Maze Therapeutics reported on Mar. 25 that its stock dropped by more than 30% following the release of topline results from a Phase 2 trial of its oral, dual-mechanism APOL1 inhibitor, MZE829, for APOL1-mediated kidney disease (AMKD).
The data matters to patients and investors because it could affect future treatment options for AMKD, a condition with limited therapies. The company said MZE829 led to a mean reduction of 35.6% in proteinuria at 12 weeks as measured by urinary albumin-to-creatinine ratio (uACR), with half of treated patients experiencing more than a 30% drop in uACR.
“Based on the data shown today, as well as genetics data derived through our Compass platform, we believe that MZE829’s dual mechanism approach has the potential to address the unmet need in AMKD patients,” Maze Chief Medical Officer Harold Bernstein said.
The HORIZON trial included only 15 patients carrying the APOL1 high-risk genotype. Among those without diabetes but with severe focal segmental glomerulosclerosis (FSGS), there was a reported reduction in uACR of 61.8%. Analysts at Truist Securities said this result “exceeds the signal reported for Vertex’s inaxaplin in a similar population.” However, they also noted that "with efficacy appearing most robust in a small, severe FSGS subset, there are some questions around the breadth of therapeutic impact for APOL1 inhibitors in AMKD, which we believe is contributing to share weakness this morning.”
Mizuho Securities agreed with these concerns about sample size and generalizability but pointed out that "pound for pound, the [MZE829] data presented today looks better than [inaxaplin] in cross-trial comparison." While MZE829 showed up to a 62% reduction in uACR among certain subgroups compared to Vertex's drug's reported range between approximately 43-48%, analysts cautioned about interpreting broad population numbers due to limited sample size.
Looking ahead, both Maze and Vertex continue testing their respective drugs further. As analysts debate next steps and implications based on these early results and small patient groups studied so far, Bernstein maintains optimism about MZE829’s potential role for people living with AMKD.
