Novartis to File for Pluvicto Label Expansion After Promising Phase III Data

Novartis_iStock, Michael Derrer Fuchs

Pictured: Novartis office in Basel, Switzerland/iStock, Michael Derrer Fuchs

Novartis on Thursday announced that it plans to file for a label expansion for its radioligand therapy Pluvicto (lutetium-177 vipivotide tetraxetan) later this year, proposing to use the prostate cancer treatment in patients who have not yet undergone chemotherapy.

The announcement follows additional data from the Phase III PSMAfore study, demonstrating overall survival (OS) data that leaned in favor of Pluvicto.

Novartis did not provide specific data in its brief announcement, only revealing that “a pre-planned analysis at approximately 75% information fraction demonstrates an OS hazard ratio less than 1.0” in PSMAfore’s intent-to-treat population, without adjusting for cross-over.

Pluvicto’s safety profile in the interim analysis remains consistent with what had been previously disclosed in prior readouts, according to the announcement. Novartis will present full findings from PSMAfore at an upcoming medical meeting.

Designed to be intravenously administered, Pluvicto is a targeted radioligand therapeutic that works by seeking out the PSMA protein, which is typically found on prostate cancer cells. According to its label, Pluvicto’s active moiety is the radionucleotide lutetium-177, the beta-emissions from which damage the PSMA-positive cancer cells, induce DNA damage and trigger cell death.

The FDA signed off on Pluvicto in March 2022, allowing its use in adult patients with metastatic castration-resistant prostate cancer who are positive for the PSMA protein. Currently, Pluvicto can only be administered to those who have been exposed to an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy.

Using data from the PSMAfore study, Novartis is seeking to push Pluvicto up into an earlier line of treatment, before taxane therapies.

However, in October 2023, the pharma reported that the trial’s OS data were “confounded” by a strong cross-over effect—84% of patients who discontinued ARPI treatment due to radiographic progression transitioned to the Pluvicto arm. Adjusting for cross-overs pointed to a non-significant advantage for Pluvicto, though placebo was better in the unadjusted analysis.

Still, PSMAfore met its primary endpoint. The risk of radiographic progression-free survival was 59% lower in the Pluvicto group, compared with simply switching to another ARPI therapy. The radioligand therapy also improved patients’ quality of life, delayed the worsening of their pain and lowered prostate-specific antigen levels.

If its label expansion is approved, earlier Pluvicto treatment may help patients avoid the toxic side effects of chemotherapy—and may open a larger market for the targeted treatment.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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