Antibody-drug conjugate created a new wave of targeted cancer therapies ushering a new era in cancer treatment. Just last week AstraZeneca and Daiichi Sankyo’s Enhertu was approved in the United States for treatment of breast cancer, lung cancer and gastric cancers. This novel therapy allows for a more potent dose of chemotherapy to be delivered than other ADCs. It accomplishes this with a clever linker that ensures the drug is only released in tumors. With the ADC space re-energized, and with great hopes from the pharmaceutical industry for new revenue streams from ADC therapies, ADC development is becoming frenetic.
In 2024, Gilead’s Trodelvy, another ADC, an anti-cancer ADC, earned $1.3 billion in sales. Meanwhile, Pfizer and Astellas Pharma’s Padcev, approved in conjunction with Merck’s Keytruda as a first-line bladder cancer therapy, achieved $1.69 billion in sales last year. AstraZeneca expects Enhertu to bring in up to $3.7 billion in sales by 2024. This projection emphasizes the rapidly growing market for these advanced therapies.
Since then, more than a dozen ADCs have been approved in the U.S. Today, they’re rapidly becoming the best treatment choice for certain tumors. With hundreds of further ADCs in development, promising an exciting pipeline of advanced cancer therapies, their potential can be heard. The entire market for cancer treatments is projected to reach $375 billion by 2028. Within this, antibody-drug conjugates (ADCs) might bring in a jaw-dropping $31 billion.
Even given these promising developments, hurdles still exist with respect to getting the most out of these therapies. GSK announced that it is withdrawing its U.S. application for an ADC directed against HER-3. This bombshell announcement followed the drug’s failure to demonstrate any increase in overall survival in an advanced stage trial for lung cancer. GSK’s Blenrep has shown efficacy success in two pivotal trials. It was particularly effective in combination with other therapies, as an option for patients with previously treated blood cancer. The company is projecting peak annual sales of as much as £3 billion ($3.97 billion) for Blenrep.
Even in the rapidly evolving ADC space, companies such as BioNTech and Eli Lilly are combining therapies in novel ways. BioNTech is developing ADCs to simultaneously target two different proteins on cancer cells. At the same time, Eli Lilly has shifted its focus on ADCs toward ones that use non-chemotherapy payloads. Johnson & Johnson have been leaders in this space. They claim to be inventors of a number of experimental ADCs that employ a “very stable” linker platform.
The major players within the industry see ADCs as a precision-driven cancer treatment that cuts out the need for traditional and often toxic chemotherapy. David Fredrickson stated, “We are leading the way towards establishing ADCs as a precision-based approach to replace classic chemotherapy.”
Dr. Jeffrey Infante acknowledged the challenges that lie ahead: “It’s been hard. We haven’t optimized everything perfectly yet. I think that the field is still growing fast, and it’s making improvements every year.” This sentiment seems to be driven by the optimism surrounding ADC technology and the expectation of continued advancements.
Though successes have undoubtedly been impressive, some experts warn not to overshoot on the promise of ADCs to put chemotherapy out to pasture entirely. Dr. John Heymach remarked, “I think we’ve had some successes in the space, but I think the early hopes that they would sweep away the need for chemotherapy have mostly been unfulfilled so far.” This view further emphasizes the need for continued research and development to optimize these novel therapies.
As ADCs become more firmly established within treatment arsenals, researchers are working to perfect their use. Ken Keller emphasized the momentum behind these therapies: “We’re moving this drug earlier and earlier, and the magnitude of benefit gets bigger and bigger.” The aim is for these therapies to be brought into much earlier-stage arenas, where cure of cancer is the major objective.
Dr. Dietmar Berger highlighted the need for careful consideration of patient populations that may benefit most from these therapies: “You need to learn from the different studies and see the exact populations that might benefit.” This analysis aims to enhance the efficacy of ADCs and ensure they serve the patients who will gain the most advantage.
What’s really exciting is the favorable combined use of ADCs with other existing therapies. Chris Boshoff explained, “When we combine them, we see increased response rates, increased progression-free survival, and in the cases where we have tested, an increase in overall survival.” Taken together, these findings make a strong case for additional research on combination therapy approaches.
Annemarie Hanekamp expressed excitement about these developments: “We can then combine these two powers together and that’s truly exciting.” The unprecedented potential synergy between the oncology therapeutic modalities with immunotherapy could mitigate or abolish the burdens of existing cancer therapies.