The notoriously tricky indication of Alzheimer’s disease has defeated another candidate, with Vivoryon Therapeutics’ lead asset missing all endpoints in a phase 2 trial and sending the company’s stock plunging 90%.
The European phase 2b study, dubbed VIVIAD, involved 259 patients with mild cognitive impairment and mild Alzheimer's receiving either a 600 mg twice daily dose of the glutaminyl cyclase inhibitor varoglutamstat or placebo. The primary endpoint was change over time on working memory and attention, with secondary endpoints assessing other measures of cognitive function and ability to perform everyday tasks.
The drug didn’t show “a statistically significant difference in change over time on cognition” or hit any of the other endpoints, Vivoryon said in a pre-market release Monday.
The 600 mg dose did at least seem to maintain the safety stats seen in preliminary readouts, with varoglutamstat “generally well tolerated” and producing similar rates of serious and severe treatment-emergent adverse events to placebo along with low discontinuation rates caused by adverse events. There was also no evidence of symptomatic amyloid-related imaging abnormalities (ARIA), a side effect that has haunted amyloid-lowering monoclonal antibody treatments for Alzheimer’s.
Still, it’s tough news for Vivoryon, which as recently as December was anticipating “potential discussions with the FDA” in the wake of the VIVIAD readout. A phase 2 study in the U.S., called VIVA-MIND, is ongoing.
For now, the biotech is conducting an “in-depth analysis of the results, including analyses of additional pre-specified exploratory endpoints …. and distinct patient cohorts as defined in the statistical analysis plan, including ApoE4 status, tau level, dose level and pre-treatment.”
“We are profoundly disappointed by the outcome of the VIVIAD phase 2b study of varoglutamstat in the early AD patient population given the huge unmet need for new safe and effective oral therapies,” Vivoryon CEO Frank Weber, M.D., said in this morning’s release.
“While these results are not what we had hoped for, VIVIAD is a comprehensive, diligently designed and high-quality study and we are doing all we can to fully analyze the dataset as quickly as possible to gain insights into key findings that might influence varoglutamstat clinical development and help advance the science and understanding of this devastating disease,” Weber added.
Investors didn’t appear reassured, sending Vivoryon’s shares crashing 90% to 76 euro cents when the Stuttgart stock exchange opened this morning from a Friday closing price of 8.36 euros.
The strong market reaction is likely because varoglutamstat is Vivoryon’s only clinical-stage asset. Last year, the biotech began the process of identifying oral QPTC/L inhibitors that could have potential as second-generation compounds to treat early-stage Alzheimer's.
In a Monday morning note, Jefferies analysts said that despite the additional analyses, “given primary and secondary endpoints were all missed, it is difficult to see a path forward for varoglutamstat.”
“We note the trial's baseline demographics are reported to be highly representative of an early AD patient population, as planned, suggesting the failure was not down to recruitment of the 'wrong' patients, as has previously been a problem for AD trials,” the analysts added.