A new systematic review shows that analytical and functional clinical trials provide sufficient evidence to demonstrate the safety and efficacy of biosimilars. Based on the results of the review, testing requirements for monoclonal antibody biosimilars could be reduced without reducing the quality of the studies.1
“We analyzed (Marketing Authorization Applications) reviews of biosimilars (monoclonal antibodies) and fusion proteins by the (European Medicines Agency’s Committee for Medicinal Products for Human Use) and found that in the majority of cases (29/36 cases) the quality was good/ CMC packaging was matched to successful clinical trials leading to (marketing authorization),” the researchers wrote.
Biosimilars can treat complex diseases such as cancer, but they can be expensive, and the high costs contribute to uneven distribution of biosimilars across countries. Biologics account for 35% of Europe’s pharmaceuticals by list price and have grown at a CAGR of 11.3% over the past five years.2 Biosimilar competition (i.e., multiple suppliers of the same substance) is critical to reducing health care costs.1
Products with lower sales value are attractive to biosimilar manufacturers due to clinical development costs. The cost of developing biosimilars ranges from $100 to $300 million, while the cost of developing small molecules ranges from $1 to $5 million. The cost difference is attributed to trial length.
The study, led by Nadine Kirsch-Stefan and Elena Guillen from the Paul Ehrlich Institute in Langen, Germany, provides evidence to support a more flexible approach to data requirements for approval of complex biosimilars. The researchers specifically examined the role of quality/chemistry, manufacturing, and controls (CMC) and clinical data in the biosimilar marketing authorization decision-making process. The team found that shortening the trial time didn’t change anything, making everything more cost-effective. Conclusions of a study.
The requirements for biosimilar trials vary depending on the drug being developed, but studies typically include pharmacokinetic studies, efficacy and safety studies, and immunogenicity studies. These trials are designed to provide sufficient evidence to show that the biosimilar is highly similar to the reference product and has clinically meaningful differences in safety and effectiveness.
The researchers looked at conclusions drawn after data were submitted to regulators as part of a biosimilar marketing authorization application, as well as 4-6 months of safety and immunogenicity data, and the full data set submitted during the evaluation period a year later . The researchers found that sending data to institutions within 4-6 months compared with 12 months did not affect the study’s conclusions.
“The conclusions drawn after the initial submission of the data had not in any case changed after the study was completed 12 months later, suggesting that such a long trial was not necessary,” the researchers wrote.
The researchers noted that clinical trials often provide incomplete or insufficient data and that biosimilars may have different safety and efficacy profiles compared to reference products.
“For the three biosimilar candidates analyzed, the (pharmacokinetic) studies were deemed insufficient, which led to the conduct of a new, acceptable (pharmacokinetic) trial,” the researchers wrote. “Reasons for repeating (pharmacokinetic) trials are due to methodological issues and differences in formulation buffers, or because of the representativeness of the test product used.”
The study found that 22% of the trials had no manufacturing or quality issues but raised concerns about clinical data. In the event of formal failure of efficacy trials, biosimilarity is accepted by regulatory agencies due to analytical/functional comparability and similar pharmacokinetic profiles. Overall, this study highlights the importance of chemistry, manufacturing, and controls in the biosimilar marketing authorization decision-making process, suggesting that improving the quality and completeness of clinical data can streamline the biosimilar approval process.
“We conclude that a sufficiently robust analytical/functional similarity package, coupled with (pharmacokinetic) trials capturing safety and immunogenicity data, is sufficient for biosimilar (monoclonal antibody) testing,” the researchers wrote. ) and fusion protein regulatory decisions.” “In some cases, if deemed necessary… shorter efficacy trials that end at or near the time point of the primary efficacy analysis can provide additional safety and immunogenicity information.”
refer to
- Kirsch-Stefan, N., Guillen, E., Ekman, N., et al. Are the results of clinical efficacy trials important for regulatory decisions about biosimilars? Biopharmaceuticals 37, 855–871 (2023). https://doi.org/10.1007/s40259-023-00631-4
- IQVIA. White paper: Impact of biosimilar competition in Europe in 2022. December 2022. https://www.iqvia.com/library/white-papers/the-impact-of-biosimilar-competition-in-europe-2022. Accessed: April 30, 2023.