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Disappointing Phase 2b Results for ALTO-100 for MDD, Precision Medicine
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Although safety and tolerability was positive, ALTO-100 failed to reach primary endpoint in MDD study.
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BREAKING NEWS
Disappointing news comes as a result of a phase 2b study (NCT05712187) of ALTO-100 as a treatment for major depressive disorder, according to Alto Neurosciences.1 The company noted the agent failed to meet the primary endpoint, which was a change in Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline as compared with placebo.
The clinical study was a randomized, double-blind, placebo-controlled trial that included 301 adults with MDD in 34 clinical trial sites across the United States. The study looked at the agent in patients with MDD who had objective cognitive biomarker, which was assessed prior to randomization, and represents a novel approach.
Topline results indicated that ALTO-100 had a favorable safety profile. The most common treatment related adverse events included headache, nausea, and abnormal dreams, which were similarly experienced by participants in the placebo group. These safety and tolerability data were similar to previous findings of ALTO-100. However, the agent did not produce statistically significant improvement in depression symptoms as measured by the MADRS when compared with placebo.
Amit Etkin, MD, PhD, founder and chief executive officer of Alto Neuroscience, shared that the company was “disheartened” by the results of the study. “I am proud of our team for conducting a first-of-its-kind precision biomarker-based study in psychiatry,” Etkin said in a press release.1 “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.”
ALTO-100 is part of the company’s Precision Psychiatry Platform, which aims to use brain biomarkers to predict treatment response. “The predictive biomarker identified, and prospectively replicated, for ALTO-100 is a test of verbal memory, or the ability to recall lists of unrelated words. Verbal memory is a direct measure of hippocampal neuroplasticity; therefore, selecting patients based on poor performance on this test provides a clear biological link between the proposed pro-plasticity mechanism of ALTO-100 and this characteristic of responsive patients," the website explains. "The test used to compute the biomarker score is Alto’s digital adaptation of a well validated instrument that has been used in clinical practice for assessing memory for more than 80 years and is highly test-retest reliable. The web-based memory test is self-administered and can be completed by the patient in less than 20 minutes in any setting, including at home. This convenient, reliable, and efficient test enables high-quality data collection at a broad clinical scale.”2
Alto’s chief medical officer, Adam Savitz, MD, PhD, also shared his disappointment. “While the Phase 2b results did not replicate the clinical results observed in the Phase 2a trial, we believe our approach to collecting and stratifying based on biomarkers represents an innovative approach to developing neurIopsychiatric drugs,” he said in a press statement.1
The company plans on further investigating the data to determine the next steps for ALTO-100. In the meantime, there is a phase 2b study of the agent for use in bipolar depression and they have other agents (ALTO-203 and ALTO-300) being studied for MDD.1
For more information on ALTO-100 and other advances in psychiatry, subscribe to Psychiatric Times.
References
1. Alto Neuroscience Reports Topline Results from a Phase 2b Trial Evaluating ALTO-100 as a Treatment for Major Depressive Disorder. Business Wire. Press release. October 22, 2024. Accessed October 23, 2024. https://www.businesswire.com/news/home/20241022197716/en/Alto-Neuroscience-Reports-Topline-Results-from-a-Phase-2b-Trial-Evaluating-ALTO-100-as-a-Treatment-for-Major-Depressive-Disorder
2. Alto Neuroscience Announces Enrollment Completion in Phase 2b Study of ALTO-100 in Major Depressive Disorder. Alto Neurosciences. July 16, 2024. Accessed October 23, 2024. https://investors.altoneuroscience.com/news/news-details/2024/Alto-Neuroscience-Announces-Enrollment-Completion-in-Phase-2b-Study-of-ALTO-100-in-Major-Depressive-Disorder/default.aspx
