Shares of Maze Therapeutics, a San Francisco-area biotechnology company, fell over 30% Wednesday despite positive clinical trial results for a progressive kidney disease drug that could potentially compete with a rival therapy from Vertex Pharmaceuticals.
Maze said that, in a mid-stage trial, treatment with its experimental drug, “MZE829,” led to a “clinically meaningful” reduction of protein levels in urine by an average of almost 36% in people with a kidney disease caused by mutations in a gene called APOL1. Maze said it will continue enrollment for its Phase 2 trial and plans to meet with regulators to advance MZE829 into pivotal testing for AMKD, or APOL1-mediated kidney disease.
Full results from the Phase 2 trial will be presented at a future medical conference, Maze added.
Two variants in the APOL1 gene can lead to different types of kidney illness — including AMKD, a rapidly progressive form of “proteinuric” kidney disease marked by high levels of protein in urine. No approved treatments specifically target AMKD; physicians instead rely on standard care for chronic kidney disease.
Maze has been aiming to bring its own drug against AMKD that can compete with Vertex, which has become a leader in the space with its own candidate.
In its Phase 2 study titled “Horizon,” Maze enrolled 15 trial participants with AMKD who had the APOL1 high risk genotype. Across enrollees, seven had been diagnosed with diabetes, and of the remainder, five had a rare chronic kidney condition called focal segmental glomerulosclerosis, which causes scarring.
All 15 participants were included in the primary endpoint, which focused on safety and tolerability, while 12 were evaluated for efficacy.
After 12 weeks, Maze said its once-daily oral APOL1 inhibitor reduced levels of protein in the urine by an average of 35.6% across those dozen participants. In patients with FSGS, MZE829 led to an average reduction in protein levels of 61.8%, while those with AMKD without diabetes experienced an average reduction of 48.6%.
Mizuho Securities analyst Salim Syed said in a note to clients Wednesday that the drug is “showing best-in-class potential in broad AMKD,” and that its 36% protein reduction is above the generally accepted benchmark and “likely approvable.”
Joseph Schwartz, analyst at the firm Leerink Partners, noted investors might be comparing Maze’s drug to Vertex’s inaxaplin. Specifically, slides Maze presented indicated patients with diabetes might not have responded as strongly to its treatment as other study participants. Schwartz cautioned against overinterpreting those findings given the small sample size, as well as underlying differences between the studies of the two drugs.
“We understand the desire to compare assets, though given the differing patient populations, this is an apples to oranges comparison,” he wrote in a note to clients Wednesday, calling the stock sell-off a “vast overreaction” to the data.
