Novartis withdraws EMA application to expand Pluvicto into earlier prostate cancer setting

Novartis Europharm Limited withdrew its application to vary the marketing authorization for Pluvicto (lutetium (177Lu) vipivotide tetraxetan) with the European Medicines Agency (EMA), the agency confirmed in April 2026. The withdrawal, filed on 23 March 2026, concerned a proposed label extension into an earlier treatment setting for PSMA-positive metastatic castration-resistant prostate cancer — specifically, patients with no or mild symptoms whose disease had progressed on an androgen receptor pathway inhibitor (ARPI) and who were not yet eligible for taxane-based chemotherapy.

The variation application sought to extend Pluvicto's use beyond its current EU authorization, which covers adults with progressive PSMA-positive mCRPC previously treated with both an ARPI and a taxane. The withdrawn filing would have repositioned the radioligand therapy earlier in the treatment sequence, before chemotherapy becomes indicated.

The company submitted data from a study in adults with PSMA-positive, progressive mCRPC who had received prior hormone-blocking therapy and remained chemotherapy-naive. The trial compared Pluvicto against an alternative hormone-blocking medicine, with radiographic progression-free survival as the primary endpoint. Overall survival was also assessed.

The agency's review identified unresolved concerns before the withdrawal was formalized. Although the study demonstrated an increase in time before radiographic progression compared with the comparator, the EMA's provisional assessment questioned whether that delay represented a meaningful clinical benefit. Central to that concern was the nature of the comparator: the EMA indicated that the hormone-blocking treatment used as a control was not considered adequate therapy for patients at that stage of disease, which complicated interpretation of the progression-free survival advantage. The agency also noted that Pluvicto showed no overall survival benefit relative to the comparator arm.

In its withdrawal notification, Novartis stated that feedback from the Committee for Medicinal Products for Human Use indicated the committee would not be able to conclude, on the basis of the data provided, that the benefits of Pluvicto outweighed its risks in the applied indication.

Pluvicto was first authorized in the EU in December 2022 for its current indication and is administered by intravenous injection or infusion once every six weeks for up to six doses, alongside androgen deprivation therapy. Its mechanism centres on the PSMA-targeting ligand vipivotide tetraxetan, which delivers localised beta-particle radiation from lutetium-177 to PSMA-expressing tumour cells. The drug remains authorised and available in the EU for its existing indication following the withdrawal of the variation request.

The pre-chemotherapy mCRPC setting that Novartis sought to enter is one of the more actively contested areas in prostate cancer drug development. PSMA-directed approaches and androgen receptor pathway agents have both generated clinical interest in this population, and the question of sequencing — which agents to use, and when — remains an area of active investigation. The withdrawn application adds to a body of experience suggesting that demonstrating benefit in earlier, less symptomatic disease settings can present distinct evidentiary demands compared with later-line populations where treatment options are more limited and the clinical need more acute.

For Novartis, the withdrawal does not affect Pluvicto's commercial or regulatory standing in its approved indication, but it closes, at least for now, a pathway that would have broadened the drug's eligible patient population in Europe. Whether the company will pursue a revised submission supported by different data, an alternative comparator design, or additional follow-up from the existing study was not indicated in the EMA's published account of the withdrawal.

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