Overview
Novartis said on Sunday that initial results from a 101-patient study of its experimental actinium-based radiopharmaceutical showed signals of anti-tumour activity in prostate cancer, including in patients who had received the company’s existing radioligand Pluvicto. The company presented the data at the American Society of Clinical Oncology meeting in Chicago.
Trial outcomes
The study reported that among patients previously treated with Pluvicto, 52.5% experienced a drop in prostate-specific antigen, or PSA, of at least 50% while receiving the actinium-based therapy. Elevated PSA level is a common marker for prostate cancer. Response rates were stronger in patients without prior Pluvicto exposure: more than 85% of trial participants with no prior treatment saw PSA fall by half. For patients who had received chemotherapy first, 58.8% recorded PSA declines of at least 50%.
Safety considerations
While the efficacy signals drew attention, analysts and company executives highlighted safety as a critical area for further study. TD Cowen analysts said the early data point to clear efficacy but cautioned that managing adverse events - notably high rates of dry mouth and severe anemia - will be important. Novartis Chief Medical Officer Shreeram Aradhye said larger trials are required to determine how severe those side effects may be and whether they are reversible, particularly if the experimental drug moves into earlier lines of treatment.
Company strategy and pipeline
Novartis is expanding its commitment to radioligand therapies, which deliver radioactive payloads directly to cancer cells. The company is advancing two late-stage studies of the experimental actinium drug. Radioligand approaches now represent nearly 40% of Novartis’ cancer R&D investments, according to the company.
Novartis already markets Pluvicto and Lutathera, which together generated $2.8 billion in sales last year. Radiopharma has become a rapidly growing segment in oncology, with multiple large drugmakers having acquired radio-drug developers in recent years.
Actinium versus lutetium
The company explained a technical distinction between the isotopes: Pluvicto uses lutetium-177, a beta-emitting isotope, while the experimental agent employs actinium-225, an alpha emitter. As Aradhye put it, "The difference is that much higher amounts of energy (are) delivered across a much smaller distance, and the potential for greater efficacy." The different emission properties are central to why the actinium agent could perform differently from lutetium-based therapies.
Supply and production
Some analysts have raised concerns that current actinium-225 supply may not be sufficient to meet growing clinical demand. Novartis said it is planning around future isotope needs and in February entered a long-term supply agreement for actinium with U.S.-based medical isotope producer Niowave.
Next steps
Novartis is moving ahead with larger, late-stage trials to better establish both the efficacy and the safety profile of the actinium-based drug. Those studies will be critical to determine how the therapy could be positioned relative to existing radioligand options and what safety mitigation strategies might be required.
Data limitations
The information available stems from early-stage data presented at a scientific meeting and reflects outcomes from a 101-patient trial. Novartis and outside analysts emphasize that larger trials will be necessary to fully characterize both benefit and risk.