1.10 Have ADCs peaked?

Have antibody-drug conjugates peaked—or is there more innovation to come?

Antibody-drug conjugates (ADCs) are complex products, and it has taken the field some time to iron out some of the difficulties that hampered their initial development. 

The basic idea is simple—by attaching a cytotoxic payload to an antibody that targets a protein expressed (ideally uniquely) on the surface of cancer cells, you can combine the exquisite specificity of antibody-based therapies with the potency of chemotherapeutic agents. But attaching (conjugating is the technical term) a cytotoxic molecule to an antibody, via a linker (several types exist), is not a trivial task. In the early days of ADC development, developers had little control over where that attachment took place—or, indeed, how many such conjugations occurred. Ensuring that the payload was only released once the ADC recognized the cancer cell and was taken up by it was another parameter that was difficult to optimise. 

The resulting products had inconsistent safety and efficacy profiles, therefore, and often unacceptable levels of toxicity. AstraZeneca’s eye-catching megadeal in 2019 with Daiichi Sankyo, which gave it rights outside Japan to Enhertu (trastuzumab deruxtecan), for cancers that express human epidermal growth factor receptor 2 (HER2), marked the beginning of a maturation stage for the ADC sector. It gained its first approval, in HER2+ breast cancer, later that year. The number of approved products has mushroomed since then to over a dozen. 

Although there have been no ADCs approved during 2023, several large transactions show that the category is now a major priority for large pharmaceutical firms. Pfizer is paying $43 billion to acquire Seagen, an early pioneer of the space, while Abbvie is picking up ImmunoGen for just over $10 billion, and a plethora of licensing deals were also agreed this year. ADCs are not curative agents, although in clinical trials they have offered meaningful survival gains to many cancer patients. There remains a compelling need for further innovation in this space, particularly in optimizing the trade-off between toxicity and efficacy.
 

Companies mentioned in this episode: 

Pfizer, Celltech (now UCB), Genentech, Seagen, AstraZeneca, Daiichi Sankyo, Abbvie, ImmunoGen, GSK, Immunomedics, Gilead Sciences, Biontech, DualityBio, Medilink Therapeutics

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