Alto Neuroscience’s Phase 2 Trial for Depression Medication Concludes Unsuccessfully
Alto Neuroscience is dedicated to the advancement of innovative neuropsychiatric treatments. The firm harnesses artificial intelligence (AI), brain activity assessments, and biomarker analyses to identify promising drug candidates, streamlining their path to clinical trials.
The drug ALTO-100 was initially created by Neuralstem, which transitioned into Palisade Bio. This oral small molecule medication targets individuals exhibiting low levels of brain-derived neurotrophic factor (BDNF). Its mechanism focuses on increasing BDNF levels, thus enhancing neurological function and promoting neuroplasticity specifically in the hippocampus. ALTO-100 is currently undergoing trials for major depressive disorder, PTSD, and depression associated with bipolar disorder.
While the company had previously reported favourable phase 2a trial results last year in an open-label setting, they faced setbacks in their placebo-controlled phase 2b trial aimed at treating major depressive disorder, as revealed this week. Despite the drug showing a good safety profile, it failed to achieve the primary endpoint, which involved observing a significant change in the Montgomery-Åsberg Depression Rating Scale (MADRS) when compared to placebo, in a study comprising 301 participants suffering from this disorder. ALTO-100 also did not fulfill its predetermined secondary objectives for the trial.
Amit Etkin, the founder and CEO of Alto Neuroscience, expressed disappointment over the study’s outcome, noting, “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.”
He further added, “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 challenging domain for success
The development of new psychiatric drugs is infamously challenging. Successful placebo-controlled trials in this field are rare due to the substantial placebo effect often observed, combined with the rising responsiveness to the experimental treatment, complicating the attainment of statistically significant positive outcomes unless trials are meticulously designed.
Nevertheless, the Alto trial appears to have been properly structured, with reports indicating normal placebo responses. ALTO-100 is also under consideration for treating bipolar depression and PTSD, indicating potential success with alternative patient groups.
Additionally, the company has three other drug candidates for major depressive disorder currently in clinical evaluation—ALTO-203, ALTO-300, and ALTO-202—all presenting different mechanisms of action from ALTO-100, suggesting possibilities for identifying new solutions for this challenging-to-treat condition.