Read Act 1: The great reappearing act: Antibody-drug conjugates' triumphant return
Read Act 2: The great reappearing act: ADCs' new bag of tricks
With many of the initial kinks smoothed, pharma’s stage has been lit up with ADC deal-making. According to data from Citeline's Biomedtracker, between January 2018 and March 2023, there were approximately 100 publicly disclosed licensing deals that included ADC assets.
Pharma has its wallet open to M&A as well. Just months after Immunomedics won approval for its first ADC, Trodelvy, in 2020, Gilead snapped up the company for $21 billion. Shortly after, Merck plunked down $2.8 billion to acquire VelosBio with an eye on its mid-stage ADC geared toward blood cancers and solid tumors. Rumors began swirling in 2022 that Merck was also in advanced talks to buy ADC leader Seagen, but ultimately it was Pfizer that ponied up a whopping $43 billion this past April to take over the company — and its three commercialized ADCs.
Pfizer CEO Albert Bourla called the deal a “major, major move” for Pfizer in oncology, elevating the company from “middle in the pack competitor” to “quite a high position.”
The deal also speaks volumes about the ADC space: Pfizer, one of the biggest pharma companies in the world, already armed with 24 approved cancer meds, is looking to boost its competitive status in oncology — and has chosen ADCs as the path to get there.
Seagen was the first company to commercialize an ADC after Pfizer had pulled Mylotarg from the market when Adcetris, a CD30-directed ADC, won FDA approval in 2011. Adcetris also has the distinction of being one of just a handful of ADCs that have achieved the coveted blockbuster status, adding market validity to the modality.
Adcetris was first approved in two small patient populations — Hodgkin lymphoma and systemic anaplastic large cell lymphoma — in situations where patients had relapsed or become resistant to frontline treatment. Seagen continued to test the drug in trials, which resulted in both expanded approvals to include frontline treatments and approvals in new indications.
Sterling’s McKee points to the approval trajectory of Adcetris as a model for how smaller biotechs can approach commercialization.
“We’re definitely seeing strategies where drugmakers are getting into difficult indications initially, building up a safety profile and then sort of walking back to broaden the applications,” says McKee.
Expanding ADCs to earlier lines of treatment or more broadly against different tumor types also demonstrates a path towards profitability, which will be key to maintaining the current market buzz.
ADC encores
While ADCs are currently the headliners, leaders in the space point out that they are just one modality under the widening umbrella of bioconjugates.
“There is much more than the traditional ADCs,” says Lonza’s Bertholjotti. “New types of novel formats will pop up and that’s also how I see the market further evolving.”
‘Bioconjugates’ encompass any type of treatment that links small molecule drugs to more complex biologics. This includes drug types that have already notched some approvals, such as peptide drug conjugates (PDC) and radionuclide drug conjugates (RDC), as well as more nascent modalities such as antibody-oligonucleotide conjugates (AOC) or immune-stimulating antibody conjugates (ISAC).
According to Sterling’s McKee, the bioconjugates space as a whole is on the rise.
“We’ve seen an increase in deals and in success in conjugated actives being delivered,” says McKee. “The term ‘ADC,’ in its purest form as a descriptor for cancer targeting and direct killing agents, is not enough anymore. Now we are using a wide range of targeting moiety, ranging from peptides, through protein binding domains, and various antibody formats; some targeting once cancer antigen, some now targeting two different cancer antigens for even better specificity. So really it’s a growth in conjugated modalities overall.”
Awe-inspiring
ADCs are far from the first treatments to be dubbed ‘magic bullets’ — Ehrlich used the term to describe his search for a cure for ‘sleeping sickness,’ malaria and syphilis. In the ‘80s, mAbs were celebrated as ‘magic bullet drugs’ because of their capacity for specificity.
But most agree that the future of medicine involves delivering the right treatments to the right patients at the right time — and ADCs have proven themselves a worthy act.
“The goal of drug delivery is ‘precision medicine’ and ADCs are a major advance in that direction. With a targeted approach, patients are likely to stay on therapy longer with improved outcomes and better quality of life,” says ADC Therapeutics’ Mallik.
As more bioconjugates work their way through the clinic, ADCs will likely not be the pharma industry’s last magic bullets, either. But buoyed by market success and deal-making confidence, antibody-drug conjugates have seemingly become a permanent part of the oncology show.
“A lot of factors speak to the evolution of the field, but the deciding factor will be the patient benefit. And we’ve clearly seen that, with the approvals, ADCs make a huge difference to patients and have potential to make even greater difference to a significant population of very sick patients,” says MilliporeSigma’s Bucerius.
While the success of ADCs is firmly grounded in strong science and manufacturing expertise, to those patients in need of care, the outcomes have been nothing short of magical.
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