Vivoryon Therapeutics announced that varoglutamstat, its lead asset for treating Alzheimer’s—an inhibitor (an active compound that obstructs or neutralizes its biological target) of the enzyme glutaminyl cyclase (a carbamoyl phosphatase that catalyzes the combination of glutamine)—did not meet its endpoint in the phase 2 trial. This led to the share price dropping 90 percent, a nuclear bomb for a company of that size. Which will make it more challenging for the company to get financial support from big pharma or therapeutics companies.
The European phase 2b study VIVIAD randomized 259 participants with Mild Cognitive Impairment and mild Alzheimer’s disease to receive 600 mg twice daily or placebo. The primary endpoint was a change in working memory and attention, with secondary endpoints of additional cognitive measures and perform-based measures of activities of daily living.
But there comes a devastating defeat for every anticipated victory: Varoglutamstat failed to show a statistically significant difference in cognitive function and reach any secondary endpoints. Vivoryon said in a pre-market press release that it was ‘unable to meet endpoints.’
However, the safety profile of varoglutamstat aligns with what was reported earlier, as no signs of symptomatic ARIA were observed. The lack of efficacy, on the other hand, came as a significant blow to Vivoryon. “We are profoundly disappointed by the outcome of the VIVIAD phase 2b study of varoglutamstat in the early AD patient population,” said Vivoryon CEO Frank Weber in a press statement. ‘A new safe and effective oral therapy’ for Alzheimer’s disease is overdue.
Vivoryon states that, in response to the trial results, an in-depth analysis of these data is now being completed by looking at secondary and exploratory endpoints and different patient subgroups to obtain sub-group information that may guide future clinical development efforts. Analysts, however, remain pessimistic. They point to the primary analysis and the secondary and exploratory assessments not meeting the prespecified criteria for success. They highlight that failing to meet its endpoint is not a good sign, placing the likelihood that varoglutamstat could become an effective therapy at less than 20 percent.
The market’s response was equally swift and brutal: Vivoryon’s share price dropped to 76 cents from an earlier closing price of 8.36 euros. Because vivoglutamstat is Vivoryon’s only clinical-stage asset, the magnitude of the drop highlights the need for this program to pan out.
The road ahead for Vivoryon remains challenging, as it remains difficult to regain investor confidence and develop any path forward for the Alzheimer’s program. While the companies continue to believe in the potential of their drugs, the science of Alzheimer’s disease remains frustratingly difficult to understand and treat.
Source: James Waldron, Fierce Biotech, fiercebiotech.com March 4, 2024
