Novartis' Pluvicto Shows Promise in Hormone-Sensitive Prostate Cancer, Paving Way for FDA Application

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 results, presented at the 2025 European Society for Medical Oncology (ESMO) congress in Berlin, mark a potential expansion of Pluvicto's indications and patient population.

Pluvicto's Efficacy in mHSPC

The PSMAddition trial evaluated Pluvicto in combination with standard of care treatment for patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC). Results showed that Pluvicto plus standard of care – which includes androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) such as Pfizer and Astellas' Xtandi – reduced the risk of radiographic progression or death by 28% compared to standard of care alone.

While Novartis hails this improvement as statistically significant and clinically meaningful, it's worth noting that the magnitude of benefit is not as striking as previously seen with Pluvicto in other settings or with other treatments in mHSPC. For context, Pluvicto demonstrated a 59% reduction in the risk of radiographic progression or death in metastatic castration-resistant prostate cancer (mCRPC) in the PSMAfore trial, which led to its FDA approval for that indication in March.

Regulatory Plans and Market Potential

Based on these results, Novartis plans to submit applications to regulatory authorities, including the FDA, by the end of the year. The company is awaiting final radiographic progression-free survival data and an updated overall survival analysis before proceeding with submissions.

An approval in mHSPC would significantly expand Pluvicto's market potential. Novartis estimates that this new indication would double the number of patients eligible for the treatment. The company projects that Pluvicto could reach peak sales above $5 billion with this expanded indication.

However, some analysts have raised concerns about potential limitations to Pluvicto's uptake in the mHSPC population. A Goldman Sachs analyst suggested that side effects related to continence and sexual function might deter younger mHSPC patients from choosing the treatment. Novartis CEO Vas Narasimhan has countered these concerns, stating that doctors are generally satisfied with Pluvicto's tolerability profile and that sexual function issues are primarily attributed to the hormonal therapies patients are already taking.

Safety Profile and Expert Opinion

In the PSMAddition trial, grade 3 or above adverse events were reported in 50.7% of patients in the Pluvicto arm, compared to 43% in the control group. Despite this slightly higher incidence of severe adverse events, experts remain optimistic about Pluvicto's potential in earlier-stage prostate cancer treatment.

Dr. Scott Tagawa from Weill Cornell Medicine emphasized the importance of choosing the most efficacious treatment early in metastatic prostate cancer. He stated, "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."

As the pharmaceutical industry continues to advance treatments for prostate cancer, Pluvicto's potential expansion into the mHSPC setting represents a significant development that could reshape treatment paradigms and improve outcomes for patients with this challenging disease.