The antibody-drug conjugate (ADC) manufacturing landscape offers the potential to leverage significant opportunities for cancer treatment, but faces complex challenges.
Nevertheless, the ADC market potential is significant, with one estimate by CAS, a division of the American Chemical Society, sizing it to $8.6bn in 2022.
“Each ADC is unique, often containing highly cytotoxic compounds that require specialized handling,” Philip Schaefer, Head of Business Franchises, Process Solutions, Merck KGaA, told Pharmaceutical Technology.
However, an ADC’s bespoke nature adds to its complexity. “The multi-step synthesis, conjugation, and purification processes increase the risk of product loss, contamination, and higher production costs, which can delay market entry,” Schaefer says.
As a result, the majority of ADC projects are outsourced to Contract Development and Manufacturing Organizations (CDMOs), to save on costs. These CDMOs then manage the manufacturing process from concept and ideation stages through to its completion.
How ADCs works
ADCs are medicines that focus on precise delivery, targeting specific cells in the body, such as cancer cells. One 2022 research study described ADCs as the “biological missile” for targeted cancer therapy. The particular treatment type combines a monoclonal antibody (mAb), which then acts as a guide that directs a drug to target a particular area. The mAb discovers and then attaches itself to certain antigens located on the surface of targeted cells.
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The process enables the drug to be delivered directly to the targeted cell, leading to the cell’s death and minimal damage to healthy cells surrounding this target area. The idea is that employing a targeted approach like ADC can result in fewer side effects than other treatments. ADCs, therefore, provide a way to treat diseases more precisely and safely.
Navigating the ADC manufacturing process
The research and development (R&D) process for ADCs consists of several key steps. The first stage involves selecting the target area to deliver the treatment. Researchers identify tumour antigens that the ADC will target. Then comes the antibody engineering stage, which optimises the antibody for better binding and specificity. The conjugation step is next, which involves a manufacturer using a stable linker to connect a cytotoxic drug to the antibody.
After these stages are complete, in vitro and in vivo testing assess the ADC’s efficacy and safety. The ADC formulation then needs to remains stable and effective during storage and administration. If is successful, the next step is to test the ADC in clinical trials. At this point, the ADC is evaluated in humans, and then the manufacturer will explore the regulatory approval process required for commercialisation of the treatment.
“Throughout this journey, collaboration among scientists from various fields is crucial to address the complexities of developing effective ADC therapies,” says Schaefer.
Driving the demand for ADCs
“With around 800 molecules in the pipeline, ADC development is gaining substantial momentum,” Schaefer says. The rapid pace of ADC manufacturing shows no signs of slowing down either. “Successful clinical trials have significantly increased confidence in ADCs, attracting heightened interest from pharmaceutical companies and investors,” adds Schaefer.
The potential to offer patients an alternative cancer treatment to those currently available is driving demand for ADC development and seeing pharmaceutical companies launch their treatments. Earlier this year, AstraZeneca, a leader in the ADC space announced its plans to build a $1.5 billion ADC facility in Singapore by 2029. GSK is developing its own pipeline of ADCs, including a B7-H3-targeted ADC called GSK5764227, which recently received breakthrough therapy designation from the US Food and Drug Administration.
New treatments are being explored at an increasingly rapid pace, with more than 160 ADCs reported to be in development. Of these, 85% are related to ADCs that treat solid tumours, largely breast and lung cancers, the Nature Reviews article states in an April 2024 analysis.
“Unlike traditional chemotherapy, ADCs deliver highly potent cytotoxic agents directly to cancer cells, minimising damage to healthy tissue,” says Schaefer. As ADCs are designed to create a targeted approach that improves therapeutic efficacy and decreases side effects, they are recognised for their potential to provide vital support to both patients and healthcare providers.
Advancements in biotechnology, such as improved antibody engineering and conjugation techniques, are noted for their ability to enhance the specificity and stability of ADCs. “These innovations make the development process more efficient, further fueling demand in the market,” says Schaefer.
Science and business moves forward
In 2024, the ADC landscape has evolved significantly with advancements in both science and business.
“Regulatory approvals have increased, along with innovations in linker chemistry and payload design, allowing ADCs to target a broader range of cancers, including solid tumours,” Schaefer continues. Over the past decade, 13 ADCs have been approved by the FDA, with seven gaining approvals in the last five years, and several more are currently undergoing clinical trials at various stages.
The increase in ADC research reflects a shift towards personalised medicine, which strives to improve treatment outcomes and minimize side effects. “Investment is rising, driven by academia-industry collaborations, and ADCs remain a strategic priority following key deals and acquisitions in 2023 and 2024,” says Schaefer. “These trends highlight ADCs’ growing potential as effective cancer therapies,” he adds.
Evolving ADC advancements
Yet, despite this potential, the unique nature of ADC development also creates barriers to entry, namely relating to its multi-step process, safety risks and costs concerns. More R&D is taking place in an effort to overcome these ADC challenges.
“Recent innovations in the ADC space include a shift towards less toxic and less potent payloads, enhancing the safety and efficacy profiles of these therapies,” says Schaefer. Advancements in linker and conjugation technologies are also improving performance.
“We are seeing ADC applications expand into first-line treatments and broader indications, with novel conjugates being explored beyond oncology to address conditions such as atherosclerosis and inflammatory diseases,” says Schaefer. Additionally, dual-targeting approaches and enhanced payloads are gaining traction. “Real-time monitoring capabilities and regulatory flexibility further facilitate ADC development and application,” Schaefer notes.
“This evolution reflects a growing commitment to harnessing the potential of ADCs for a wider range of therapeutic applications, ultimately improving patient outcomes,” Schaefer adds.
