RE:ADCs - excess toxicities & unfavorable risk-benefit profiles Antibody-drug conjugate (ADC) technology is not new. The first ADC, Pfizer's Mylotarg, reached the market two decades ago. The field has undergone slow but transformative enhancements.
“ADC development has historically not been without its setbacks,” Datamonitor Healthcare analysts noted in a 2019 report. The concept of delivering a potent cytotoxic payload directly to tumor cells and causing minimum damage to non-tumor cells was viewed as a significant advance towards precision medicine, but it proved difficult to translate into the clinic. Now the field is coming of age, with more products on the market and a busy pipeline channeling new candidates into later stage trials. The number of big-name players in the ADC space is also on the rise.
Next-generation ADCs are also entering the pipeline, even as the first generation of products are still securing global approvals primarily because ADCs typically have less “off-target” action and less toxicity than conventional chemotherapy treatment.
According to data from Pharmaprojects, there are 428 ADC drugs in the pipeline, with the majority of assets in preclinical development.
In March 2023 Pfizer announced it would pay US$43 Billion for ADC developer Seagen. Recent discussions, following Pfizer’s bid for Seagen, have focused on the question of biosimilar competition for ADCs, and importantly whether these complex drugs are almost immune to biosimilar competition.
In the days before Pfizer’s deal was announced, Seagen’s CEO David Epstein had also laid bare the hurdles for biosimilar sponsors, both regulatory and development. “First, the regulatory path has to be determined. It doesn’t exist today.” He continued, “I don’t think, for example, just injecting an ADC and then taking a blood level is going to tell you whether the drugs are the same or not.”
Nevertheless, he suggested, “someday, I would imagine there’s a biosimilar that can be made.” But “it’s not any time soon.”
Ameet Mallik, CEO of ADC Therapeutics and former head of the biosimilars unit at Sandoz, told In Vivo that at one point people also thought biologics would be immune from copy products. However, he said the process to create an ADC was very complicated. “I would never say never… but the barriers to producing a generic ADC are much higher than what it takes to produce a biosimilar.” He added that generic and biosimilar companies would need to develop their current capabilities to be able to produce ADC copy products.
ADC Therapeutics’ Mallik expects to see deals become more focused. He said there were two main types of collaborations: companies teaming up to access expertise or products, or deals to license linker, conjugation or toxin technology. “Those are the ones where it will be interesting to see them play out. Getting an ADC right is difficult. There will be a lot of learnings from those deals,” Mallik said.
Mallik highlighted that not many companies had been able to bring ADCs to market, so far.
“Having a commercial product, also with the potential for expanding earlier lines of treatment, you could see a successful a path towards profitability. As an industry, we've been working with a small set of payloads up to this point and the number of potential payloads, both toxin and not toxin, such as immunostimulants, is just expanding.” said Mallik
Mallik added that he saw a world of potential for the future of ADCs. For example, the future could include bi-specific ADCs or ADCs with dual payloads.
The CEO wants to see continued improvement in ADC technology to expand the therapeutic index and reduce systemic toxicity when treating cancer.
Enter ONCY's pelareorep in combination with ADCs.