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The ADC market: Hot – or too hot to handle?

Antibody-drug conjugates (ADCs) are a unique class of drug compound, comprising a monoclonal antibody (mAb), a linker, and a cytotoxic payload. Together, these make it possible to target tumors with far greater specificity than with traditional forms of treatment.

“This unique design enables ADCs to achieve ‘targeted chemotherapy’ and provides advantages over conventional chemotherapy and targeted therapies”
– Lei-Jie Dai, Fudan University Shanghai Cancer Center

The ADC market has been one of the fastest-growing within the whole pharma industry in the last eight years. From three approved drugs worth around $1 billion/year in sales in 2015, it grew to 13 worth $10 billion/year in 2023. Evaluate, a Norstella company forecasts that it will rise to $28 billion/year by 2028.

total-value-of-adc-graph

This growth has been driven largely by oncology, for indications including breast cancer, ovarian cancer, hairy cell leukemia, lymphoma, and multiple myeloma. Although other indications are emerging, oncology will remain the driving force.

Key ADC drug launches, 2017-2022

2017
Besponsa (Pfizer, refractory acute lymphoblastic leukemia)

2018
Lumoxiti (AstraZeneca, hairy cell leukemia)

2019
Enhertu (Daiichi Sankyo/AstraZeneca, breast & gastric cancer)
Padcel (Astellas, urothelial cancer)
Polivy (Roche Genentech, diffuse large B-cell lymphoma)

2020
Trodvelvy (Gilead Sciences, metastatic triple negative breast cancer & metastatic urothelial cancer)
Blenrep (GSK, multiple myeloma)
Akalux (Rakuten Medical, head and neck cancer)

2021
Zynlonta (ADC Therapeutics, large B-cell lymphoma & high-grade B-cell lymphoma)
Tivdak (Genmab/Pfizer, cervical cancer)
Aidixi (RemeGen, HER2 & gastric cancer)

2022
Elahere (AbbVie, ovarian cancer)

The year 2023 saw a boom in M&A and partnerships in the ADC sector – three times more than in 2022 and nine times more than in 2019 – as major pharma companies sought to acquire and/or license ADC technology. This has continued into 2024.

Key deals in ADCs, 2023-2024

Pfizer buys Seagen – $43 billion,
AbbVie invests in Immunogen – $10.1 billion
Merck & Co. buys stake in three Daiichi Sankyo ADCs – $4 billion initially, potentially rising to $22 billion
Johnson & Johnson buys Ambrx Biopharma – $2 billion
Roche licenses in MediLink pipeline asset – up to $1 billion

More can be expected in the years to come as the ADC pipeline is extremely promising. There are over 150 clinical-stage programs ongoing, with 12 currently in Phase III. Daiichi Sankyo alone is forecast to earn almost $10 billion in 2028 from Enhertu, which is already approved, and datopotamab deruxtecan, which has had promising results in trials.

Contract development and manufacturing organizations (CDMOs) are also investing in capabilities to serve this growing market. Among those making recent announcements have been Samsung Biologics, Lonza, Fujfilm Diosynth Biotechnologies, Porton Pharma Solutions, and Sterling Pharma Solutions.

The wave of investment means that ADCs have become a sector for large players. One biotech that had raised nearly $200 million reported in September 2023 that it had been priced out of ADC licensing because of the prohibitive cost of early-stage assets

Recent years have seen major technological advances in all three parts of the ADC. As a result, their application has widened, their therapeutic efficacy has improved even further, and the incidence of adverse effects has fallen.

Mechanism of next-generation ADCs

Humanized & engineered mAbs → Higher tumor specificity
Enzyme-specific cleavable linkers → Enhanced selective payload release
Membrane-permeable cytoxic drugs & higher drug-antibody rate → Bystander effects & enhanced efficacy

There is also growing interest in ADCs designed to stimulate the immune system, such as toll-like receptors (TLRs) and stimulator of interferon genes (STING) agonists. Bispecific ADCs that can target two different antigens on a tumor simultaneously are also emerging rapidly.

“After several decades of platform development, ADCs have very much entered the mainstream for oncology R&D. Standout clinical trial data and a deal-making frenzy make the ADC space one of the most dynamic in the industry, and the class is set to provide a huge impetus to growth within oncology. ADCs are also now moving beyond tried-and-tested targets such as HER2 into novel mechanisms, where there is strong hope for new personalized cancer treatments.”
– Daniel Chancellor, VP Thought Leadership, Norstella

For more information download the full Antibody Drug Conjugates Report.

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