Breakthrough Clinical Results
Alto Neuroscience received FDA Fast Track designation for ALTO-101 for treating cognitive impairment associated with schizophrenia (CIAS). ALTO-101, a novel PDE4 inhibitor, has shown pro-cognitive effects in healthy volunteers. The designation aims to expedite the development and review of drugs for serious conditions with unmet medical needs. A Phase 2 proof-of-concept study of ALTO-101 in CIAS patients is ongoing. There are currently no approved treatments for CIAS, a core feature of schizophrenia impacting daily functioning and quality of life.
Key Highlights
- ALTO-101 receives FDA Fast Track designation for CIAS treatment.
- ALTO-101 is a novel PDE4 inhibitor with pro-cognitive effects.
- Fast Track designation facilitates development and review of drugs for serious conditions.
- Phase 2 proof-of-concept study of ALTO-101 in CIAS patients is ongoing.
Incidence and Prevalence
Latest Global Estimates of Schizophrenia Incidence and Prevalence
Global Prevalence
According to the most recent Global Burden of Disease study data from 2019, the global prevalence of schizophrenia stands at 23.60 million cases (95% uncertainty interval: 20.23-27.15). This represents a substantial 65% increase from 1990, when prevalence was estimated at 14.2 million cases.
Four countries—China, India, the USA, and Indonesia—account for more than half (50.72%) of the total global prevalence.
While raw numbers have increased significantly over the past three decades, age-standardized estimates have remained relatively stable globally. The global prevalence has increased only slightly from 1990 to 2019, with an annual percentage change of just 0.03% (95% confidence interval 0.01-0.05).
The global age-standardized point prevalence of schizophrenia in 2016 was estimated to be 0.28% (95% uncertainty interval: 0.24-0.31), while the mean lifetime prevalence is reported to be just below 1%. A meta-analysis found the lifetime prevalence worldwide to be 0.48% with an interquartile range of 0.34% to 0.85%.
More recent research suggests potentially higher rates, with a 2025 study indicating lifetime prevalence of 1.8% (95% CI=1.3%-2.5%) and past-year prevalence of 1.2% (95% CI=0.9%-1.8%), which are two to four times higher than previously reported.
Global Incidence
The global incidence of schizophrenia has increased from 941,000 new cases in 1990 to 1.3 million new cases in 2019, representing a 37% increase. Regional studies show varying patterns, with a 2024 study in Ningbo, China reporting an annual average reported incidence of 9.76/100,000 from 2018 to 2022.
Another 2024 study from Shandong, China found that the overall incidence decreased from 9.61 per 100,000 in 2016 to 4.40 per 100,000 in 2020.
Demographic Patterns
The male/female ratio of schizophrenia burden has remained stable at approximately 1.1 over the past 30 years, though this ratio decreases from younger to older age groups. Raw prevalence in females becomes higher than males after age 65, with males having earlier age of onset and females having longer life expectancy.
Prevalence is highest among individuals 30-59 years old compared to younger or older groups, regardless of sociodemographic index.
Regional Variations
The burden of disease is heavier in relatively less affluent regions. In countries with high socio-demographic index (SDI), both prevalence and DALYs increased, while in those with low SDI, the age-standardized incidence decreased and DALYs remained stable.
Regions with intermediate sociodemographic index accounted for a greater proportion of prevalence increase than regions with high index.
Schizophrenia contributes 13.4 million years (95% UI: 9.9-16.7) of life lived with disability to the global burden of disease.
Emerging Unmet Needs
Key Unmet Needs and Target Populations for Schizophrenia Treatment
Unmet Treatment Needs
Recent research (2021-2024) highlights several critical unmet needs in schizophrenia treatment. Cognitive function remains a significant challenge, with cognitive domains including processing speed, attention/vigilance, verbal and visual learning, and reasoning showing varied treatment responses. Social cognition has limited comparative data between treatments, indicating a substantial gap.
Negative symptoms are particularly difficult to treat with conventional antipsychotics yet significantly impact quality of life. Despite guidelines advising against it, antipsychotic polypharmacy and high-dose antipsychotic therapy continue to be used in up to 25% of cases with limited evidence for efficacy.
Language impairments in schizophrenia, including reduced verbal output and fluency, represent an emerging focus area. Long-term outcomes including social participation, morbidity, and mortality remain poorly understood, indicating a need for dedicated studies.
Underserved Populations
Treatment-resistant patients constitute approximately 20-30% of people with schizophrenia who do not respond to antipsychotics, representing a critical population needing alternative options. Research suggests treatment-resistant schizophrenia may be a distinct condition from treatment-respondent schizophrenia.
Young patients (aged 30-39) may benefit more from NMDAR-enhancing agents, with significant positive effects observed in this demographic. Patients with specific genetic factors like BDNF gene Val66Met polymorphisms may require personalized approaches, as the Met/Met genotype is associated with worse outcomes.
Research has identified several other specific subgroups requiring targeted interventions: children and adolescents, first-episode patients, patients with predominant negative symptoms, those with comorbid substance use, and older patients.
Emerging Treatment Approaches
Novel non-invasive brain stimulation techniques like Magnetic seizure therapy (MST), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) are being investigated, though evidence remains limited and results mixed.
NMDA receptor antagonists as adjunctive therapy show promise for improving cognitive function, while N-acetyl cysteine (NAC) has demonstrated significant effects specifically on working memory. Positive psychology interventions have shown promise, particularly for Chinese patients, with long-term and mid-term treatments outperforming short-term approaches.
Novel pharmacological treatments targeting muscarinic receptors, TAAR1 agonists, serotonergic pathways, and glutamate modulation have emerged as promising alternatives to traditional antipsychotics.
Psychoeducation and addressing stigma represent critical areas warranting attention, as side effects, lack of information, and negative beliefs were identified as significant barriers to treatment adherence across both oral and long-acting injectable (LAI) formulations.
Other Drugs Being Trialled for the Same Indication Using the Same MoA as ALTO-101
After reviewing the available information, I cannot provide details about drugs being trialled for the same indication using the same mechanism of action (MoA) as ALTO-101, as there is insufficient information about ALTO-101 itself.
The information indicates that there are OGA (O-GlcNAc hydrolase) inhibitors in clinical trials for Alzheimer's disease (AD) and related tauopathies. According to a 2021 publication, "Only three other OGA inhibitors have advanced into clinical trials thus far."
These OGA inhibitors function by reducing abnormal tau hyperphosphorylation and aggregation in Alzheimer's disease. Their mechanism is based on the ability of O-GlcNAcylation to compete with tau phosphorylation.
Preclinical validation has confirmed the efficacy of OGA inhibitors in different transgenic tau mice models. OGA is described as "a highly ubiquitous enzyme with many client proteins" with data confirming "a promising benign profile for OGA inhibition in healthy volunteers."
The existence of OGA PET tracers will be critical for proper dose selection for future Phase II studies.
However, without specific information about ALTO-101, including its indication and mechanism of action, I cannot determine which of these OGA inhibitors might share the same indication and MoA as ALTO-101, nor can I provide details about the intervention models used in their clinical trials.