Sagimet stock doubles as phase 2b MASH trial hits primary goals, despite dropout queries

Sagimet Biosciences has eased the pain of investors who backed its IPO last year, reporting phase 2b data in metabolic-associated steatohepatitis (MASH) that sent its stock soaring. Yet, the 20% dropout rate in the drug arm and exclusion of patients from the analysis prompted questions from analysts. 

The headline finding is that denifanstat beat placebo on two key endpoints. The rate of resolution of MASH—also known as nonalcoholic steatohepatitis (NASH)—without worsening of fibrosis and with at least a two-point reduction in disease activity was 36% on denifanstat and 13% on placebo. Similarly, 52% of people on denifanstat had at least a two-point reduction in disease activity without worsening of fibrosis, compared to 20% of their peers on placebo.

On a conference call with analysts to discuss the data, University of California San Diego’s Rohit Loomba, M.D., said denifanstat “is showing very consistent effects for both MASH resolution and fibrosis improvement” and the “treatment effect delta is very strong.”

Loomba noted that other molecules have improved MASH and fibrosis in different clinical trials but declined to compare the data. Denifanstat is a FASN inhibitor, setting it apart from frontrunners such as Madrigal Pharmaceuticals’ resmetirom.

Investigators randomized 168 patients with biopsy-confirmed F2/F3 MASH to take denifanstat or placebo. The biotech’s analysis focused on a modified intent-to-treat population (mITT) of 126 participants with paired biopsies. In the denifanstat arm, 28% of the 112 randomized patients were excluded from the mITT population. In the placebo group, 20% of the 56 original participants were excluded. 

Sagimet has yet to share the ITT results but confirmed they were statistically significant. On the analyst call, Eduardo Martins, chief medical officer at Sagimet, said, “The study did hit statistical significance with a two-sided P value in the ITT analysis, and this is how the protocol was designed.” 

Twenty percent of patients on denifanstat dropped out because of treatment-emergent adverse events (TEAEs). The dropout rate in the placebo arm was 5%. The biggest imbalance in TEAEs was in skin and subcutaneous tissue disorders, which affected 22% of people on denifanstat compared to 5% of their peers on placebo.

Martins said some patients “experienced hair thinning” but “it reversed completely after down titration or discontinuation.” Sagimet is now investigating the factors that may have contributed to the cases and identified COVID-19 and medicines “known to cause alopecia, such as GLP-1 analogs and levothyroxine” as potential drivers. 

On the dropout rate, Martins said “we did expect a larger discontinuation than studies performed before the COVID pandemic.” The CMO declined to compare the dropout rate to that seen in trials of rival drug candidates, noting that “head-to-head comparisons are always difficult.” 

Sagimet shares more than doubled in early trading, jumping to $15.00 by 10.30 am ET to wipe out some of the losses it has suffered since it went public at $16 in July.

The biotech plans to move into phase 3 this year. Sagimet is “prepared to do so independently,” CEO Dave Happel told investors, but will “consider other options that may be available to us to help finance the efforts.”