Maze Therapeutics has revealed topline phase 2 data for its lead kidney disease candidate that has analysts heralding its “best-in-class potential.”
The once-daily oral small molecule APOL1 inhibitor, MZE829, cut levels of excess protein in the urine by an average of 35.6% among 12 patients after 12 weeks of treatment, Maze reported (PDF) on March 25, which the company called “clinically meaningful.”
Analysts from Mizuho agreed, noting MZE829 surpassed the generally accepted 30% benchmark and could become best-in-class.
“There is a drug here that is likely approvable (and commercial),” the analysts wrote.
Investors had a very different reaction, with many racing for the exits on Wednesday. By 11:15 a.m. EDT, Maze’s stock fell roughly 38% to around $30 per share.
The open-label phase 2 Horizon trial’s primary endpoint is safety, which Maze said so far looks good. There were no serious adverse severe events or treatment-related adverse events, with the most common side effects being headache and diarrhea. One patient discontinued treatment just before the week 12 visit due to nausea, according to the release.
As the phase 2 study continues to enroll, Maze is also now planning to advance MZE829 into a pivotal trial, the biotech said.
Maze’s focus is on a broad population of patients with APOL1-mediated kidney disease (AMKD), a genetic form of kidney dysfunction caused by certain variants of the apolipoprotein L1 (APOL1) gene.
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The Horizon trial is enrolling patients both with and without Type 2 diabetes, and patients with diabetes generally saw lower protein reductions than those without.
“This was the first clinical data showing any signal in diabetes,” Maze CEO Jason Columa, Ph.D., said during a March 25 call with investors. “As we think about continuing to enroll patients, we’re going to learn a lot more. This just definitely moves the field forward.”
“We have a potential medicine for broad AMKD,” Maze Chief Medical Officer Harold Bernstein, M.D., Ph.D., added during the call. Further data from Horizon will now be used to refine the patient population targeted in the upcoming phase 3 trial, he said.
During the call, many questions focused on MZE829’s competitiveness with Vertex’s APOL1 inhibitor inaxaplin. Vertex’s earlier phase 2 study of inaxaplin focused on a subset of AMKD patients with focal segmental glomerulosclerosis (FSGS), a severe type of kidney scarring that can lead to kidney failure.
Vertex’s trial showed around 43% protein urine reduction in 13 patients with FSGS, the Mizuho analysts pointed out, while MZE829 produced an about 62% average reduction in four similar patients. Vertex is now running a larger phase 2/3 trial of inaxaplin in patients with APOL1-mediated kidney disease, including some with diabetes, with phase 2 data set to read out later this year.
While reiterating that MZE829 has delivered “a very good dataset,” Mizuho analysts explained Maze’s tumbling share price as Wall Street getting hung up on the results in the non-FSGS patients, including those with and without diabetes. “But the fact remains that [MZE829] is showing an effect in all of these,” the analysts wrote.
Analysts from Leerink Partners agreed, calling the mass selloff an “overreaction.”
“We understand the desire to compare assets, though given the differing patient populations, this is an apples to oranges comparison, and we would caution against overinterpretation,” they wrote. “At first glance, the trial exceeded the bar set by management and seems competitive to other assets in development.”
