Phase 2 study initiated to assess ALTO-203 in major depressive disorder

Key takeaways:

• The phase 2 study of ALTO-203 will involve about 60 adults with MDD and evidence of anhedonia.
• ALTO-203 has demonstrated an ability to increase positive emotion compared with placebo in a prior phase 1 study.

Alto Neuroscience Inc. has initiated a phase 2 study to determine the safety, tolerability and pharmacokinetics of ALTO-203 among patients with major depressive disorder and to evaluate its effectiveness as an antidepressant.

According to a company press release, ALTO-203 is a novel, small-molecule histamine H3 receptor inverse agonist. In a phase 1 study, various dose levels of ALTO-203 demonstrated an acute increase in positive emotion compared with placebo.

In this phase 2, double-blind, single- and multiple-dose study, approximately 60 adult patients with major depressive disorder (MDD) and evidence of anhedonia will be studied over two distinct periods.

Acute change in positive emotion will serve as the first period’s primary outcome. Researchers will assess this outcome using the alertness and mood components of the Bond-Lader Visual Analog Scale, which was previously used in a phase 1 study of ALTO-203.

Researchers also will assess safety of ALTO-203 in a second period of the study that will use a 28-day, multidose exposure design.

Topline data from the study can be expected in the first half of 2025, the release stated.

“This is the fifth phase 2 study we have initiated across our pipeline, a milestone that marks significant progress in our efforts to redefine mental healthcare through our Precision Psychiatry Platform,” Jessica Powell, Alto’s chief development officer, said in the release. “We look forward to completing this proof-of-concept study in patients, as we believe this response may be an important attribute of an antidepressant to benefit patients with MDD and higher levels of anhedonia specifically.”