ADCs are in focus. Here’s where AstraZeneca, AbbVie hope to take the field next.

11 Jun 2024
www.biopharmadive.com
ImmunotherapyADCASCODrug Approval
Pharmaceutical companies employ many different strategies when building their cancer drug pipelines, but one recent commonality among them is a belief in the future of targeted therapies known as antibody-drug conjugates.
Many of the leading cancer drugmakers have at least one or two antibody-drug conjugates, or ADCs, in development. Others, such as Pfizer, Johnson & Johnson and Merck & Co., have used buyouts or partnerships to build an ADC portfolio.
One of the best-selling ADCs on the market is AstraZeneca and Daiichi Sankyo’s Enhertu, which brought in combined sales of $2.5 billion in 2023, almost double the year before. The two companies formed a $7 billion alliance around Enhertu in 2019 and since then, the drug has secured multiple approvals and changed the way some breast cancers are treated.
Over that time, AstraZeneca has made ADCs a more substantial part of its overall pipeline alongside radiopharmaceuticals and immunotherapies, giving the company many potential combinations to work with, said Carlos Doti, vice president and head of medical affairs for its U.S. oncology division.
“We started our ADC journey with the Daiichi partnership, and now we’re bringing seven or eight different molecules from our own platform,” Doti said.
Since the approval of the first ADC, Mylotarg, in 2000, researchers have improved the drugs’ capabilities by trying different components and changing the way they are linked together. As a result, newer ADCs could be used for more tumor types, and alongside other therapies, such as drugs that spur the immune system to fight cancer.
“ADCs can sort of be like a choose-your-own-adventure — you have all these different [tools] available to you, and now you can identify where there’s unmet need,” Doti said. “What was clear from [the American Society of Clinical Oncology’s annual meeting this year], the combination of ADCs and [immunotherapies] will change the first line of treatment by combining that immune system enhancement and directed therapy together.”
AstraZeneca, for instance, presented results suggesting Enhertu should be used ahead of chemotherapy in a common type of advanced breast cancer, and in a broader group of patients. That finding is a step forward in a broader strategy by the company to use ADCs to supplant chemo in many tumor types.
But AstraZeneca is advancing other ADCs as well. The company has prospects in early clinical studies for lymphoma, leukemia, multiple myeloma and other malignancies. It is also aligned with Daiichi on datopotamab deruxtecan, which could be approved later this year for a form of lung cancer.
ADCs, which chemically link a targeting antibody to a tumor-killing toxin, were originally seen as a way to more precisely deliver chemotherapies. But AstraZeneca and its peers are moving beyond chemo to transport other payloads, Doti said.
“We’re improving our technology, and getting better antibodies to direct where it needs to go, and using linkers that only release the payload at the point of delivery,” Doti said. “So if you see a lot of things going on for us and others, it’s that we're not just working on delivering chemotherapy in the payload anymore.”
AbbVie’s oncology pivot
AbbVie’s cancer drug portfolio is headlined by treatments for blood malignancies. Recently, though, the big drugmaker has made solid tumors a focus, and ADCs are a key part of its plan. Last year, the company spent $10 billion on ADC developer ImmunoGen, giving it an ovarian cancer drug, Elahere, as well as a group of experimental medicines that complemented its internal ADC research.
“We’ve been working in the hematological space, but solid tumors have a larger unmet need in oncology, and so it was a natural next step,” said Pedro Valencia, vice president of AbbVie’s solid tumor pipeline and strategy. “One of the overarching strategies is a focus around ADCs, thinking about what we call the ADC toolkit with a series of novel antibodies, novel targets, novel payloads that can be first and also best in class.”
AbbVie is targeting tumors, like colorectal and small-cell lung cancers, that many other medicines haven’t treated well in the past. Some of its prospects also deliver a so-called TOP1 inhibitor to tumors, as Enhertu does.
“The reasoning is we have the ability to replace chemotherapy that has been used for decades, and … we’re trying to do that in colorectal, ovarian, non-small cell lung and small cell lung cancers,” Valencia said.
Although AbbVie is behind many other pharmaceutical companies in treating these types of tumors, Valencia said that gives it a chance to build franchises from scratch, as it did with Humira in immunology and Venclexta in blood cancers. “We like to be the newcomers,” Valencia said.
Like AstraZeneca, AbbVie envisions combinations of ADCs and other drug types as expanding the number of people who can benefit from treatment.
“If you combine ADCs and immunotherapies, for example, I see that as the next big wave to unlock patients who haven’t been unlocked before,” Valencia said.
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