Antibody-Drug ​Conjugates: A Potential Replacement for Chemotherapy?

Updated June 18, ⁣2024

Chemotherapy has been a vital cancer treatment for decades. ‍However, the pharmaceutical industry is exploring antibody-drug ⁤conjugates (ADCs) as a potential replacement, offering targeted therapy with fewer ⁣harsh side effects.

adcs deliver potent‌ chemotherapy directly to cancer cells, sparing​ healthy cells. Companies like AstraZeneca, Daiichi Sankyo, Pfizer, Merck, Gilead‍ and Johnson & Johnson are investing heavily in ADC⁤ development.

While ADCs have shown promise, ‍experts caution that it will take years before they can broadly replace⁤ chemotherapy. ⁢Refinement of the treatments is ⁢still needed.

Dr. John ‌Heymach, chair‌ of⁢ thoracic/head and neck medical oncology at MD Anderson Cancer Center, noted that‍ while there have been successes, the early hopes of ADCs fully eliminating the need ​for⁣ chemotherapy have not yet been fulfilled.

However, some companies believe ADCs​ can‍ replace chemotherapy in ‍specific situations. David Fredrickson,‍ executive vice⁢ president of ⁤AstraZeneca’s oncology business, stated⁢ that they are​ leading the way in establishing ADCs as a​ precision-based approach to replace ⁢classic chemotherapy.

AstraZeneca’s Enhertu showed promising data at the 2025 American Society of Clinical oncology ⁤(ASCO) annual meeting, along with positive results from other companies on existing and experimental ADCs.

Since the first ADC was​ approved ​in 2000, the field has⁢ progressed significantly. ‍Over a dozen adcs are now approved in the U.S., ​becoming preferred‍ treatments for certain tumors. Hundreds more are in development. Pfizer’s ⁣$43 billion acquisition⁣ of ⁢Seagen in 2023 highlights the industry’s interest in ADCs.

The ‍ADC market could reach $31 billion ‌of the $375 ⁤billion worldwide cancer market in 2028, according to Evaluate.

Challenges remain, including controlling ⁢the release of the toxic chemotherapy payload to avoid affecting healthy cells. Identifying the ‍right cancer-causing proteins‌ to target and developing new⁢ payloads are also crucial.

The industry⁢ is​ addressing these issues by developing ​next-generation ADCs and combination regimens. AbbVie, such as, has a newly​ approved therapy that targets new proteins,​ while others‌ use linker platforms for better control⁣ of payload release.

Dr.Jeffrey Infante, global head of early clinical development, translational research and ⁢oncology at Johnson & Johnson, acknowledges the⁢ challenges but emphasizes the field’s rapid‍ growth and ⁤continuous improvements.

big progress in ADCs

ADCs ‌typically consist of an ‍antibody targeting a protein on cancer cells, a chemotherapy payload, and a linker connecting them. ‍The antibody guides the ADC to the⁤ cancer cell, where the linker releases ‍the chemotherapy to kill the cancer from within.

Newer ADCs like Enhertu deliver more chemotherapy⁣ per dose and use linkers that release the drug only inside tumors. Enhertu‌ can also kill nearby cancer cells​ with​ lower levels of HER-2,a important advancement.

Enhertu is approved in the ⁣U.S. for certain ​breast, lung, ‌and gastric cancers, with 2024 sales topping $3.7 billion. Data presented at ASCO could expand its use and change ‌breast cancer treatment.

In a late-stage trial, Enhertu stalled the growth of a common type of breast cancer ⁤by over a year when used as an initial treatment, compared to a standard regimen containing chemotherapy. AstraZeneca and daiichi Sankyo are seeking approval ⁤for this use.

Ken Keller, Daiichi Sankyo’s CEO‍ and head of⁢ oncology business, believes that Enhertu data ​shows “you can replace and knock the chemotherapy out.”

Heymach said the ‌Enhertu data “is the type of clear, major advance that we’d like to see more ‌often, where this ADC could become the ‌first option for patients.”

Other ADCs are also ‍progressing. Pfizer’s ⁤Adcetris, acquired from Seagen, is⁤ approved as an initial treatment with chemotherapy for certain lymphomas, generating almost $1.1 billion ⁢in sales in 2024.

Padcev⁢ from Pfizer and Astellas‍ Pharma,approved with Merck’s Keytruda ‍as a ⁢first-line bladder⁢ cancer therapy,booked ‌$1.69 ⁢billion⁢ in sales last year. Keytruda is an immune checkpoint inhibitor that helps immune cells​ recognize and kill cancer cells.

Gilead’s Trodelvy, an ADC that ⁣took in $1.3​ billion in revenue in 2024, also garnered⁣ attention at ASCO. as a first-line treatment, Trodelvy combined with Keytruda lowered the risk of disease progression by 35%⁢ in patients with an aggressive type of breast⁢ cancer in a late-stage trial.

What’s next

The ⁤future of cancer treatment may involve ADCs playing a more prominent role, potentially replacing⁣ chemotherapy in certain settings. Ongoing research ⁤and development efforts are focused on improving ADC technology and expanding their application to‍ a wider range of cancers.