The development of new, safe, and effective drugs for diseases such as cancer, infectious diseases, and autoimmune disorders is a multi-billion-dollar industry worldwide. Since their initial approval in the 1980s, antibody therapeutics have emerged as the predominant class of new drugs for treating these diseases and improving patient outcomes.
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Introduction
Antibody therapeutics are ideal candidates for treating these difficult-to-treat diseases as they are highly specific and consequently, new antibody therapeutics have less side-effects than traditional, non-specific therapeutic drugs. The rapid and dramatic evolution in antibody engineering since the 1980s has made this possible. The global market for these drugs is projected to be worth $300 bn by 2025.1
However, the commercialization process for this class of drugs is highly complex. Like all new drugs entering the market, antibody therapeutics undergo a long and expensive development process from discovery and preclinical development, through clinical trials and regulatory approval, to manufacturing, scale-up, market launch, and post-market monitoring. This article will explore this complex but important process.
Monoclonal Antibodies versus Polyclonal Antibodies
Discovery and Preclinical Development
This stage of the commercialization process is the first step toward developing a new antibody therapy for a disease such as cancer or autoimmune conditions. This starts with target identification. Specific biological targets such as cancer markers and viral proteins, which antibodies work on to fight disease, are identified before they enter the preclinical trial phase.
Preclinical trials are an essential part of the drug discovery and development process. Before a new antibody therapy is approved for clinical trials on humans, it must go through a series of laboratory studies on animal models and other models to ensure it is safe. Additionally, this stage assesses the drug’s biological activity.2
Preclinical development of an antibody therapeutic, like all drugs, involves several methods and studies such as in vivo and in vitro assays. Data on toxicity, dosage, pharmacokinetics, and potential side-effects are generated during these studies, which inform more complex clinical trials on humans.
Antibody therapies are a unique class of drugs due to high specificity and affinity for a binding partner, requiring specific antibody engineering methods during the drug discovery and preclinical stages.
Several methods are used in antibody engineering to create high-affinity and specific antibodies such as monoclonal and bi-specific antibody therapies. These include homology modeling, protein-protein docking, in vitro affinity maturation, 3dMAbDesign, recombinant DNA technologies to tailor antibody properties, and protein interface prediction.3
Trends in the early-stage clinical development of antibody therapeutics
Clinical Trials and Regulatory Approval
Clinical trials involve testing new drugs and therapies on various human cohorts to evaluate their efficaciousness, safety, side-effects, proper dosage, and obtain data which is used for regulatory approval. Antibody therapeutics go through the same clinical trial stages as all other drugs.
Phase I trials involve testing in healthy volunteers or small patient groups to evaluate safety and proper dosage. Phase II trials test the drug on larger patient populations side-effects and efficacy. Phase III trials are large-scale trials. This final trial confirms the drug’s efficacy, monitors side effects, and compares a new drug with existing treatments on the market. This can be a long, complex, and expensive process.
The regulatory process is vital to ensure that new drugs such as antibody therapeutics are safe for patients and can effectively treat the diseases they are designed to combat. The regulatory approval process was not designed for speed, although the COVID-19 pandemic demonstrated that regulatory approval can be sped up given the right resources.
Agencies such as the FDA and EMA are involved in the regulatory process and there are some specific applications new drug sponsors need to file for regulatory approval. The Investigational New Drug (IND) Application, for instance, is filed during the preclinical stage, and is used by the FDA to ensure that the drug will be safe for humans in clinical trials.4
The regulatory process can take a long time, potentially over a decade before a new drug is released to the market. As antibody therapeutics are an emerging class of drug, the regulatory process is especially important and presents several challenges for pharma companies and organizations developing them for the treatment of diseases.
Manufacturing and Scale-Up
Once the trial process is complete and regulatory approval has been granted, an antibody therapeutic can enter the manufacturing stage ready to be commercially launched. There are some unique challenges associated with the manufacturing and scaling-up of this class of drugs that mark their differences to other types of drugs on the market.
Firstly, bioreactors and cell cultures are necessary to produce antibodies at scale. This can be an expensive and complex procedure. Secondly, rigorous testing is vital for quality control and ensuring consistent purity and efficacy. Moreover, cost-effective, reliable supply chains are needed for large-scale distribution.
Biologics and Biosimilars: A New Frontier in Therapeutics
Market Launch and Post-Market Monitoring
These are the final commercialization steps. To successfully launch a new pharmaceutical product such as an antibody therapeutic, there must be strategies in place to ensure patient access, proper pricing, and in the case of markets such as the US, insurance coverage.
Post-marketing surveillance is equally important as a new or emerging drug such as an antibody therapeutic must be monitored to ensure its long-term safety and efficacy. This is essential and is often required by regulatory bodies. Some problems and side-effects may not have been found in the clinical trial process, necessitating constant long-term monitoring.
Patient and physician education on new therapeutics, especially ones which have been designed to treat underserved medical conditions or may be an emerging class of therapeutics, is essential as it impacts the safe and efficacious use of a drug such as an antibody therapeutic.
Challenges and Future Outlook
As can be seen above, the commercialization process for antibody therapeutics is long, complex, and can be fraught with challenges at every stage, from target identification through post-market surveillance.
Some specific challenges for this emerging class of therapies are high R&D costs, regulatory hurdles due to their status as new and emerging therapies, and competitive market pressures.
Additionally, if the therapy is being developed to fight a condition such as an autoimmune disease that only affects a small patient population, finance and sponsorship may be difficult as it may not be seen as financially viable.
Despite the challenges of commercializing these therapeutic drugs, there are some key trends that are shaping the future of their development. These include personalized antibody therapies and personalized medicine, biosimilars (drugs that contain active substances from a biological source) and antibody-drug conjugates, which deliver cancer-killing therapies without damaging normal, healthy cells.5
In summary, antibody therapeutics are an emerging, powerful, and highly specific class of drugs that are seeing intense research focus currently for their ability to target cancers, autoimmune diseases, and other debilitating conditions safer and more effectively than conventional therapies. They represent one of the most exciting frontiers in medical science now.
References
- Lu, R-M et al. (2020) Development of therapeutic antibodies for the treatment of disease Journal of Biomedical Science 27, article no.: 1 [online] BMC. Available at: https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0592-z (Accessed on 09 November 2024)
- Young, M (2024) Understanding the New Drug Application Process: A Comprehensive Guide [online] Lindus Health. Available at: https://www.lindushealth.com/blog/understanding-the-new-drug-application-process-a-comprehensive-guide (Accessed on 09 November 2024)
- Creative Biolabs (2018) Common Engineering Techniques and Strategies in Antibody Discovery [online] Available at: https://www.creative-biolabs.com/blog/index.php/engineering-techniques-antibody-discovery/ (Accessed on 09 November 2024)
- Federal Drug Administration (2022) Development and Approval Process [online] Available at: https://www.fda.gov/drugs/development-approval-process-drugs (Accessed on 09 November 2024)
- Shastry, M, PhD et al. (2023) Rise of antibody-Drug Conjugates: The Present and Future [online] ASCO. Available at: https://ascopubs.org/doi/10.1200/EDBK_390094 (Accessed on 09 November 2024)
Further Reading
A New Understanding of Viral Infection