Novartis' Pluvicto Shows Promise in Hormone-Sensitive Prostate Cancer, Plans FDA Submission

Novartis has unveiled detailed data from its phase 3 PSMAddition trial, demonstrating that its radioligand therapy Pluvicto could significantly slow the progression of certain hormone-sensitive prostate cancers. The Swiss pharmaceutical giant plans to submit an application to the FDA by the end of the year, potentially doubling the number of patients eligible for the treatment.

Pluvicto's Efficacy in mHSPC

The PSMAddition trial results, presented at the 2025 European Society for Medical Oncology (ESMO) congress in Berlin, showed that Pluvicto, when combined with standard of care, reduced the risk of radiographic progression or death by 28% compared to standard of care alone in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC). The standard of care includes androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) such as Pfizer and Astellas' Xtandi.

While Novartis claims the improvement is statistically significant and clinically meaningful, it's worth noting that the magnitude of benefit is not as impressive as previously seen with Pluvicto in other indications or with other treatments in mHSPC. For instance, Xtandi demonstrated a 61% reduction in radiographic progression or death versus ADT alone in its pivotal mHSPC trial.

Dr. Scott Tagawa from Weill Cornell Medicine emphasized the importance of early, efficacious treatment in metastatic prostate cancer, stating, "These findings suggest that combining [Pluvicto] with standard of care hormonal therapy offers patients more time without disease progression, a safety profile with adverse events that are most often low grade and managed with supportive care, and an encouraging trend in overall survival."

Regulatory Landscape and Market Potential

Pluvicto received FDA approval in March for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in patients who have had an ARPI but not chemotherapy. This approval was based on the phase 3 PSMAfore trial, which showed a 59% reduction in the risk of radiographic progression or death compared to a change in ARPI.

Novartis is now setting its sights on the mHSPC market, which could potentially double Pluvicto's patient population. The company estimates that an approval in mHSPC could push Pluvicto's peak sales above $5 billion. However, some analysts have raised concerns about potential side effects related to continence and sexual function, which may limit uptake among younger mHSPC patients.

In response to these concerns, Novartis CEO Vas Narasimhan has stated that doctors are generally satisfied with Pluvicto's tolerability profile, attributing sexual function issues primarily to the hormonal therapies patients are taking rather than Pluvicto itself.

Safety Profile and Ongoing Research

The PSMAddition trial reported grade 3 or above adverse events in 50.7% of patients in the Pluvicto arm, compared to 43% in the control group. While overall survival data remain immature, Novartis reports an early positive trend, with a preliminary 16% reduction in the risk of death associated with Pluvicto treatment.

The trial is ongoing to gather more mature overall survival data, which will be crucial for regulatory submissions. Novartis plans to submit applications to regulatory authorities by the end of the year, pending final radiographic progression-free survival data and an updated overall survival analysis.