Topline Phase 2 Data Support Efficacy, Tolerability, and Favorable Safety of Treatment for PTSD

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A phase 2a study of a treatment for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) found evidence of efficacy, tolerability, and favorable safety in its PTSD cohort.

The study—an ongoing, first-of-its-kind, 8-week, open-label, holdout dataset-controlled clinical trial in phase 2—aimed to find biologically based data for defining predictors and correlates of the effects of the drug, ALTO-100, in individuals with MDD and/or PTSD between the ages of 18 and 69 years.^1,2

In the study, investigators measured improvements in symptoms of PTSD in a subgroup of 90 participants with primary PTSD using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), a 20-item structured interview for diagnosing and assessing PTSD symptoms that is considered the “gold standard” in PTSD assessment. The primary endpoint was a change in CAPS-5 score from baseline to week 4, with a replication threshold pre-specified as a Cohen’s d effect of 0.25 or higher in those with and without the cognitive biomarker profile.¹

In assessing the study’s topline results for the PTSD cohort (n=44), investigators noted a 17.5-point mean reduction in CAPS-5 scores compared to 12.9 points in the patient group without the biomarker profile (n=40) at week 4, which was the primary outcome timepoint (p=0.04, d=0.37).¹

They also found that approximately 46% of the participants with the biomarker achieved clinical response—or a CAPS-5 PTSD symptom reduction of 50% or more from baseline—compared to 26% of participants without the biomarker (p=0.065). The investigators identified no additional safety signals.¹

“Positive data from the PTSD cohort of our ALTO-100 study, following favorable results in MDD, represents further validation of our platform,” said Amit Etkin, MD, PhD, founder and chief executive officer of ALTO-100 developer Alto Neuroscience, in a press release.

“This result in PTSD, leveraging the same biomarker as discovered in MDD, strengthens confidence in Alto’s approach and the replicability of our data. PTSD is highly heterogeneous and notoriously difficult to treat, and these results suggest the potential to meaningfully de-risk future development in additional indications following the anticipated MDD readout in 2024. These data move us closer to transforming neuropsychiatric treatment through a robust understanding of biological drivers of treatment response at the level of individual patients.”

Alto Neuroscience announced the results of the 133-participant MDD cohort from this study in January 2023, noting that the study’s participants with moderate to severe MDD experienced significant improvement in Montgomery–Åsberg Depression Rating Scale (MADRS) scores following treatment with ALTO-100. Upon announcing these results, the company also stated that it would initiate a large phase 2b trial in participants with biomarker-defined MDD in January 2023. Topline data from the phase 2b trial for MDD are expected to be reported in the first quarter of 2024.³

Stay up-to-date on news related to research on promising new treatments for PTSD, MDD, and a wide variety of psychiatric disorders at psychiatrictimes.com.

References

1. Alto Neuroscience announces positive results from phase 2 study of ALTO-100 in post-traumatic stress disorder. Alto Neuroscience. News release. September 26, 2023. Accessed September 26, 2023. https://www.altoneuroscience.com/press-releases/positive-results-phase-2-alto-100-ptsd

2. ALTO-100 in MDD and/or PTSD. ClinicalTrials.gov. Accessed September 26, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05117632

3. Alto Neuroscience announces positive results for ALTO-100 in phase 2 study supporting advancement of first-in-class mechanism for treating depression. Alto Neuroscience. News release. January 10, 2023. Accessed September 26, 2023. https://www.altoneuroscience.com/press-releases/alto-neuroscience-announces-positive-results-for-alto-100-in-phase-2-study-supporting-advancement-of-first-in-class-mechanism-for-treating-depression