Vivoryon Therapeutics is pivoting its development strategy for varoglutamstat, an investigational oral glutaminyl cyclase (QPCT/L) inhibitor, after its Phase IIa VIVA-MIND trial failed to demonstrate efficacy in early Alzheimer's disease. The trial, like the previous VIVIAD study, missed its primary endpoint of showing a statistically significant difference in Clinical Dementia Rating – Sum of Boxes (CDR-SB) scores between varoglutamstat and placebo.
The VIVA-MIND trial (NCT03919162) was a double-blind, placebo-controlled study that investigated a 600mg twice-daily (BID) dose of varoglutamstat in patients with early Alzheimer's. Key secondary endpoints, including Cognitive Function Composite 2 (CFC2) and Alzheimer's Disease Assessment Schedule-Cognitive Subscale (ADAS-Cog) 13, also were not met. The results align with those from the earlier VIVIAD trial (NCT04498650).
Despite the disappointing Alzheimer's outcomes, the VIVA-MIND trial revealed a significant improvement in kidney function among patients treated with varoglutamstat. Specifically, there was a statistically significant increase in estimated glomerular filtration rate (eGFR) of >4ml/min/1.73m² compared to placebo (p<0.001).
"All results support the development of varoglutamstat as a convenient oral therapeutic in diabetic kidney disease," said Vivoryon CEO Frank Weber. He added that varoglutamstat has potential across a range of other kidney diseases, including rare conditions like Fabry disease and Alport syndrome.
The company's stock prices initially responded positively to the kidney function data, with a 43.3% increase on December 9. However, the stock has not fully recovered from the significant drop experienced after the VIVIAD results were announced earlier in the year, which saw 90.5% of the company's stock price wiped out.
The Alzheimer's and mild cognitive impairment market was valued at $2.2 billion across the eight major markets (US, France, Germany, Italy, Spain, UK) in 2020, according to GlobalData. While Vivoryon will no longer pursue this indication, the market was projected to grow at a compound annual growth rate of over 20% between 2020 and 2030.
