Race and ethnicity are important considerations during drug development, with differential effects in drug exposure, efficacy, and safety across racial groups observed for some drugs. Gyawali and Ando (1) suggest that the recommended dose of 200 mg once daily for sonidegib may not be appropriate for Asian patients living in the United States. We acknowledge the importance of identifying a dose in diverse populations, and note that most patients enrolled into the major efficacy trial were White (90%), which is reflective of the prevalence of skin cancer in the United States (2). In-depth exploration of the potential effect of race on the exposure, safety, and efficacy to sonidegib was limited due to small sample sizes and a relatively nondiverse patient population.

The potential impact of race on dose is highlighted by different recommended doses for the same product approved by different regulatory agencies (3). Other factors, such as diet and body size, may also contribute to differences in dose, which may be incorrectly attributed to race. In some cases, population-specific prescribing recommendations are provided in U.S. product labeling based on multivariate population pharmacokinetic analyses and pharmacogenomic data (4). FDA supports the investigation of efficacy, safety, and pharmacokinetics in various specific populations, including race, age, and organ function.

A cross-study comparison suggests that exposure to sonidegib is higher in healthy Japanese subjects in Japan compared with healthy Western subjects (Whites and Blacks) after a single 200 mg dose of sonidegib. It is not known whether this higher exposure would be observed for Americans of Asian descent. On the basis of the small sample size, factors contributing to the potentially higher exposure in Japanese subjects relative to White subjects are not known. The clinical development program as reviewed by FDA did not include other Asian races. Therefore, data were inadequate to support alternative doses for Asian patients in the FDA-approved product labeling.

We acknowledge that racial and ethnic differences in exposure may impact the safety and effectiveness of a drug, often through effects on drug metabolism and pharmacokinetics. In addition to the challenges of including underrepresented racial populations in clinical trials, the sonidegib development program limited further evaluation of the efficacy and safety in specific populations. FDA encourage efforts to enroll diverse populations in clinical trials designed to support marketing applications so that potential differences may be evaluated in these populations. Adequate information supporting extrapolation of clinical data to the U.S. population is necessary to support statements included in product labeling.

See the original Letter to the Editor, p. 5993

No potential conflicts of interest were disclosed.

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