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While major oncology pharmaceutical companies are employing a variety of strategies to build their pipelines, one recent element common to big pharma is a bet on antibody-drug conjugates, which many see as an alternative to chemotherapy.
Many of the big cancer drug makers have at least one or two ADCs in their development pipelines, and others, including Pfizer’s, are investing in big acquisitions to supplement their ADC funding. $43 billion acquisition of SiegenJ&J’s $2 billion Ambrx Biopharma deal and a series of acquisitions and partnerships from Merck & Co. are examples.
One of the best-selling ADCs on the market is Enhertu, a collaboration between AstraZeneca and Daiichi Sankyo, with combined sales of $2.5 billion in 2023That’s nearly double the figure from a year ago. Meanwhile, AstraZeneca has been beefing up its combination lineup, making ADCs a more important part of its overall pipeline alongside radiation and immunotherapy drugs, said Dr. Carlos Doty, executive vice president and medical chief of U.S. oncology.
“We started down the ADC path with our partnership with Dai-ichi Life, and now we have seven or eight molecules in our own platform,” Doty said. Since the first ADC, Mylotarg, developed by Pfizer subsidiary Wyeth, came to market in 2000, researchers have learned how to make the therapy more versatile by trying different antibodies and drugs, and by changing the way the two are linked together, Doty noted.
“We’ve refined the technology, developed better antibodies to direct it to where it’s needed, and we use linkers that release the payload only at the point of delivery.”
Dr. Carlos Doty
Vice President, US Oncology Medical Affairs, AstraZeneca
“ADCs are kind of a choose-your-own-adventure approach, so to speak. There are a variety of (tools) available to identify where there is unmet need,” Doti said. “What became clear (at this year’s ASCO annual meeting) is that the combination of ADCs and (immunotherapy) is going to transform frontline care by combining boosting the immune system with targeted therapy.”
With a view to studying the drug in earlier stages of treatment, AstraZeneca announced results from a late-stage study of Enhertu in patients with metastatic breast cancer, which could broaden the patient population and allow Enhertu to be used earlier in treatment plans.
AstraZeneca has ADCs in early-stage clinical trials in patients with cancers including lymphoma, leukemia, multiple myeloma, ovarian cancer and lung cancer, and also has datopotamab deruxtecan, an ADC, in later-stage trials targeting various types of breast and lung cancer.
Originally, ADCs were used primarily to deliver risky chemotherapy more precisely, but AstraZeneca and its peers are moving beyond chemotherapy to deliver drugs more effectively, Doty said.
“We’re improving the technology, developing better antibodies to get it where it’s needed, and using linkers that release the payload only at the point of delivery,” Doty said. “So when you look at a lot of the things that we and others are doing, you see that we’re no longer just trying to deliver chemotherapy with a payload.”
AbbVie’s Oncology Shift
AbbVie is best known as an oncology company with success in blood cancers, and has only recently pivoted to solid tumors. At the center of that strategic shift is a set of ADCs that AbbVie hopes will help it stand out in the solid tumor space, even as the company has to play a bit of catch-up.
“We’ve been active in hematology, but in oncology, the unmet need is greater in solid tumors, so it was a natural next step,” said Pedro Valencia, vice president of solid tumor pipeline and strategy at AbbVie. “Part of our overarching strategy is to focus on ADCs. We’re looking at what we call the ADC toolkit, with a set of new antibodies, new targets, new payloads, and looking at what will be first and best in class.”
AbbVie is targeting tumors such as colon cancer that previously could not be treated with other drugs. Increasing popularityIn an attempt to replace chemotherapy as standard of care, particularly in younger patients, AbbVie is using an ADC with a TOP1 inhibitor as its payload in an early-stage trial.
“The reason is that we have the ability to replace chemotherapy that has been used for decades and we are applying it to colorectal cancer, ovarian cancer, non-small cell lung cancer and small cell lung cancer,” Valencia said.
While AbbVie might be considered a relative newcomer to these tumor types, Valencia said the company is well positioned to build a franchise from the ground up, as it has done with blockbuster Humira in immunology and Venclexta in blood cancers.
“We like being the newbies. It reminds me of the underdog teams that go to the Olympics and are really dominant,” Valencia said.
Like AstraZeneca and many other oncology drug makers, AbbVie is developing multiple drug candidates and aiming to combine them to be most effective for patients with certain cancers, and Valencia said ADCs are ideally suited to that effect.
“For example, I think combining ADCs with immunotherapy will be the next big wave of treatments for patients who previously didn’t have treatments,” Valencia said.
