"Reducing Liver Fat Is Not Enough": Limitations of MASH Preclinical Studies Present New Challenge for Domestic Drug Development
- Current Focus: Liver Fat / Enzymes
- New Requirement: HCC Suppression
- Observation: > 54 Weeks
- Market Value: 40 Trillion Won
- Risk: Increased Costs
There have been calls to fundamentally reassess the preclinical approaches to developing new drugs for MASH (Metabolic Dysfunction-Associated Steatohepatitis), a field where global pharmaceutical companies have invested trillions of won but have repeatedly failed. Experts argue that, beyond simply reducing liver fat or improving liver enzyme levels, it is necessary to verify the potential for suppressing hepatocellular carcinoma (HCC) starting from the preclinical stage.
Analysts have also pointed out that the current preclinical methods, which artificially induce the disease in a short period, make it difficult to meet such criteria. There are concerns that the preclinical designs commonly used by domestic pharmaceutical and biotech companies have limitations in predicting clinical success.
European Research: Short-Term Models Fail
According to the bio industry on February 3, a European research team supported by Boehringer Ingelheim recently published a paper in the international journal 'Nature Reviews Gastroenterology & Hepatology,' arguing that widely used short-term preclinical models cannot accurately predict the clinical success of MASH therapeutics.
The research team identified excessive reliance on short-term indicators such as liver fat content or enzyme levels as a cause of failure. They insist that the entire progression of MASH to liver cancer should be replicated, and it must be confirmed whether the drug can suppress disease progression itself.
Leading drug candidates, including Gilead Sciences’ Selonsertib, have repeatedly failed in Phase 3 clinical trials. While efficacy was confirmed in preclinical animal studies (typically 8 to 12 weeks), the same results could not be replicated in humans.
New Barrier: 54-Week Observation
For successful new drug development, the researchers highlighted long-term observation and acquisition of liver cancer data as key preclinical requirements. They emphasized that it is necessary to observe for more than 54 weeks, equivalent to half the lifespan of laboratory mice.
The preclinical criteria suggested by the research team could become a new barrier to entry for domestic biotech companies. This is because the need for long-term observation of more than a year would extend development timelines and significantly increase costs. Additionally, the requirement to confirm the occurrence of liver cancer raises the risk of failure.
Domestic Cases: Hanmi Pharmaceutical and D&D Pharmatech
In fact, there are reportedly still few domestic cases where such preclinical designs have been fully applied.
- Hanmi Pharmaceutical: Its candidate epinopegdutide, licensed out to Merck (MSD), did not undergo long-term observation exceeding 54 weeks during the preclinical stage.
- D&D Pharmatech: Candidate DD01 also did not include long-term observation. The company focused on the F2-F3 patient group (intermediate fibrosis) and used a representative MASH animal model over about eight weeks.
Industry Perspective
Domestic companies agree with the overall direction of the preclinical criteria proposed by the research team. However, they state that in actual development, they have no choice but to prioritize the speed of clinical entry and indication strategy.
— Hanmi Pharmaceutical Representative
