Tracking the Antibody-Drug Conjugates Market Boom

Insights into the fast-evolving Antibody-Drug Conjugates Market

Antibody-drug conjugates (ADCs) represent a promising advancement in targeted cancer therapy, utilizing monoclonal antibodies (mAbs) to precisely deliver powerful cytotoxic agents to cancer cells. Their ability to enhance treatment effectiveness while minimizing systemic toxicity has made them a focal point in oncology, both in research and clinical applications. The global antibody drug conjugates market size was $4.00 billion in 2021 and is predicted to reach $13.13 billion by 2030, representing a CAGR of 14.12% during the forecast period 2021-2030.

ADC Design

An antibody-drug conjugate (ADC) is composed of three key elements: a monoclonal antibody (mAb) produced in vitro, a linker, and a cytotoxic payload. The mAb specifically binds to a cancer cell antigen, the linker facilitates the attachment of the mAb to the cytotoxic payload, and the payload is responsible for selectively destroying cancer cells.

“The technological advancements in developing ADCs are building our confidence in their potential to become the backbone of cancer care. We have limitless possibilities in exploring ADCs as a monotherapy and in combinations with other cancer medicines with potential to bring benefit to a broad population of cancer patients”

Puja Sapra

Senior Vice President, Biologics Engineering & Oncology Targeted Discovery, AstraZeneca

Mechanism of ADC Action

The key antitumor mechanism of antibody-drug conjugates (ADCs) involves delivering the cytotoxic payload directly to tumor cells. Upon binding of the monoclonal antibody (mAb) to the target antigen, the ADC is internalized by the tumor cell. The subsequent breakdown of the linker facilitates intracellular release of the payload, enabling its microtubule- or DNA-damaging effects. Additionally, the process of antibody binding and internalization may be further optimized through pharmacologic modifications or enhancements.

ADC Pipeline

ADCs are among the fastest-growing approaches in anticancer therapy. Over 370 new ADCs have been introduced into clinical trials, leading to 11 FDA approvals so far. The clinical success of ADCs in treating both solid and hematologic malignancies has driven remarkable growth in the field. Numerous ADCs are now undergoing phase III trials, either as monotherapy or in combination treatments, while a growing number of novel ADCs are advancing through the early stages of drug development.

List of FDA Approved ADCs

Recent Developments

• A planned interim analysis of the DESTINY-Breast09 phase 3 trial revealed positive topline results, indicating that ENHERTU®, when combined with pertuzumab, achieved a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to taxane, trastuzumab, and pertuzumab (THP) as a first-line treatment for patients with HER2-positive metastatic breast cancer. ENHERTU is a specifically engineered HER2-directed DXd antibody-drug conjugate (ADC), originally discovered by Daiichi Sankyo. It is being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.
• On January 8, 2024, Johnson & Johnson revealed its plan to acquire Ambrx Biopharma for $2 billion. Ambrx Biopharma was initially established around a technology designed to produce proteins with non-canonical amino acids at specific sites. The integration of these amino acids into the antibody component of antibody-drug conjugates (ADCs) allows for site-specific, uniform, and stable conjugation of the cytotoxic payload, which is anticipated to enhance the therapeutic index.
• In 2024, Genmab completed a significant acquisition of ProfoundBio for $1.8 billion, securing three antibody-drug conjugates (ADCs) in clinical development. Two of these ADCs feature a proprietary hydrophilic linker designed to mask the hydrophobicity of the topoisomerase 1 inhibitor exatecan. This approach facilitates a high drug–antibody ratio (DAR) and ensures efficient payload delivery while preserving favorable physicochemical and pharmacokinetic properties.

Key Challenges

To maximize the clinical potential of antibody-drug conjugates (ADCs) in cancer treatment, three critical challenges must be tackled in the future: refining ADC toxicity profiles, identifying biomarkers for prediction and resistance, and evaluating the effects of sequencing ADCs with overlapping targets or payloads that share similar mechanisms of action.

Competitive Landscape

Several companies are integral to the research, development, and manufacturing of antibody-drug conjugates (ADCs). Among the most influential in ADC production are Pfizer, AstraZeneca, Gilead Sciences, and Seagen. Pfizer Inc. was among the pioneers in antibody-drug conjugate (ADC) development and remains committed to advancing antibodies for this purpose. Like AstraZeneca, its primary focus is on oncology drugs. Gilead Sciences, ranking as the second-largest patent filer for ADCs, continues to be a key player in ADC innovation. Additionally, significant progress in treating metastatic urothelial cancers has resulted from a collaboration between Seagen and Astellas Pharma.

Conclusion

Decades of academic and industry-driven research have led to the successful development of diverse ADC therapies, benefiting tens of thousands of cancer patients. The approval of 11 ADC drugs, along with promising clinical results from emerging candidates, has further heightened interest in this complex yet rapidly evolving field. Fortunately, numerous studies have shed light on the key factors influencing ADC behavior. Establishing robust evaluation methods for each ADC component, both in vitro and in vivo, is essential. Advancing the identification and validation of new antigens and antibodies, optimizing payload toxicity, and designing linkers that balance stability with effective payload release are crucial steps for the next generation of ADCs. With ongoing research and innovation, future ADCs are expected to bring even greater advancements in targeted cancer therapy.