Monoclonal Antibody Clinical Research Trends: Key Insights and Gaps
Monoclonal antibodies (mAbs) have transformed therapeutic approaches for cancers, immune disorders, and infectious diseases. Their high specificity and success rates in clinical trials have driven increasing investment in their development. The World Health Organization examined clinical trial trends over the 2014–2023 period, emphasizing geographical distribution, disease focus, and gaps in research that could inform future R&D priorities.
Growth of Monoclonal Antibody Clinical Research
The past decade has seen substantial growth in mAb clinical trials. The number of registered interventional trials increased from 1,207 in the 2004–2013 period to 2,066 in the 2014–2023 period. The peak in 2021 was driven in part by COVID-19-related research, followed by a decline in 2022 and 2023, which may reflect reduced pandemic-related studies and delays in registering new trials
A significant trend observed was the rise of early-phase trials, including phase 0 trials introduced in 2020 and an increased number of phase 1 trials. The diversification of mAb targets has also contributed to this expansion. In 2021, 25% of new therapeutic mAbs entering clinical trials were directed at previously untargeted antigens, marking a shift from traditional targets.
Most trials focused on noncommunicable diseases (NCDs), with malignant neoplasms and immune disorders accounting for 84% of trials. NCDs, also known as chronic diseases, tend to be of long duration and are the result of a combination of genetic, physiological, environmental and behavioural factors. The primary types of NCDs include cardiovascular diseases (like heart attacks and strokes), cancers, chronic respiratory diseases (such as chronic obstructive pulmonary disease and asthma), and diabetes. NCDs disproportionately impact individuals in low- and middle-income countries, where nearly 75% of global NCD-related deaths (around 32 million) occur.
In contrast, only 11% of trials targeted communicable diseases, indicating an ongoing imbalance despite increasing interest in mAbs for infectious disease applications.
Geographical Disparities in Clinical Trials
Despite an increase in clinical trials in low- and middle-income countries (LMICs), high-income countries (HICs) remain the dominant sites for mAb research. Between 2014 and 2023, 66% of all mAb clinical trials were conducted in at least one HIC, while only 1% were conducted in low-income countries (LICs).
Most trials were concentrated in North America, Europe, and, more recently, China. The Western Pacific region, particularly China, has become a key player in mAb research, reflecting the country’s growing emphasis on advanced therapies and regulatory improvements.
In contrast, Africa remains underrepresented in mAb clinical research, with most trials in the region focusing on immune and infectious diseases rather than cancer treatment. Despite the rising burden of cancer in Africa, research and funding remain limited. Between 2009 and 2020, African researchers published five times more studies on infectious diseases than on cancer. Limited local research infrastructure and funding, combined with regulatory hurdles, contribute to this gap.
The lack of clear regulatory pathways in many LMICs further exacerbates the disparity. Complex and prolonged approval processes discourage clinical trial investments, hindering the development and distribution of mAb-based therapies in these regions. Addressing these barriers requires harmonized regulatory frameworks and incentives to support local research initiatives.
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Gaps in Pediatric and Adolescent Clinical Trials
Most mAb clinical trials over the past decade have been conducted in adults, with minimal representation of pediatric and adolescent populations. Only 4% of trials included children aged 0–9 years, and 6% included adolescents aged 10–17 years. This underrepresentation raises concerns about the availability of age-appropriate safety and efficacy data.
Monoclonal antibodies have demonstrated potential in pediatric medicine, particularly in treating immune disorders and infectious diseases. Recent studies on mAbs for respiratory syncytial virus (RSV), malaria, and HIV have underscored their utility in addressing major global child health concerns. However, progress remains slow, particularly in pediatric oncology, where many promising mAb candidates fail to advance past early-phase trials.
Regulatory challenges contribute to the lack of pediatric trials. Stringent safety requirements, ethical concerns, and limited financial incentives for developing pediatric formulations discourage research in this area. Expanding pediatric mAb trials would provide critical data to ensure that these therapies are safe and effective for all age groups.
Disease Focus: Dominance of Noncommunicable Diseases
Noncommunicable diseases accounted for 84% of mAb clinical trials during the 2014–2023 period, with malignant neoplasms representing over half of these studies. The top therapeutic areas included lymphomas, multiple myeloma, breast cancer, lung cancer, and inflammatory dermatoses.
Checkpoint inhibitors and other immune-modulating mAbs have significantly impacted cancer treatment, improving outcomes for various malignancies. In immune disorders, mAbs targeting cytokines and immune checkpoints continue to drive therapeutic innovation.
Despite the success of mAbs in treating NCDs, their use in communicable diseases remains limited. Only 11% of trials targeted infectious diseases, with respiratory infections (44%) and HIV (12%) being the primary focus. The COVID-19 pandemic accelerated research in this area, with 61 trials registered for COVID-19 alone. Other notable infectious disease targets included RSV (16 trials), malaria (10 trials), and hepatitis B (8 trials).
The need for effective therapies against emerging infectious diseases highlights the potential for mAbs in outbreak response. Expanding research in this field could improve preparedness for future pandemics and address persistent gaps in treatment options for high-burden infections.
Future Directions and Research Priorities
Expanding Clinical Research in LMICs
Diversifying Disease Targets
Integrating Access Strategies into R&D Plans
As monoclonal antibodies continue to shape modern medicine, addressing these research gaps and disparities will be critical to ensuring that their benefits are widely distributed. Strategic investments in clinical trials, regulatory improvements, and global access initiatives will help unlock the full potential of mAbs for diverse patient populations worldwide.
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