As the patents for blockbuster biologics expire, a new era of opportunity emerges, ushering in the rise of biosimilars. These biologic alternatives offer the promise of affordable care, broader global access, and lucrative growth for pharmaceutical companies. But the key to unlocking this promise lies in a crucial phase: biosimilar clinical trials.

Clinical trials for biosimilars are not merely regulatory hurdles; they are strategic levers that drive global expansion, ensure regulatory compliance, and establish market credibility. In this post-patent era, mastering biosimilar clinical trials is the foundation for entering new markets, boosting profitability, and achieving long-term scalability.

The Patent Cliff: Turning Expiry into Opportunity

Many high-revenue biologic drugs have entered the patent expiration phase, including agents like Humira, Herceptin, and Enbrel. These drugs once dominated their therapeutic categories, but the expiration of their patents has created a multi-billion-dollar opportunity for biosimilar developers.

With the global biologics market projected to exceed $600 billion by 2025, the biosimilar industry is poised for exponential growth. However, gaining regulatory approval and market share requires more than replication—it requires demonstrating biosimilarity through rigorous, science-driven clinical trials.

Why Clinical Trials Are Essential for Biosimilars

Unlike small-molecule generics, biosimilars are complex, large-molecule biologics produced using living cells. Therefore, proving biosimilarity involves more than structural similarity—it requires substantial evidence of comparable efficacy, safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity.

Regulatory bodies such as the FDA, EMA, PMDA, and WHO require detailed comparative data from clinical trials that assess how closely the biosimilar matches its reference product in terms of therapeutic outcomes. These trials validate not only scientific equivalence but also build confidence among healthcare providers, payers, and patients, essential for biosimilar adoption and market penetration.

How Biosimilar Trials Accelerate Market Access and Growth

Entry into Global Regulated and Semi-Regulated Markets

With a well-designed biosimilar clinical trial protocol aligned with ICH guidelines and WHO recommendations, companies can submit a unified data package across multiple regions. This harmonized approach enables faster approval in diverse regulatory jurisdictions, including the US, Europe, Asia-Pacific, and Latin America.

Such global regulatory strategies reduce redundancy, streamline timelines, and increase return on investment by allowing a single clinical trial to unlock access to multiple international markets.

Enhancing Physician and Payer Confidence

For biosimilars to gain commercial traction, they must overcome skepticism from healthcare providers and insurers. Clinical trials provide the comparative clinical evidence necessary to assure stakeholders of the biosimilar’s therapeutic equivalence.

This confidence is critical to achieving formulary inclusion, payer coverage, and widespread physician prescribing—all of which influence biosimilar commercialization.

Tapping First-Mover Advantage in Emerging Economies

Emerging markets present enormous untapped potential, especially in regions where the cost of biologics is a barrier. However, these markets often require localized clinical data to satisfy regulatory and ethical standards.

Conducting regionally focused biosimilar trials allows companies to meet local requirements and build trust with national health authorities, achieving first-mover advantage in high-demand, cost-sensitive settings.

Clinical Trials as Strategic Tools for Global Expansion

Harmonized Protocols for Multi-Country Approvals

Pharmaceutical companies are increasingly designing adaptive clinical trials that comply with harmonized international standards. These protocols facilitate cross-border submissions and minimize the need for additional studies, making global rollouts faster and more cost-efficient.

Such trial designs enable manufacturers to leverage clinical development frameworks that align with both stringent and semi-stringent regulators, expanding their global footprint efficiently.

Localized Trials for Regional Relevance

While global trial designs offer efficiency, localized biosimilar trials offer contextual relevance. Factors like ethnicity, healthcare infrastructure, and disease epidemiology can affect trial outcomes.

By customizing clinical trials to local settings, companies not only meet regulatory expectations but also gather real-world insights that enhance the biosimilar’s value proposition in targeted markets.

Attracting Strategic Partners and Licensing Deals

Robust clinical trial data also serve as powerful marketing tools. They attract global licensing partners, regional distributors, and co-development collaborators looking to enter or expand in biosimilar markets.

With a compelling clinical evidence package, companies can negotiate favorable terms for out-licensing, thereby multiplying revenue streams and accelerating global scale without extensive infrastructure investments.

Case Studies: Clinical Trials That Redefined Market Entry

Amgen: Multi-Regional Approvals through Clinical Excellence

Amgen’s biosimilar to Humira, Amgevita, leveraged extensive Phase 3 clinical trial data to secure approval in over 40 countries. By aligning its trials with FDA, EMA, and Health Canada requirements, Amgen demonstrated how a single development program can catalyze global biosimilar launch strategies.

Biocon and Mylan: Expanding Global Reach with Trastuzumab

The co-development of Ogivri (a trastuzumab biosimilar) by Biocon and Mylan exemplifies how biosimilar trials can bridge high-income and low-income markets. Their clinical data supported FDA and WHO approvals, enabling entry into both the US and emerging economies, particularly in oncology care.

Celltrion: Remsima’s Rise to Global Recognition

Celltrion’s Remsima (infliximab biosimilar) gained EU approval by demonstrating biosimilarity through rigorous trials. Its clinical success in Europe later supported approvals in the Middle East and Asia, positioning Celltrion as a leader in biosimilar market expansion.

Business Impact: The Economics of Trial Investment

While the cost of biosimilar development can range between $100 million and $300 million, the financial return can be substantial. Clinical trials are not just R&D costs—they are strategic investments that unlock revenue across product lifecycles.

Key benefits include:

• Lower development costs than novel biologics
• Quicker ROI through licensing and global commercialization
• Scalability through label expansions and new indications
• Market penetration via payer acceptance and prescribing behavior

Moreover, as biosimilar portfolios expand, companies can leverage platform-based development to reduce costs per molecule and increase pipeline velocity.

Evolving Regulatory Support for Biosimilar Trials

Global regulators have recognized the potential of biosimilars and are actively working to facilitate their development and approval.

• The FDA’s Biosimilar Action Plan (BAP) offers guidance on interchangeability and abbreviated approval pathways.
• The European Medicines Agency (EMA) has simplified clinical requirements for well-characterized biosimilars.
• The World Health Organization (WHO) is expanding its biosimilar prequalification program to increase access in low- and middle-income countries.

These shifts indicate a favorable climate for companies that invest in regulatory-aligned trial designs and pursue early engagement with health authorities.

The Future: Digitization, Personalization, and Real-World Data

Biosimilar clinical trials are evolving rapidly with the adoption of:

• AI-driven patient recruitment and protocol optimization
• Decentralized clinical trial models (DCTs) to reach diverse populations
• Real-world evidence (RWE) integration for post-market validation
• Patient-centric endpoints and digital health tools to enhance engagement

Companies that embrace these innovations will not only reduce trial costs and timelines but also differentiate their offerings in a competitive global landscape.

Clinical Trials as Catalysts of the Biosimilar Boom

In the biosimilar arena, clinical trials are more than a regulatory formality—they are the core drivers of market access, profitability, and scalability. As biologic patents expire and healthcare systems seek affordable alternatives, biosimilar developers that prioritize strategic clinical development will lead the way.

Investing in high-quality, globally relevant biosimilar clinical trials is the smartest way to open new markets, gain stakeholder trust, and build a resilient biosimilar business.

Success in the post-patent era belongs to those who understand: the trial is the strategy.

Read More: How to Plan Biosimilar Clinical Trials in India: Regulations, Process, Benefits, and Data Standards for USFDA & EMA Submissions

Biostatistics involves the application of statistical techniques for the design and analysis of clinical trial data. In addition to the conduct of trials which encompasses regulatory approval processes, informed consent, and patient monitoring, and safety, it is necessary to ensure that trials are appropriately designed to have suitable statistical power to meet the end point(s) and the correct trial design is employed to prove the hypothesis. As important as any of these is that the data gathered is analyzed and interpreted appropriately as it is used for clinical decision-making and that the data is collected in such a way that makes it reliable, valid, and accurate. Biostatistics involves processes such as the detection of patterns in data sets (descriptive statistics), statistical tests applied to data to make conclusions regarding populations (inferential statistics), and statistical modelling techniques to determine relationships between factors.

Biostatistical services form an important aspect of all steps in a clinical trial from design, data collection, analysis, interpretation and reporting, and post-marketing surveillance (PMS). The figure below shows the various steps in which biostatistics is used in clinical trials.

Trial design and development

Before the inception of a clinical trial, it is necessary to have a robust and comprehensive statistical analysis plan (SAP) in place that provides a detailed description of the various statistical tests and analysis methods that will be used to analyze the collected qualitative and quantitative data. SAPs are required to be submitted along with the study protocol prior to initiation of a clinical trial to regulatory agencies. SAPs contain the following information:

• primary and secondary end points
• details for interim analysis
• handling of missing data
• sample size calculations
• final analysis details
• significance levels
• statistical tests intended to be used
• tables and figures to be included in the analysis reports
• randomization plans, etc.
• trial design (superiority, equivalence, non-inferiority, adaptive, basket, umbrella)

Data management

Biostatistics forms an integral part of the data collection process wherein it is necessary for biostatisticians to be involved in various activities related to data management such as:

• the design of data collections instruments such as case report forms (CRFs) and electronic databases if they are used to capture patient information
• validation of instruments such as questionnaires and patient-reported outcome (PRO) instruments
• statistical methods to ensure the accuracy, completeness, and reliability if the data and conduct interim analysis if needed to help adjust the protocol.

Validity of data is critical for regulatory approval making it imperative to ensure the correctness of data entry taking care to avoid errors and inconsistencies. Biostatisticians must help design CRF and analyzable data sets as per Clinical Data Acquisition Standards Harmonization (CDASH) and Clinical Data Interchange Standards Consortium (CDISC) standards.

Statistical analysis

Often the most important role of biostatistics in clinical trials is the statistical analysis component. This involves the use of various statistical analytical techniques such as

• inferential statistics
• descriptive statistics
• multivariate and linear regression models (to draw relationships between two variables in the population)
• survival analysis (Kaplan-Meier and Cox proportional hazards model)

Data interpretation and reporting

Following analysis of datasets from sample patient groups, it is necessary for biostatisticians to be involves in the interpretation of data such that can be put into an easily readable format that can be understood and applied by clinicians and other healthcare professionals (HCPs). Cross-functional organization and communication between biostatisticians and clinical teams is necessary to help in interpretation of results and manuscript preparation activities such as the inclusion of key figures and tables to represent important findings. Submission to most regulatory agencies requires the involvement of biostatisticians to create statistical analysis reports or clinical study reports (CSR) that present the statistical data in certain formats.

Post-marketing surveillance (PMS)

Phase IV trials or PMS studies are becoming increasingly important to inform healthcare decisions from data that is gathered in the real-world. This data is often inconsistent as it is collected from disparate sources and of large volume making it essential to have a biostatistics team in place to handle this data and enable valid conclusions to be drawn from it. Biostatistics is applied in real-world evidence (RWE) analysis which involves analysis of data from real-world sources such as insurance claims, patient registries, and electronic health records (EHRs) to help identify relationships between variables. Potential safety signals can also be detected using biostatistical methods that form a part of adverse event reporting and pharmacovigilance studies. Meta-analysis, survival analysis, and risk evaluation and mitigation strategies (REMS) also involves the use of biostatistics in PMS.

Biostatistics is an integral part of all steps of clinical trials encompassing trial design to study publication. It helps ensure that the data collected is accurate and reliable and valid conclusions are drawn from the data that feed into further decision-making.

Read More:  https://prorelixresearch.com/cdisc-standards-for-biostatistics-and-clinical-data-management/

References

• Understanding Biostatistics Interpretation – StatPearls – NCBI Bookshelf (nih.gov)
• Biostatistics: A toolkit for exploration, validation and interpretation of clinical data – PMC (nih.gov)
• Guidance for biostatisticians on their essential contributions to clinical and translational research protocol review – PMC (nih.gov)

Biologicals products occupy a significant place in the treatment landscape of several autoimmune diseases and cancers and are most often the only choice of treatment and management of several diseases but are associated with and are limited in their usage because of their high costs and lower accessibility. Monoclonal antibodies, vaccines, and therapeutic proteins which are all biologicals are produced from living organisms by complex biotechnology processes and are more difficult to characterize than simple, small molecules resulting in high costs associated with their production and their complex and labile nature which requires highly controlled storage and transport systems. Thus, developing a so-called ‘generic’ version of biological products is important to help curtail medication costs and improve access to patients by increasing market competition and availability especially for illnesses where there are no alternative treatment options. 

Biosimilars are biological products that are highly similar to and have no clinically meaningful differences from an FDA-approved reference product. Based on inherent variation in the structure of biological molecules due to variability in sources and length, complex manufacturing process, it is normal for slight differences to exist between different batches of biological products and between the reference biological and biosimilars. Therefore, demonstrating ‘similarity’ between a reference product and biosimilar involves thorough characterization studies to compare characteristics such as purity, chemical activity, and bioactivity and human pharmacokinetic and pharmacodynamic studies to ensure that there is no clinically meaningful difference between the products. 

There are several advantages for the introduction of biosimilars in healthcare that offer an number of potential benefits to patients, payers, and providers (depicted in the figure below): 

Cost savings

Following the expiration of reference biological patents, introduction of biosimilars in the market increases competition and broadens the availability of treatment options thereby driving down the price of biologicals which further increases patient accessibility to treatments and reduces the burden on the healthcare system. Additionally, biosimilars also cost less than reference biologicals as their manufacturing costs are lower and time for development is shorter which adds to their lower price benefits.

Improved outcomes

Certain diseases can only be treated with biological products, in such instances, accessibility to biosimilars can help manage these diseases effectively as well as help in the treatment of other diseases where biologicals may be more efficacious than chemically synthesized drugs. Biosimilars also lower costs of biological treatments facilitating patient adherence to the treatments which consequently leads to better outcomes.

Increased treatment options

Biosimilars provide a broader and more affordable range of treatment options for both patients and healthcare systems allowing for improved access. In some cases, biosimilars may have a superior treatment profile than the reference biologicals in terms of formulation characteristics which is also beneficial for patients.

Healthcare system savings/sustainability

The cost savings that are realized using biosimilars can be allocated for the management of other diseases/conditions relieving the healthcare system of its financial burden by providing treatments for a wide range of diseases. 

Market competition

Improved innovation and a focus of research and development (R&D) activities by biopharmaceutical companies occur due to the introduction of biosimilars in the market fostering innovation and improvements in clinical outcomes. Market competition also forces manufacturers to decrease the cost of otherwise expensive biological products leading to a lower economic burden and increased affordability from a patient and payer perspective. 

Broader patient access

The lower cost of biosimilars increases their use by a wider population of patients of a lower socioeconomic demographic.

The above advantages of biosimilars are reasons for their increased importance and adoption in the healthcare system serving all stakeholders involved. Despite these benefits, concerns with toxicity and immunogenicity of biosimilars continue to remain important and must be carefully evaluated by healthcare providers prior to their prescription and well as regulatory authorities before their introduction into the market. Increased number of clinical trials in a larger number of patients and integration of real-world data from the use of biosimilars will help generate more data to support their applicability and increase their use.

Read More : Biosimilar clinical trials and study designs’ considerations

References

• Biological Product Definitions (fda.gov)
• Benefits, Concerns, and Future Directions of Biosimilars in Inflammatory Bowel Disease – PMC (nih.gov)
• Advantages and efficacy of biosimilar drugs | Gouvernement du Québec (quebec.ca)
• Prescriber Perspectives on Biosimilar Adoption and Potential Role of Clinical Pharmacology: A Workshop Summary – PMC (nih.gov)