‘Guided missile’ drugs pack a big anti-cancer punch
DOZENS of drug makers are conducting human trials for a record 89 therapies that pair antibodies with toxic agents to fight cancer, evidence of renewed confidence in an approach that has long fallen short of its promise, an analysis shows.
These antibody-drug conjugates, or ADCs, from companies including AztraZeneca and GlaxoSmithKline, are described by researchers as “guided missiles” packing a powerful anticancer punch.
They are engineered to zero in on tumours and then release cytotoxins that deliver up to 10 000 times the potency of standard chemotherapy, while minimising damage to healthy tissue.
The approach has for decades been a major biotech industry focus. Many experimental ADCs, however, failed due to the complexity of pairing the right antibody with the appropriate toxic agent. Some were abandoned as too weak; others were too harmful.
From 2000 to 2018, only five ADCs won approval. Just one, Roche’s Kadcyla, approved in 2013 for breast cancer, has surpassed $1 billion (R14bn) in annual sales after data last year showed it boosted disease-free survival for some patients compared with the standard treatment, Roche’s Herceptin.
“What we’re seeing now are the benefits of the science becoming mature,” said ADC pioneer Chris Martin, chief executive of Switzerland’s ADC Therapeutics.
“It took at least a decade, more like 15 years, to really begin to turn the art into a science.”
London-based Beacon advises drug makers on targeted therapies, helping them decide whether to pursue prospective drugs or redirect efforts.
Massachusetts-based ImmunoGen, hit by past trial failures, got a lift in December for its ADC against ovarian cancer when the FDA indicated it may become a candidate for accelerated approval.
The surge in ADC investment has been fuelled in part by improvements in the so-called “linker” technology that binds the antibody to its cancerkilling toxins, keeping them stable in the circulatory system until the poison can be unleashed on the targeted tumour.
“What we see over time at Lonza is a good request for capacity,” said Iwan Bertholjotti, Lonza’s bioconjugate commercial development head. “That’s a good sign that the market is booming.”
AbbVie in August abandoned its ADC candidate Rova-T after flunking a lung cancer trial and wrote off most of the $5.8bn it paid for the drug’s developer, Stemcentrx, in 2016.
Roche, which helped pioneer ADCs with Kadcyla and Polivy, has also backed off. In 2013, the Basel-based company had about a dozen experimental ADCs.
Today only one remains and it is being developed for staph infections, not cancer.
“We have shifted our technology priorities,” Roche chief executive Severin Schwan said. “Maybe others will be luckier, but we failed to master the complexity.”
AstraZeneca aims to do just that. In March last year the Cambridge, England-based drug maker struck a $7bn deal with Japan’s Daiichi Sankyo for rights to Enhertu, getting $1.35bn up front, and more if it challenges Roche drugs’ dominance in breast cancer.