Production of 2 FDA-Approved Radioligand Agents for Prostate Cancer Temporarily Halts

Production of lutetium Lu 177 vipivotide tetraxetan (Pluvicto; formerly 177Lu-PSMA-617) and Luthathera (lutetium-177 dotatate) have been temporarily suspended due to potential quality issues identified in their manufacturing processes, according to Novartis.¹

The action has been taken out of an abundance of caution and Novartis aims to conduct a thorough review of the situation. The company expects both the issue to be resolved and supply to resume within the next 6 weeks.

Further, the company has placed a temporary hold on screening and enrollment for both 177Lu-PSMA-617 clinical trials globally, and Lutathera clinical trials across the US and Canada.

“Quality and patient safety are our top priorities. There is currently no indication of any risk to patients from doses previously produced at these sites. Novartis has notified treatment sites to closely monitor patients who have recently been injected and asked them to report any adverse events to Novartis patient safety,” stated the press release.

The FDA previously granted approval to Pluvicto victo in March 2022, for the treatment of adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer that has spread to other parts of the body and who have previously received other anticancer therapies, such as androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.

Pluvicto is the first radioactive diagnostic agent to receive regulatory approval for patient selection in the use of a radioligand therapeutic agent.

Findings from the phase 3 VISION trial (NCT03511664) supported the decision as data demonstrated a statistically significant reduction in risk of death (38% reduction) for patients with PSMA-positive mCRPC who previously received AR pathway inhibition and taxane-based chemotherapy and received Pluvicto plus standard of care (SOC).

The median overall survival (OS) reported in the investigative arm was 15.3 months vs 11.3 months in the control arm (HR, 0.62; 95% CI, 0.52-0.74; P < .001). About one-third of patients with evaluable disease at baseline experienced an overall response to lutetium Lu 177 vipivotide tetraxetan plus SOC vs 2% in the SOC-alone arm. Radioligand therapy also showed a significant reduction in risk of radiographic disease progression or death vs SOC alone, yet interpretation of the magnitude of radiographic progression-free survival (rPFS) effect was limited due to there being a high degree of censoring from early drop out in the control arm.

Patients with CRPC who had at least 1 metastatic lesion at baseline computed tomography, magnetic resonance imaging, or bone-scan imaging were enrolled within the VISION trial. Patients must have progressed following prior treatment with 1 or more approved AR pathway inhibitor and with 1 or 2 taxane regimens and needed to have at least 1 PSMA-positive metastatic lesion. Other requirements included having an ECOG performance status ranging from 0 to 2, a life expectancy of at least 6 months, and acceptable organ and bone marrow function.

Those enrolled in the study were randomized 2:1 to receive either Lu 177 vipivotide tetraxetan at 7.4 GBq (+/- 10%) intravenously every 6 weeks for up to 6 cycles with SOC or the best SOC alone. Participants were administered standard treatment, with or without the radioligand therapy, until disease progression, intolerable toxicity, lack of clinical benefit, or a prohibited treatment was determined to be necessary.

A total of 831 patients were included and assessed for the coprimary endpoints of OS and rPFS. The secondary end point of the study was the number of patients with treatment-emergent adverse events (TEAEs).2

Findings revealed that at a median follow-up of 20.9 months, the median OS observed in the Lu 177 vipivotide tetraxetan plus SOC arm was 15.3 months vs with 11.3 months in the SOC-alone arm (HR, 0.61; 95% CI, 0.52-0.74; P <.0001). The median rPFS observed with Lu 177 vipivotide tetraxetan plus SOC was 8.7 months compared to 3.4 months with SOC alone (HR, 0.40; 99.2% CI, 0.29-0.57; P <.001). The results for all the secondary efficacy endpoints favored the Lu 177 vipivotide tetraxetan combination as well.

In regard to safety, Lu 177 vipivotide tetraxetan appeared consistent with its profile in earlier analyses. Any-grade AEs were reported as being seen in 98.1% of patients in the combination arm compared with 82.9% in the SOC arm. The most common AEs observed with the experimental combination included fatigue (43.1%), dry mouth (38.8%), and nausea (35.3%). Fatigue and nausea were also commonly observed in the SOC arm at 22.9% and 16.6%, respectively.

References

1. Novartis provides updates on production of radioligand therapy medicines. News Release. Novartis; May 5, 2022. Accessed May 9, 2022. https://bit.ly/3P7DfrJ

2.Novartis Pluvicto™ approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer. News Release. Novartis; March 23, 2022. Accessed May 9, 2022. https://bit.ly/38dfeyI