Arrivo BioVentures Repurposes Depression Drug SP-624 Targeting Gender-Specific Gene Expression
Key Insights
Arrivo BioVentures (search) is focusing its depression (search) drug, SP-624, on women after initial trials showed significant efficacy in female patients but not in males, based on gene expression differences.
SP-624, a SIRT6 (search) activator, targets gene pathways preferentially important in females with depression (search), potentially offering a novel approach compared to traditional receptor-based antidepressants.
A new Phase 2b trial is underway, designed to evaluate SP-624 specifically in women, with the aim of achieving registration and changing the landscape of depression (search) drug development.
Arrivo BioVentures (search) is shifting its focus for the depression (search) drug SP-624 towards women, following unexpected results from an earlier Phase 2 trial. The company believes gender-specific gene expression could be the key to unlocking the drug's potential in treating major depressive disorder (search) (MDD).
Unexpected Trial Results Lead to New Strategy
Initial Phase 2 trials of SP-624, a sirtuin 6 (SIRT6 (search)) activator, showed promise but lacked statistical significance across the entire study population. However, a deeper analysis revealed a striking difference between male and female participants. According to Arrivo CEO Steve Butts, women responded very well to the drug, while men did not show significant improvement.
Further investigation led Arrivo to the work of Marianne Seney, a University of Pittsburgh scientist, whose research highlighted that males and females express opposite genes when depressed. This discovery aligned with SP-624's epigenetic mechanism as a gene silencer, suggesting it preferentially silences gene pathways important to females with depression (search).
Targeting SIRT6 for Gender-Specific Treatment
SP-624 targets SIRT6 (search), an enzyme involved in DNA repair, gene expression, and other cellular functions. The company's research indicates that SIRT6 silences inflammatory pathways, particularly NF-kB, and inhibits gene promoters affecting glucose homeostasis. This mechanism may explain the clinically significant results observed in women, who comprised two-thirds of the initial study population.
According to company data, 25% of female patients achieved remission by the fourth week of treatment, and 38% experienced a 50% or greater reduction in symptoms.
Phase 2b Trial Focused on Women
Arrivo has initiated a Phase 2b trial to further investigate SP-624 as a female-specific depression (search) treatment. While the trial enrolls both men and women, the primary endpoint will focus solely on the reduction of symptoms in women. The goal is to gather data that could support registration and potentially transform the approach to depression drug development.
Butts noted that past studies have indicated that women tend to respond better to selective serotonin reuptake inhibitors (SSRIs), while men may respond better to norepinephrine-based products. SP-624 could offer a new option for female patients in a market where innovation is greatly needed.
Future Potential
Arrivo anticipates a data readout from the Phase 2b study in late 2025 or early 2026. Beyond depression (search), the company is exploring SP-624's potential in age-related and neurodegenerative diseases, diabetes, and obesity. If successful, Butts believes SP-624 could signal a shift in the pharmaceutical industry towards targeting the biological basis of neuropsychiatric diseases, rather than relying on moderately effective, receptor-based products like SSRIs or SNRIs.