Besting Vertex Pharmaceuticals’ kidney disease asset wasn’t enough to impress Wall Street, which appears to be “getting hung up” with the broad population data in Maze Therapeutics’ trial, according to Mizuho.
Maze Therapeutics was down more than 30% Monday afternoon after reporting topline results from a Phase 2 trial of its candidate for APOL1-mediated kidney disease—despite besting a Vertex Pharmaceuticals contender in a small subgroup of patients.
Treatment with MZE829, an oral, dual-mechanism APOL1 inhibitor, led to a 35.6% mean reduction in proteinuria as measured by urinary albumin-to-creatinine ratio (uACR) at 12 weeks in a broad set of patients with APOL1-mediated kidney disease (AMKD), a result Maze called “clinically significant” in its Wednesday press release. Additionally, 50% of treated patients saw a greater than 30% reduction 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 in a statement.
While the results appear on the surface to be something to celebrate, the small sample size could be to blame for the biotech’s cratering shares, Truist Securities told investors in a Wednesday note.
The HORIZON trial enrolled 15 patients with broad AMKD carrying the APOL1 high-risk genotype, including those with and without diabetes. A subgroup of patients without diabetes but with severe focal segmental glomerulosclerosis (FSGS) saw a 61.8% reduction in uACR—a result Truist said “exceeds the signal reported for Vertex’s inaxaplin in a similar population.”
This is “supportive of MZE829’s dual mechanism of action and potential best‑in‑class profile,” the analysts concluded.
However, “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,” Truist said. The small sample size “limits interpretation,” the analysts added.
Mizuho Securities agreed with this consensus, writing, “Pound for pound, the [MZE829] data presented today looks better than [inaxaplin] in cross-trial comparison.” While MZE829 led to a 62% reduction in uACR, inaxaplin elicited only a 43% reduction in FSGS patients in a Phase 2a trial, according to Mizuho. Notably, a 2023 publication of the Phase 2 results in The New England Journal of Medicine has this metric at 47.6% for inaxaplin. Vertex is currently testing the asset in a Phase 2/3 trial.
Where Wall Street is “getting hung up,” Mizuho said, is with the numbers in the broad population. “But the fact remains that [MZE829] is showing an effect in all of these [cohorts]; none were zeros,” the analysts continued. “So to take broad AMKD PoS [probability of success] down to zero essentially seems overdone.”
