The 2024 US Market Landscape of ADCs
The antibody-drug conjugates (ADC) market has been rapidly moving forward in the last few years and is now entering their golden age, with the United States (US) leading the charge in both their research and commercialization.1 This year’s American Society of Clinical Oncology (ASCO) 2024 Annual Meeting in Chicago, Illinois saw several exciting updates from ongoing ADC pipelines, including those from big pharma companies like AbbVie and Pfizer .2 Considering the increasing prevalence of cancer and the need for more effective alternatives to chemotherapy, the market for ADCs is unsurprisingly projected to reach a whopping US$44.05 billion by 2029 from US$12.05 billion in 2024.1 ,3 ?
Representing a major advance in therapeutic engineering, ADCs consist of a single molecule that combines an antibody and a payload with linker or conjugation method before being delivered to their target in the body.1 Although these are not a new therapeutic platform in oncology, they’ve been experiencing a considerable revival recently, with over half of the 12 ADC approvals granted by the US Food and Drug Administration (FDA) coming out only in the last four years.4 ?
Assessing the Current US Market Landscape for ADCs
The ADC class of drugs combines the benefits of both small molecule and antibody drugs in an innovative approach rooted in precision medicine.5 This boosts their ability to target tumor signaling pathways or surface antigens with high specificity while sparing healthy cells. ADCs have already shown their potential against many treatment-refractory cancers, leading to 12 approvals by the US FDA for both solid tumor and blood cancer indications as of 2024.5 ,6 ?
Even though all these are approved for market use in the US, each ADC will have different efficacy and safety profiles, depending on their individual components and conjugation methods. In this 2023 review of approved ADCs by Gogia et al. , unique toxicities reported for some of these therapies included bleeding complications, ocular issues, skin rash, hyperglycemia, and pneumonitis/interstitial lung disease (ILD), among others.6
Next-Generation ADCs: Overcoming Key Challenges and Innovating for the Future?
The ADC therapeutic platform no doubt shows significant promise and success in treating various cancers, but we also have to consider the challenges which come with clinically developing these drugs. For example, eventual drug resistance is a major ongoing issue with ADC development, resulting in tolerance to certain payloads, antigen expression downregulation, and the intracellular trafficking pathway in tumor cells being modified.6 These drugs also have pharmacokinetic and pharmacodynamic profiles that are complex to navigate, with the antibody and cytotoxic payload components of an ADC having their own clearance pathways for researchers to work around.6 ?
To address these challenges and build on the success of existing ADCs, several novel ADC formats are currently in development, supported by the latest discoveries in linker and payload technologies.6 ,7 For example, probody-drug conjugates are showing better tumor specificity, while bispecific ADCs and dual-drug ADCs can potentially combat drug resistance and tumor heterogeneity.7 Combination therapy with ADCs and immunotherapy also presents alternative approaches to treating highly resistant tumors.8 Other ways to extend the value of these therapies in the future may also looking into the possibility of patient stratification and biomarker identification to maximize the benefits of ADCs.7
Now the race is on to continue developing the next wave of ADC agents, from immune-stimulating antibody conjugates and engineered toxin bodies to radioligand conjugates.8 With that, let’s take a look at key findings from ASCO 2024 for some of the promising ADC candidates to watch for in 2024 and beyond!
Novel Antibody-Drug Conjugate (ADC) Shows Promise in Advanced Colorectal Cancer
In their ASCO Meeting Abstract (Abstract 3000 ) presented at ASCO 2024, Kopetz et al. described the potential of M9140 in pretreated patients with advanced colorectal cancer .9 This novel ADC is one of the first antibody-drug conjugates with a topoisomerase 1 inhibitor payload designed to target the cell surface protein CEACAM5—which is expressed in over 90% of colorectal cancers.9 ?
When tested at different doses among 40 eligible participants, preliminary Phase 1 study data found that 42.5% of 40 patients treated with one of multiple experimental doses of M9140 reached stable disease, while 10% had a partial response.9 To assess its long-term safety and efficacy, M9140 will be evaluated in a randomized expansion study.9
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Novel ADC Offers Superior Survival Outcomes in Triple-Negative Breast Cancer
In OptiTROP-Breast01, a Phase 3 triple-negative breast cancer clinical trial presented at the 2024 ASCO Annual Meeting , overall survival (OS) and progression-free survival (PFS) were significantly longer with the ADC sacituzumab tirumotecan than with chemotherapy.10 These benefits were especially notable in patients with high TROP2 expression, which can be seen in >80% of triple-negative breast cancer cases.10 ?
Sacituzumab tirumotecan incorporates the same antibody as sacituzumab govitecan (Trodelvy?), the only TROP2 ADC currently approved for this indication, but it has a different payload and linker.10 ?
2024 ASCO Showcases New Data from AbbVie’s ADC Platform in Oncology
AbbVie presented the latest data from three ongoing clinical trials within their innovative ADC pipeline :11 ?
These new ADCs from AbbVie’s robust solid tumor pipeline have been designed to target the unique protein biomarkers c-Met and SEZ6, which are found in high levels in several cancers.11 With their high specificity for these targets, the data from several clinical trials showed these ADCs were able to induce targeted cell death, exhibiting positive survival outcomes and response rates in treated patients.11 ?
Pfizer’s ADCETRIS? Significantly Prolongs Overall Survival in Patients with DLBCL
ADCs were also among Pfizer’s wide portfolio of approved and pipeline therapies in oncology presented at ASCO 2024.12 In a late-breaker oral session on the Phase 3 ECHELON-3 study, ADCETRIS? (brentuximab vedotin) plus lenalidomide and rituximab was reported to reduce the risk of death by 37% in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).13 Compared with placebo plus lenalidomide and rituximab, improvements in overall survival were consistent with ADCETRIS? regardless of CD30 expression.13
Want to read the full ADC highlights from ASCO 2024? Download the infographic from the ASCO website here !
Concluding Thoughts
No doubt, the ADC therapeutic market has been seeing a remarkable surge in interest, with the recent ASCO 2024 Annual Meeting showcasing exciting updates, highlighting the growing importance of ADCs in cancer treatment. Despite challenges such as drug resistance and complex development processes, ongoing innovations in ADC technologies and formats are paving the way for next-generation treatments that are offering new hope in our fight against cancer.?
Keep up with the ADC revolution: Stay informed about the latest advancements in ADCs with ASCO Publications and learn more about the present and future of this platform here !
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