Following the approval in 1986 of Orthoclone OKT3, the first therapeutic monoclonal antibody product, a class of new protein-based therapeutic drugs was introduced and became the dominant product class within the biopharmaceutical market.
Today, several monoclonal antibodies have been approved for the treatment of a variety of diseases, ranging from those that target orphan disease indications with a small patient population, to those that target much larger patient populations and demographics, such as for oncology, asthma, and rheumatoid arthritis.

In Issue 8 of The Altascientist, we explore the role of anti-drug antibodies (ADAs) in therapeutic development, their impact on efficacy, and detection strategies, including:

• Challenges encountered in ADA assays
• Cell-based or non-cell-based assays to measure neutralization
• How Altasciences can help

The Challenges of Anti-Drug Antibody Challenges Assays in Bioanalysis

Matrix interference in immunogenicity assays, especially when handling disease-type populations, is one of the most challenging parameters to resolve. Multiple factors can contribute to interference, such as the disease population and demographic, the drug itself, the rheumatoid factor (RF), the presence of a soluble target or receptor, an endogenous counterpart, a co-administered drug, pre-existing antibodies, and other proteins such as lipid or hemoglobin.

Another challenge is the limited access to oncology donors who appropriately represent the target population, often complicating the determination of the pre-study cut-point in immunogenicity oncology studies. The cut-point analysis must be assessed using the targeted population of the clinical study with a sufficient number of sample donors that are essential to yield a suitable statistical analysis for cut-point determination. 

Ideally, the use of the specific disease population is preferable if a sufficient amount of donors adequately representing the clinical study are available. However, this is often not possible, and the challenge is even greater when the clinical study targets different disease types.

How Altasciences’ Expertise Can Overcome Bioanalytical Anti-Drug Antibody Challenges

As more therapeutic proteins are being developed, Altasciences’ technology and bioanalytical methods are evolving to achieve highly sensitive and robust ADA assays. This allows our team to detect positive ADA samples and characterize the immunogenicity risks associated with each therapeutic drug to ensure a better patient safety profile. Several strategies have been used at Altasciences to mitigate matrix interferences observed in disease populations, making it easier to assess immunogenicity in complex clinical studies aimed at targeting various populations.

Although some specialists may prefer to be more conservative and develop bioanalytical methods that are highly sensitive, at Altasciences, we stress the importance of putting into context the clinical relevance of the study to ensure that results generated in the ADA assay are not overestimated and misleading.

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Biologics have become the fastest-growing class of therapeutic compounds, with seven of the top-10 selling drugs in 2023 being biologics, each exceeding sales of $10 billion USD.  In 2022, biosimilars accounted for 13.7% of all spending on biologics, compared with the 8.9% in 2021.

Biologics have provided treatment options for people who suffer from some of the most serious medical conditions, such as cancer and genetic disorders.

A biosimilar is a copy of a biologic medicine that is similar, but not identical, to the original medicine. It enters the market subsequent to the patent expiration of a previously authorized version of a biologic. A biosimilar is approved only after showing that it is “highly similar” to an approved biological product, known as the reference product, in terms of structure, purity, potency, safety, pharmacokinetics, and in many cases, efficacy, with allowable minor differences.

In Issue 4 of The Altascientist, learn about the growing interest of biosimilars, and key considerations in pharmacokinetic (PK) studies, as well as:

• The rise of the biosimilar market
• The regulatory landscape
• How Altasciences puts biosimilars to the test
• Altasciences’ expertise in bioanalysis  
• Key considerations for biosimilar clinical pharmacology studies
• Ensuring the continued success of biosimilar programs

Considerations and Study Challenges for Biosimilars

Early awareness of study challenges is crucial in running a successful early-phase biosimilar development program, and certain considerations must be taken into account before beginning a study.

Recruitment is often one the most challenging aspects of the biosimilar clinical trial process and can lead to trial delays if not managed effectively. The inclusion and exclusion criteria for healthy participants in a biosimilar bioequivalence study are often much stricter than a standard bioequivalence study on a small molecule.

Additionally, as a biosimilar product is not exactly the same as the reference product, there are also increased safety risks associated with the administration of the test product. Key safety considerations include immunogenicity, hypersensitivity reactions, and an increased risk for other adverse effects.

How Altasciences  Can Support Your Biosimilar Drug Development

Bioanalytical considerations are another important factor. Unlike small molecule drugs, biologics exhibit a significant level of complexity which is driven by the fact that their production is dependent on a living system, such as a microorganism, a plant, or animal cells.

Altasciences supports method development, GCP/GLP-compliant biosimilar assay development validation, and sample analysis for PK and immunogenicity/anti-drug antibody (ADA) testing, and we are proud of our bioanalytical expertise with LC-MS/MS and ligand binding platforms . We provide support for all stages of drug development (discovery to preclinical to Phase IV) for both small and large molecules programs.

“Altasciences has the perfect mix of innovator and generic drug development experience, with a thorough understanding of the regulatory complexities involved in biosimilar clinical pharmacology studies. Companies developing biosimilars are collaborating with us because of our firsthand experience, distinctive recruitment strategies, and speed in conducting biosimilar clinical trials that require a customized approach based on the therapeutic indication and study-specific goals. Our expertise allows us to accelerate our clients’ biosimilar development programs so they can offer greater treatment options and more cost-effective medications to patients in need.”–Danielle Salha Senior Director, Global Immunology, Ligand Binding Assays

Explore all issues of The Altascientist in our Resource Center. And don’t forget to subscribe to “The Altascientist: Audiobooks” on Spotify, Apple Podcasts, or wherever you get your audio content.