for efruxifermin (EFX), showing promising effects on patients with F2-F3 liver fibrosis.

The FDA's criteria for MASH drug approval include a one-stage improvement in fibrosis without MASH worsening. In the HARMONY trial, a substantial percentage of patients treated with EFX demonstrated such improvement, outperforming the placebo group. Although the lower dosage of EFX did not reach statistical significance, the higher dosage did, suggesting its potential as a competitive therapy.

Akero's approach to targeting patients with more advanced liver fibrosis could provide more robust evidence for EFX's efficacy in reducing liver fat, as these patients exhibit hepatic scars not present in earlier stages. Moreover, the trial's design, which only included patients who strictly adhered to their treatment regimen, could enhance the perceived efficacy of EFX.

Despite Madrigal's Phase III data for Rezdiffra being limited to 52 weeks, Akero's drug has shown long-term benefits, which could be a deciding factor for alternative treatments. However, Akero's trial has not included MASH patients with F1 liver fibrosis, positioning Rezdiffra as the preferred first-line treatment for early-stage MASH, with EFX possibly serving as a second-line option.

The administration methods of the two drugs also differ; EFX requires a weekly subcutaneous injection, while Rezdiffra is an orally administered tablet. This difference could impact cost and quality control considerations. Furthermore, the small sample size in Akero's trial raises questions about the statistical robustness of its results compared to Madrigal's larger study.

While Akero's preliminary data is encouraging, the real-world effectiveness of EFX is yet to be determined. The MASH treatment market is expected to evolve rapidly, and the competition between these two therapies will be a key area to monitor in the near future.