Novartis reveals more data behind Pluvicto expansion bid

Novartis has reported new data to support its drive to expand the label of its radioligand therapy Pluvicto to include hormone-sensitive prostate cancer (HSPC).

The new results come from the PSMAddition trial, first reported at last year's ESMO cancer congress, which formed the basis of Novartis filings to extend the label of Pluvicto (177Lu vipivotide tetraxetan) from its current use in castration-resistant prostate cancer (CRPC).

The new finding is that combining Pluvicto with standard-of-care hormonal therapy for PSMA-positive metastatic HSPC achieved a 58% reduction in progression of PSA – a biomarker for prostate cancer – compared to hormonal therapy alone.

More than 98% of patients in both arms had substantial declines in PSA levels, but more in the Pluvicto group achieved a "deep PSA reduction," reaching levels below 0.2 ng/mL, which would be the clinical benchmark for disease remission.

The improvement compared to standard therapy was seen at 12, 24, and 48 weeks, according to the study investigators, with 87.43% of Pluvicto-treated patients reaching this target at the latter time point compared to 74.9% of the control group.

At ESMO, Novartis reported that the Pluvicto regimen reduced the risk of disease progression or death (radiographic progression-free survival or rPFS) by 28% compared to the control group, prompting Novartis to file for approval of the therapy in this indication in the US, China and Japan, with decisions due in the latter half of this year.

"Our goal in hormone-sensitive prostate cancer is to attack and delay the cancer before it develops resistance," commented Fred Saad of the University of Montreal, who presented the new data at the American Urological Association (AUA) conference over the weekend.

"The deep and durable PSA response observed by combining [Pluvicto] with today's standard of care, together with earlier reported rPFS data, suggest that treatment intensification with radioligand therapy may help patients delay disease progression," he added.

Pluvicto, which was the lead asset in Novartis' $2.1 billion takeover of Endocyte in 2018, was first approved for progressive, PSMA-positive metastatic CRPC in 2022 after initial chemotherapy and had its label extended last year to include the pre-chemo setting based on the PSMAfore trial results.

Sales of the radioligand approached $2 billion last year, but reaching Novartis' target of $5 billion will depend on the drug's label being expanded to include patients with earlier-stage forms of prostate cancer.

Novartis also suffered a setback in that ambitious plan a few weeks ago when it withdrew the therapy for the pre-chemo CRPC indication in the EU in the face of resistance from the EMA.