By Kimberly Salgado, ICON plc
Advancements in biologic therapies have greatly improved our ability to treat cancer over the last few decades — but are typically very costly. With patent expirations encompassing numerous notable oncology biologics, opportunities for oncology biosimilar development are abundant. Biosimilars, less expensive treatments made to closely emulate biologics with expired patents, play a critical role in making treatment more accessible to cancer patients due to their affordability compared to the name brand product (originator). And, with typically lower development costs and shorter timelines to obtain marketing authorisation, biosimilars present an attractive prospect to sponsors as well.
There are many challenges, however, that set oncology biosimilar development apart from that of novel biologics. For sponsors interested in entering this space, it will be critical for them to be prepared for challenges such as developing complex modalities equivalent to the marketed product, overcoming inconsistent global regulatory requirements and hurdles, selecting and recruiting trial patients when the marketed product is already available and encouraging biosimilar adoption by patients, providers and insurance company formularies.
Developing complex modalities
Over the next fifteen years, the prevalent oncology treatments with expiring patents will become increasingly complex — and developing corresponding biosimilars will become more difficult. The relevant modalities for the coming years fall into a few main categories, each with unique development hurdles: monoclonal antibodies (mAbs); next-generation antibody therapies (including antibody-drug conjugates [ADCs] and bispecific antibodies [BsAbs]); and cell therapies such as CAR T.
Monoclonal antibodies (mAbs) for oncology treatment have been under development for greater than 10 years, with the first biosimilar version of rituximab approved by EMA in 2017. Since that time, multiple other biosimilar mAbs for oncology indications have been approved or are under development. Many additional mAbs, which target specific antigens to more precisely bind to cancer cells, are reaching the end of their patent life, and hence more biosimilar mAbs will make their way to the market. Chief concerns for biosimilar mAb development and manufacture involve the potential for variability, as well as sensitivity to changes in the manufacturing process. For these reasons, continued analytical assessments will be paramount to ensuring quality. The clinical trial pathway traditionally consisted of conducting both a pharmacokinetic sub-study (PKSS) and a comparative clinical trial (CCS) to prove the biosimilar’s equivalence to the marketed product. These human trials assess the safety, efficacy, pharmacokinetic and immunologic profiles of the biosimilar under development compared to the already approved and marketed originator. Recently, the FDA (2024) and EMA (2025) released draft guidelines and a reflection paper, respectively, regarding the necessity of conducing the larger CCS trials traditionally been mandated by regulatory agencies. The future development pathway of mAb’s may indeed be abbreviated; however, conducting the smaller PKSS trial in oncology patients still comes with many challenges.
Next-generation antibody therapies, including antibody drug conjugates (ADCs) and bispecific antibodies (BsAbs,) will make up the next wave of biosimilars. The process of creating an ADC by linking a cytotoxic drug to an mAb is highly complex. This means that these drugs will need to meet extremely specific characterisation requirements to ensure sufficient similarity to the reference product — for example, the drug/antibody ratio and site of attachment.
Meanwhile, BsAbs call for a stable, high-quality cell line due to their elevated risk of abnormal folding. Additionally, their increased likelihood of immune reaction means they will require particularly rigorous pharmacokinetic/pharmacodynamic and immunogenicity studies.
Finally, cell therapies will begin to enter eligibility for biosimilar development, particularly CAR T therapies. Currently, it is unclear whether cell therapy biosimilars will be acceptable to regulatory bodies, since cell therapies are primarily autologous and therefore, inherently unique. There may be potential to prove similarity of the T-cell modification vector, but doing so will require extremely rigorous immunogenicity studies and characterisation analysis.
Finding the right patients
As oncology biosimilars enter clinical trials, defining the most appropriate patient cohort presents a critical design challenge. While biosimilar pharmacokinetic studies typically involve healthy volunteers, this approach may not be appropriate for oncology drugs. For example, target-mediated drug disposition — the binding of a drug to its target site — may differ significantly between healthy individuals and cancer patients. If comparability to the reference product cannot be sufficiently established in healthy subjects, randomised trials demonstrating tumour response in oncology patients may be required. Additionally, the safety profile of some antibody therapies may render them unsuitable for healthy subjects. Hence the recruitment of healthy volunteers versus oncology patients for an oncology biosimilar clinical trial must be made on a case-by-case basis.
Recruiting patients for oncology biosimilar trials can also be difficult. If the reference product is approved and accessible, cancer patients may not be willing to participate in the biosimilar clinical trials. In addition to the lack of understanding of a biosimilar by both patients and medical providers, certain oncology indications can progress quickly, making the screening process and hence a delay in treatment to ensure clinical trial eligibility off putting. Additionally, patients may find the required blood sampling and study visits burdensome, leading to trial enrolment challenges. As a result, biosimilar clinical trial recruitment may see greater success in regions where the reference biologic is difficult to access, for example due to a lack of reimbursement or regulatory approval.
Encouraging biosimilar adoption
A significant obstacle in the adoption of biosimilars is patient and provider education. Typically, providers are key influencers of patient therapeutic use, making it important to help physicians feel comfortable with biosimilars. While most physicians are aware of biosimilars, since this class of drug has now been available for some time, many hold misconceptions. For instance, some have concerns that the shorter approval process for biosimilars means that they are inferior in quality or effectiveness.
To encourage oncology biosimilar uptake, sponsors should focus on addressing hesitations and filling knowledge gaps. One method is by conducting outreach and education on biosimilars, such as through training sessions or classes for oncologists. Another approach is to proactively address common questions or concerns about a biosimilar by making information about its safety, efficacy and cost — compared to the reference product — easily accessible in a central information hub. Furthermore, it is important to collect robust post-market monitoring data that can provide evidence to support a biosimilar. With this wealth of information, physicians are likely to feel more confident prescribing biosimilars to their patients.
Preparing for the future
The oncology biosimilars landscape is expected to evolve in many ways over the coming years, offering new and exciting opportunities in the process. By anticipating likely challenges and learning how best to prepare for them, sponsors can give their products the best chance at success in this promising and important field.
To explore the oncology biosimilar development landscape and how it is likely to evolve, including further trends and considerations for oncology biosimilar modalities, regulatory requirements and post-market concerns, read ICON’s whitepaper, The future of oncology biosimilars: Considerations for development through 2040.
About the author
Kimberly Salgado, Head of Biosimilar Centre for Drug Development, ICON plc
Sponsored content by ICON plc
Filed Under: Sponsored Content
