Revamping Biosimilar Reviews to Spur Drug Development in Oncology

Biosimilar reviews confirm any differences between a potential biosimilar and its reference product, but new research shows that these reviews may need to provide more information about efficacy to encourage more drug development in oncology.

A biosimilar is a biologic drug that has been shown to be similar to an approved reference biologic product in terms of structure, biologic activity, safety, and efficiency. It is only very recent that biosimilar monoclonal antibodies (mAbs) were approved for the treatment of cancer, including trastuzumab and bevacizumab biosimilars, which gained regulatory approval in the US in July 2019. 

Oncologists may feel less comfortable with anticancer biosimilars as supportive care agents, but a recent survey uncovered no significant differences between anticancer biosimilars and more expensive biologics. 

The survey of US community oncologists featured in the Journal of Clinical Oncology found that any oncologist concerns that were observed can be in part attributed to other factors and any true difference is considered likely to fall within the equivalence margins and be of no clinical relevance.

The problem may lie with the biosimilar review process, researchers explained.

In order to be approved in the US, it must be proved that a biosimilar is “highly similar to the reference product notwithstanding minor differences in clinically inactive components and show no clinically meaningful differences between the biosimilar and the reference product in terms of safety, purity, and potency,” they wrote.

The reviews, however, do not have to use multiple study population and efficacy end points like disease-free survival (DFS), progression-free survival (PFS), or overall survival (OS), which are typically required for demonstrating clinical benefit in registration trials of novel anticancer therapeutics. 

The reviews also do not need to use short-term surrogate end points, such as overall response rate measured at a specific time point or pathologic complete response, which are both considered “adequate and more appropriate for detecting potential product-related differences in a comparative clinical study of a potential anticancer biosimilar.”

Researchers also pointed out that current regulatory guidelines do not require comparative clinical efficacy studies in all circumstances.

For example, FDA guidance states that a comparative clinical study is necessary, “if there is residual uncertainty about whether there are clinically meaningful differences between the proposed [biosimilar] product and the reference product based on structural and functional characterization, animal testing, human PK and PD data, and clinical immunogenicity assessment.”

This requirement may impede drug development of similar for cancer treatment, researchers stated.

“For many biosimilar mAbs, however, the absence of robust PD efficacy measures, as well as their importance to clinical outcome, means that comparative clinical trials will likely remain necessary,” they wrote in the study. “In our view, the requirement for such studies is also particularly likely for oncology mAbs, where biosimilars may be used with curative intent, and prescribers will want to appraise comparative clinical data.”

Researchers advised regulators and drug manufacturers to perform comparative clinical studies for oncology biosimilars. They suggested that the studies should “be performed in a sensitive population using appropriate end points to allow detection of any clinically meaningful differences between the treatments, should they exist.”

“As biosimilars become more widely available in oncology, it is important that clinicians appreciate the distinct confirmatory role of comparative clinical studies in the biosimilar paradigm,” they concluded.