Alto Neuroscience’s depression drug trial fails at phase 2

By Helen Albert

- Last updated on GMT

© Getty Images
© Getty Images
The negative trial results have tanked the California-based biotech’s market value, with a 70% reduction in share price over the last week.

Alto Neuroscience has a focus on developing new neuropsychiatric medications. The company is using a combination of artificial intelligence (AI), brain activity and biomarker analysis to select new and better targeted potential drug candidates to advance to clinical trials.

ALTO-100 was originally developed by Neuralstem, which became Palisade Bio. It is an oral, small molecule drug that is designed to treat people with low levels of brain-derived neurotrophic factor (BDNF). It works to upregulate BDNF and promote better neurological function and neuroplasticity in the hippocampal region of the brain. It is being tested as a treatment for major depressive disorder, PTSD and bipolar-related depression.

Despite announcing​ earlier positive phase 2a results in an open label trial last year, Alto did not have the same success in its placebo controlled phase 2b trial of ALTO-100 for treatment of major depressive disorder announced​ this week.

Although the safety profile of ALTO-100 was good, the drug did not meet the primary endpoint of a positive change in the Montgomery-Åsberg Depression Rating Scale (MADRS) compared to placebo in a study including 301 participants with this type of depression. ALTO-100 also did not meet the preset secondary endpoints for the trial.

“We are disheartened by the results from this study as the unmet need in this patient population is immense. While the results are surprising and disappointing, I am proud of our team for conducting a first-of-its-kind precision biomarker-based study in psychiatry,” said Amit Etkin, founder and CEO of Alto Neuroscience.

“We will move quickly to evaluate the full data set to better understand these findings and incorporate learnings from this large data set across our platform. We remain committed to our mission of helping patients get better faster by bringing precision medicine to psychiatry, and we expect our strong cash balance to support us through multiple near-term clinical milestones across our pipeline.”

A difficult field to succeed in

Developing new and successful psychiatry drugs is notoriously difficult. Successful placebo-controlled trials in this area are few and far between, as there is often a strong placebo response combined with an increasing response to the test therapy, which can make it hard to achieve a statistically significant positive result for the drug being tested if the trial is not well designed.

However, this does not seem to be the case with the Alto trial, with reports​ suggesting the trial was well designed with a normal placebo response.

ALTO-100 is also being tested for treatment of bipolar depression and PTSD so it may yet prove successful in a different group of patients.

The company also has three other potential treatments for major depressive disorder in clinical testing –ALTO-203, ALTO-300, and ALTO-202– all of which have different mechanisms of action to ALTO-100 so it may yet be possible for it to find a new treatment for this difficult to treat condition.

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