Biomarker-driven treatment improves symptoms of major depressive disorder in phase 2 study

Key takeaways:

• ALTO-300 demonstrated clinically meaningful improvements in MDD with a favorable safety profile.
• Significantly more patients with an EEG biomarker achieved clinical response than those without.

The investigational antidepressant ALTO-300 demonstrated clinically meaningful improvements in patients with major depressive disorder, particularly among those characterized by a biomarker, according to a manufacturer press release.

“Our conviction in the promise of precision medicine for the brain is bolstered by these results,” Amit Etkin, MD, PhD, founder, president and CEO of Alto Neuroscience, said in the release. “Data from the ALTO-300 study showcase the potential of targeting patients’ underlying neurobiology to achieve clear clinical benefit and further validate our precision drug development approach.”

The 8-week, phase 2a study enrolled 239 patients aged 18 to 74 years who were treated with ALTO-300 while staying on a background antidepressant. Researchers analyzed 110 patients who underwent electroencephalography at baseline, using what they described as a “rigorous machine learning-driven data science approach” to identify a biomarker of likely drug response.

Patients characterized by the biomarker (n = 55) had a mean 8.3-point reduction in mean score on the Montgomery–Åsberg Depression Rating Scale compared with 5.7 points in the non-biomarker group, the release stated. At week 4, significantly more patients with the biomarker achieved clinical response (47%) than those without it (27%), a trend that continued through week 8 (62% vs. 47%).

Patients had no unexpected adverse events, and the treatment showed a favorable safety and tolerability profile, according to the release.

The results paved the way for a phase 2b study examining ALTO-300 in 200 patients with major depressive disorder. Results are expected in the first half of 2025.