Association Between Efficacy and Pharmacokinetics of DMB-3115 and its Originator Ustekinumab in Patients with Chronic Plaque Psoriasis: An Exposure-Response Analysis.

INTRODUCTION: DMB-3115 is a biosimilar to ustekinumab (Stelara®). Although a single-dose study conducted in Europe showed that the pharmacokinetics of DMB-3115 was equivalent to that of ustekinumab, another single-dose study in Japan suggested that the maximum serum concentration (Cmax) of DMB-3115 might be slightly lower than that of ustekinumab in the Japanese population. Thus, we conducted a post hoc analysis of randomized controlled studies. METHODS: The single-dose DMB-3115-1 and DMB-3115-3 studies enrolled healthy participants. The DMB-3115-2 study enrolled patients with moderate-to-severe chronic plaque psoriasis. It comprised 2 periods (Weeks 0-28 and 28-52), and we used the data through Week 12, during which patients received the assigned treatments at Weeks 0 and 4. Across all studies, participants were randomized to receive subcutaneous DMB-3115 or Stelara. We conducted regression analysis to investigate the relationships between the Cmax and efficacy outcomes using the data of participants receiving DMB-3115 or Stelara in the DMB-3115-2 study. We also conducted population pharmacokinetic (PK) analysis using the data of participants receiving DMB-3115 in the DMB-3115-1, -2, and -3 studies. Based on its results, we simulated the Cmax in the Japanese population. RESULTS: In the regression analysis, the combined Cmax of DMB-3115 and ustekinumab was not statistically associated with the percent change in Psoriasis Area and Severity Index (PASI) score from baseline to Week 12 or PASI-75 achievement (at least 75% improvement from baseline) at Week 12. Additionally, the gradual slopes of the regression line and curve suggested that the difference in Cmax is not expected to have a meaningful impact on clinical efficacy. In the population PK analysis, the simulated maximum concentrations in the Japanese population were within the range of those observed in the DMB-3115-2 study. CONCLUSION: The difference in Cmax of DMB-3115 is not expected to have a meaningful impact on its efficacy.