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Alto Neuroscience's ALTO-100 Fails to Meet Primary Endpoint in Phase 2b Depression Trial

• Alto Neuroscience's ALTO-100, designed to upregulate BDNF, did not meet the primary endpoint in a Phase 2b trial for major depressive disorder. • The trial, involving 301 participants, assessed the change in Montgomery-Åsberg Depression Rating Scale (MADRS) compared to placebo, but ALTO-100 showed no significant improvement. • Despite the disappointing results, Alto Neuroscience will analyze the data and continue developing other depression treatments like ALTO-203, ALTO-300 and ALTO-202. • ALTO-100 is still being tested for bipolar depression and PTSD, offering potential for success in different patient populations.

Alto Neuroscience's ALTO-100, an oral small molecule drug designed to treat individuals with low levels of brain-derived neurotrophic factor (BDNF), failed to meet its primary endpoint in a Phase 2b clinical trial for major depressive disorder (MDD). The study, involving 301 participants, assessed the efficacy of ALTO-100 in improving depression symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) compared to placebo.

Trial Results

Despite demonstrating a good safety profile, ALTO-100 did not show a statistically significant improvement in MADRS scores compared to placebo. The drug also failed to meet the pre-specified secondary endpoints of the trial. This outcome contrasts with earlier positive Phase 2a results from an open-label trial.
"We are disheartened by the results from this study as the unmet need in this patient population is immense," said Amit Etkin, founder and CEO of Alto Neuroscience. "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."

ALTO-100 Mechanism and Previous Research

ALTO-100, originally developed by Neuralstem (later Palisade Bio), aims to upregulate BDNF and promote neurological function and neuroplasticity in the hippocampus. The rationale behind ALTO-100 is that by increasing BDNF levels, it can alleviate symptoms of depression. The drug is also under investigation for the treatment of PTSD and bipolar-related depression.

Challenges in Psychiatric Drug Development

Developing effective psychiatric drugs is notably challenging due to factors such as a high placebo response rate and variability in patient responses. However, reports suggest that the Alto trial was well-designed with a normal placebo response, indicating that other factors contributed to the trial's failure.

Future Directions for Alto Neuroscience

Alto Neuroscience remains committed to its mission of bringing precision medicine to psychiatry. The company plans to thoroughly evaluate the data from the ALTO-100 trial to inform future research and development efforts. Alto Neuroscience has three other potential treatments for major depressive disorder in clinical testing – ALTO-203, ALTO-300, and ALTO-202 – each with different mechanisms of action. The company believes its strong cash balance will support multiple near-term clinical milestones across its pipeline.
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Reference News

[1]
Alto Neuroscience's depression drug trial fails at phase 2 - biopharma-reporter.com
biopharma-reporter.com · Oct 24, 2024

Alto Neuroscience's ALTO-100, designed to treat low BDNF levels, failed to meet primary and secondary endpoints in a pha...

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