NASDAQ:MTVA
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Business Update
Compelling Results for DA-1241 in Phase 2a MASH Trial
On December 18, 2024, MetaVia Inc. (NASDAQ:MTVA) announced positive topline results from the 16-week Phase 2a clinical trial of DA-1241 in patients with presumed metabolic dysfunction-associated steatohepatitis (MASH). The trial had two parts: in Part 1, patients were randomized in a 1:2:1 ratio into three treatment groups (DA-1241 50 mg, DA-1241 100 mg, or placebo). In Part 2, patients were randomized in a 2:1 ratio into two treatment groups (DA-1241 100 mg + 100 mg sitagliptin, or placebo). The primary efficacy outcome was the change in alanine aminotransferase (ALT) levels from baseline at week 16.
The following table gives the least square mean ALT values for each treatment group at baseline, 4 weeks, 8 weeks, and 16 weeks. DA-1241 100 mg treatment resulted in a statistically significant decrease in ALT at week 4 and week 8 and was very near statistical significance at week 16. The combination therapy of DA-1241 and sitagliptin did not show a greater effect than monotherapy DA-1241. The company has imagined that DA-1241 will ultimately be used as a combination therapy, however from this data it is apparent that combination will not be with a DPP-4 inhibitor.
In addition to the change in ALT, a number of secondary efficacy endpoints were evaluated including reductions in controlled attenuation parameter (CAP; measure of fat in the liver):
and hemoglobin A1c (HbA1c):
Lastly, DA-1241 was well tolerated during the study, with only 34.6% of participants reporting any treatment emergent adverse event (TEAE), compared to 28.1% of placebo-treated patients. In addition, there were no serious treatment related adverse events and no participants on DA-1241 discontinued due to a TEAE.
While it is always difficult to do between-trial comparisons, we still feel it is important for investors to be aware of how DA-1241 compares to other MASH therapies. Rezdiffra® (resmetirom) was approved in March 2024 for the treatment of MASH based in part on the results of a 36-week Phase 2 trial (Harrison et al., 2019) and a 52-week Phase 3 trial (Harrison et al., 2024). The following table provides a comparison between the results for DA-1241 at 16 weeks and resmetirom at either 12 weeks (for change in ALT) or 52 weeks (for change in CAP and HbA1c). The results show that treatment with DA-1241 for 16 weeks led to a greater change in ALT, a similar change in CAP, and a greater decrease in HbA1c, all of which are indicative of the drug having positive liver-specific effects. In addition, there were fewer treatment emergent adverse events (TEAEs) reported for DA-1241. Overall, we believe the key takeaway for investors is that DA-1241 is showing positive liver-specific effects over a relatively short treatment period that compare favorably to an already approved MASH therapy.
Conclusion
We’re very encouraged by the results seen with DA-1241 100 mg in the Phase 2a trial in patients with presumed MASH. The drug was well tolerated and led to positive changes in multiple liver-specific parameters. In addition, the large decrease in HbA1c over such a short treatment period is very encouraging and could prove to be a key differentiating feature of the drug. We look forward to additional data from the trial being reported in 2025, including MRI-PDFF results.
The stock reacted negatively to the data release and there are likely multiple reasons for this, including the fact that the combination arm of DA-1241 and sitagliptin did not show as strong an effect as DA-1241 monotherapy. However, we don’t believe investors should focus on this as it is unlikely to offer any read-through to potential future combination therapies that the company may pursue. MetaVia is actively looking to form a partnership, collaboration, or licensing deal to advance DA-1241 into a late-stage MASH trial in combination with another agent, and while we are unsure what form that will take it is unlikely to be with a DPP-4 inhibitor. We anticipate an update from the company on the DA-1241 program following the full analysis of the data set. Following these results, we have slightly increased the probability of approval for DA-1241 in our model, which has increased our valuation to $23 per share.
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