Data Mining and Bioinformatics Analysis of a Novel Adverse Event Signal of Fezolinetant: A Real-World Analysis of the US FDA Adverse Event Reporting System Database
Author(s)
Swarnendu Sahoo, PharmD, PhD1, Eswaran Maheswari, Sr., PhD2.
1Student, M S Ramaiah University of Applied Sciences, Bangalore, India, 2Pharmacy Practice, M S Ramaiah University of Applied Sciences, Bangalore, India.
1Student, M S Ramaiah University of Applied Sciences, Bangalore, India, 2Pharmacy Practice, M S Ramaiah University of Applied Sciences, Bangalore, India.
OBJECTIVES: To identify novel ADR signals for Fezolinetant using the FAERS database and validate the leading signal through molecular docking.
METHODS: FAERS data was analyzed using disproportionality analysis, focusing on reports where fezolinetant was the primary suspect, with standardized MedDRA queries (SMQs). Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) were calculated using OpenVigil. The signals were considered positive if PRR ≥ 2, Chi-square > 4, and ROR -1.96SE > 2. The genes associated with the signal were retrieved from OMIM, Gene Cards, Huge Navigator and NCBI database. Fezolinetant targets predicted by an online ligand-based target prediction tool (probability > 0) were intersected with dysarthria genes in a Venn Diagram analysis and visualised in STRING v11.5. Signal validation was performed using molecular docking studies using the Schrödinger Maestro interface, which evaluated the binding interactions between the ligand and target protein.
RESULTS: Dysarthria, not previously associated with fezolinetant, emerged as a novel signal. The FAERS database had 30,668,520 adverse events reported and 1,111 were associated with Fezolinetant since its approval in 2023. OpenVigil data revealed five reports for dysarthria. PRR was 3.77, ROR 3.79 and Chi-Square 7.61 indicating a positive signal. Implicated genes in dysarthria included GRM1, SLC6A1, MME, DRD3, and PDE10A, with binding affinities of -8.43, -7.42, -6.16, -5.44, and -4.98 kcal/mol, respectively.
CONCLUSIONS: The strong gene-binding affinities of fezolinetant suggest a potential link to dysarthria, warranting further pharmacoepidemiologic validation. These insights may support post-marketing surveillance and help clinicians monitor for dysarthria among patients administered with fezolinetant.
Key Words: Fezolinetant, Dysarthria, Signal-Detection, Adverse Drug Reactions, Molecular docking
METHODS: FAERS data was analyzed using disproportionality analysis, focusing on reports where fezolinetant was the primary suspect, with standardized MedDRA queries (SMQs). Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) were calculated using OpenVigil. The signals were considered positive if PRR ≥ 2, Chi-square > 4, and ROR -1.96SE > 2. The genes associated with the signal were retrieved from OMIM, Gene Cards, Huge Navigator and NCBI database. Fezolinetant targets predicted by an online ligand-based target prediction tool (probability > 0) were intersected with dysarthria genes in a Venn Diagram analysis and visualised in STRING v11.5. Signal validation was performed using molecular docking studies using the Schrödinger Maestro interface, which evaluated the binding interactions between the ligand and target protein.
RESULTS: Dysarthria, not previously associated with fezolinetant, emerged as a novel signal. The FAERS database had 30,668,520 adverse events reported and 1,111 were associated with Fezolinetant since its approval in 2023. OpenVigil data revealed five reports for dysarthria. PRR was 3.77, ROR 3.79 and Chi-Square 7.61 indicating a positive signal. Implicated genes in dysarthria included GRM1, SLC6A1, MME, DRD3, and PDE10A, with binding affinities of -8.43, -7.42, -6.16, -5.44, and -4.98 kcal/mol, respectively.
CONCLUSIONS: The strong gene-binding affinities of fezolinetant suggest a potential link to dysarthria, warranting further pharmacoepidemiologic validation. These insights may support post-marketing surveillance and help clinicians monitor for dysarthria among patients administered with fezolinetant.
Key Words: Fezolinetant, Dysarthria, Signal-Detection, Adverse Drug Reactions, Molecular docking
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
RWD51
Topic
Epidemiology & Public Health, Real World Data & Information Systems, Study Approaches
Topic Subcategory
Distributed Data & Research Networks
Disease
Neurological Disorders