San Francisco—Nearly all top cancer drugmakers have struck deals in the sizzling antibody-drug conjugate field—but not Novartis. On Monday, the Swiss pharma’s CEO Vas Narasimhan explained how he's resisted the temptation.
The answer is radioligand therapies, Narasimhan said Monday during the 2024 J.P. Morgan Healthcare Conference in response to a question from Fierce Pharma.
“We have a long history within research of ADCs, but we have not been successful,” Narasimhan said. “To be clear, part of our focus strategy is looking at places where we think we can create long-term sustainable leadership. And we are investing in radioligand therapies.”
ADCs and radioligand therapies are similar in that both technologies act as guided missiles. For ADCs, the guiding force is an antibody, and the cancer-killing payload is a chemotherapy. A radioligand therapy uses a ligand to target cancer cells and kills them with a therapeutic radioisotope.
Radiotherapies may have a safety edge compared with some ADCs, Narasimhan argued.
“We believe that the therapeutic index on radioligand therapies, when you find the right target, gives you a pretty wide window to get a therapeutic effect without some of the safety issues,” the Novartis CEO said.
One of the most concerning side effects with ADCs is interstitial lung disease (ILD), a potentially life-threatening condition marked by scarring of the lungs. A phase 3 non-small cell lung cancer clinical trial of AstraZeneca and Daiichi Sankyo’s TROP2 ADC, Dato-DXd, recently reported seven ILD deaths that were determined to be drug-related. In four of those cases, disease progression was deemed the primary cause of death.
“If you can avoid that in radioligand therapy but still get that high efficacy—and given we have completely unconstrained supply now with all the investments we’ve made—we think that’s a better place to focus our capital versus over-indexing on ADCs,” Narasimhan said.
Novartis’ radiotherapy portfolio is led by PSMA-targeted Pluvicto and SSTR-aimed Lutathera. The company is trying to move Pluvicto into earlier treatment of prostate cancer.
Besides a regulatory delay for Pluvicto, Narasimhan acknowledged that the delivery of radiotherapies can be a constraint early in expansion process because of the complexity of making these therapies. To eventually realize Pluvicto’s potential to reach more than $3 billion in peak sales, Novartis will need to expand its treatment center network from about 300 institutions today to around 500, Narasimhan said.
Meanwhile, Novartis is working on other actinium-based compounds, which could give the company the next wave of drugs in the prostate cancer space, Narasimhan noted. It also has clinical candidates with FAP, GRPR and integrin as targets.
Novartis got Pluvicto from its $2.1 billion acquisition of Endocyte in 2018. It recently added more radiotherapy capabilities from a licensing deal with Clovis Oncology and a multi-target collaboration with Bicycle Therapeutics.
Other deals in cell and gene therapy and RNA therapeutics rounded out Novartis’ three novel technology platforms beyond traditional chemicals and biologics.
Still, Novartis remains the only major cancer drug developer that doesn’t have an ADC deal.
Last year, Pfizer splashed $43 billion to purchase ADC pioneer Seagen, and AbbVie is in the process of acquiring ImmunoGen for $10 billion.
Merck has licensing deals with Daiichi and China’s Kelun Biotech, and GSK has teamed up with Mersana Therapeutics and Hansoh Pharma.
Following ADC deals with Eisai, Tubulius and Orum Therapeutics, Bristol Myers Squibb in December paid $800 million upfront for an early-stage ADC from SystImmune.
Eli Lilly last year bought Emergence Therapeutics and Mablink Bioscience.
For its part, Johnson & Johnson jumped on the scene in late December, first snatching up a TROP2-directed ADC from South Korea’s LegoChem Biosciences in a deal potentially worth $1.8 billion. Then on Monday, the New Jersey pharma unveiled an agreement to buy out ADC specialist Ambrx Biopharma in full for $2 billion.
Roche also joined the ADC deal spree in late 2023 with a deal with China’s MediLink Therapeutics around a c-MET ADC. That collaboration is worth up to $1 billion.
Even BioNTech, which doesn’t yet have a commercial oncology product, has penned ADC deals with China’s Duality Biologics and MediLink. BeiGene last year also got an ADC from Duality.