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Soo Park, MD
Soo Park, MD
Posted: Monday, December 1, 2025
Sonidegib, a novel Hedgehog pathway inhibitor used in the treatment of locally advanced basal cell carcinoma, has demonstrated significant efficacy in clinical trials. However, the spectrum of adverse events and associated risks of the drug in real-world settings has been inadequately explored. In an effort to more clearly define the real-world safety profile of sonidegib, Chinese investigators conducted a comprehensive study using data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Their findings, which were published in Frontiers in Oncology, have the potential to enhance decision-making and optimize patient safety.
Study Details
The authors extracted FAERS reports from the third quarter of 2015 through the fourth quarter of 2024 in which sonidegib was designated as the primary drug. After the data were processed via deduplication and standardization of terminology, 1,087 individual case reports were included encompassing 2,496 adverse events. The median patient age was 73 years, and most of the reports (67.9%) originated in the United States.
Four disproportionality analysis methods—Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Multi-Item Gamma Poisson Shrinker—were used to identify statistically significant safety signals associated with sonidegib. A positive signal for an adverse event was defined as meeting the threshold criteria of any one of the disproportionality analysis methods. Time-to-onset analyses were performed on 598 reports, and sensitivity analyses were conducted to minimize confounding and to evaluate the strength of the results.
Key Results
The findings reaffirmed several toxicities well known from clinical trials of the agent, including muscle spasms, myalgia, alopecia, fatigue, nausea, vomiting, and decreased appetite. The analysis also revealed several unexpected adverse events, including pneumonia, sepsis, urinary tract infection, renal failure, hyperkalemia, atrial fibrillation, and falls. Approximately 24.4% of the adverse events occurred within the first month of receipt of sonidegib, with a median time to onset of 88 days. However, this pattern differed from clinical trial data—in studies of the drug, many adverse events tended to occur after several months of treatment. According to the authors, this disparity may be due to limitations of the FAERS data, including underreporting, missing clinical details, and potential confounding by baseline patient factors.
Conclusions
The authors concluded that while sonidegib’s core toxicity profile aligns with expectations for Hedgehog pathway inhibition, the emergence of infection-related and renal or metabolic events underscores the importance of continuous monitoring in patients receiving the drug, particularly during the early stages of treatment. They emphasized that the real-world evidence presented in this analysis supports continued vigilance to guide the safe and effective use of sonidegib in clinical practice, although the findings represent statistical associations rather than proven causation.
“These findings provide real-world insights into the safety profile of sonidegib, thereby supporting its safe and rational use by clinicians. However, given the inherent limitations of FAERS, including reporting bias, incomplete clinical information, and potential confounding by concomitant medications, these results should be interpreted as statistical signals rather than evidence of causation. Further prospective studies are warranted to validate these observations,” they stated.
Disclosure: For full disclosures of all study authors, visit frontiersin.org.
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