Establishing Equivalence Margins for a Ph3 Biosimilar Trial in Rheumatoid Arthritis: From Choice of Endpoints to Regulatory Experience

• Activity Number: 659
• Type: Contributed
• Date/Time: Thursday, August 13, 2015 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Steven Y. Hua* and Kerry Barker
• Companies: Pfizer Research and Development and Pfizer Inc.
• Keywords: Biosimilar ; equivalence margin ; Rheumatoid Arthritis ; meta analysis ; type-I error rate ; equivalence

Abstract

The two best known and most commonly used summation measures for activity of Rheumatoid Arthritis (RA) are DAS-28 (a measurement of disease activity) and ACR20 (measures change over time in such activity). DAS-28 is viewed as a quantitative measure while ACR20 is considered a responder variable (yes or no). Biosimilars are structurally highly similar versions of marketed biologics that are supported by appropriate analytical testing and clinical trials to demonstrate that they are sufficiently "similar" to their reference innovator biologics. In this talk, we present choice of margins for the difference in ACR20 response rates derived from a meta-analysis of several historical trials. We also present a side-by-side comparison between ACR20 and DAS-28 to demonstrate different characteristics of the two endpoints including sample size, power, metric (difference vs. ratio), margins size and available historic data. A discussion that highlights some regulatory opinions on the sizes of equivalence margin and confidence interval to demonstrate efficacy equivalence is also provided. Lastly, we give some thoughts on practical values and seeking a unified approach for equivalence margins.