EMA Committee Recommends Piflufolastat 18F PSMA PET Imaging Agent for Prostate Cancer

Sakir Mutevelic, MD, MS

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of piflufolastat ¹⁸F (Pylclari; [¹⁸F]-DCFPyL) for the primary staging of patients with high-risk prostate cancer before initial curative treatment and to localize recurrence of the disease in those with a suspected recurrence based on rising serum prostate-specific antigen (PSA) levels following initial treatment with curative intent.¹

The marketing authorization application (MAA) for the product, submitted in June 2022,² was based on data from the phase 3 PYTHON trial (NCT04734184) which was done in Europe and compared piflufolastat 18F with the established standard, (¹⁸F)-fluorocholine, in patients with biochemical recurrence following initial definitive treatment with prostatectomy, external beam radiotherapy, or brachytherapy for prostate adenocarcinoma.³ The trial was reported to meet its primary end point, which was per-patient detection rate.²

The application was also based on findings from the phase 3 OSPREY (NCT02981368) and CONDOR (NCT03739684) trials, both conducted in the United States.¹

The positive opinion will be referred to the European Commission who will reach a decision on the MAA within about 2 months.

“We are extremely pleased with the CHMP positive opinion and recommendation to grant a marketing authorization in Europe for Pylclari, a diagnostic imaging medicine for the detection of prostate-specific membrane antigen–positive lesions with positron emission tomography in adults with prostate cancer…,” Sakir Mutevelic, MD, MSc, chief medical officer at Curium, stated in a press release.

In May 2021, the FDA approved piflufolastat ¹⁸F(Pylarify) injection to identify suspected metastasis or recurrence of prostate cancer based on data from OSPREY and CONDOR.⁴

Investigators on the CONDOR study set out to examine the diagnostic performance and safety of the imaging agent in patients with suspected recurrence of prostate cancer who have negative or equivocal results by conventional imaging.⁵ Piflufolastat ¹⁸F was found to have high correct localization and detection rates in patients with biochemical recurrent prostate cancer and non-informative imaging at baseline, including in those with low PSA defined as a median of 0.8 ng/mL.⁴

The diagnostic performance of the imaging product was also examined in men with National Comprehensive Cancer Network high-risk prostate cancer slated to undergo radical prostatectomy (cohort A) and those with radiologically suspected recurrent or metastatic disease (cohort B) as part of the OSPREY trial.⁶ Here, the agent was given at a single dose of 9 mCi.

Findings from cohort A revealed an improvement in specificity and positive predictive value of piflufolastat ¹⁸F compared with conventional imaging.⁴ Updated results from both cohorts indicated that uptake of piflufolastat ¹⁸F was significantly higher in biopsy and lesions and increased with baseline PSA.⁷

“We are very excited to bring Pylclari to the market and contribute to improving the set of diagnostic tools available to better diagnose and monitor prostate cancer,” Benoit Woessmer, PET Europe chief executive officer at Curium, added in the press release.¹ “PSMA PET with Pylarify is the standard of care in the United States. We are looking forward to answering the high expectations of the nuclear medicine community when it comes to having the right tool reliability available to address the fast-growing pathology.”

References

1. Curium receives positive CHMP opinion of Pylclari for primary staging of patients with high-risk PCa prior to initial curative therapy and to localize recurrence of PCa in patients with suspected recurrence based on increasing serum prostate-specific antigen (PSA) levels after primary treatment with curative intent. News release. Curium. May 26, 2023. Accessed June 1, 2023. https://www.curiumpharma.com/2023/05/26/curium-receives-positive-chmp-opinion/
2. Curium announces the submission of its marketing authorization application for [18F]-DCFPyL to the European Medicines Agency. News release. Curium. June 27, 2022. Accessed June 1, 2023. https://www.curiumpharma.com/2022/06/27/submission-marketing-authorization-application-for-18f-dcfpyl-to-european-medicines-agency/
3. A prospective study on 18F-DCFPyL PET/CT imaging in biochemical recurrence of prostate cancer (Python). ClinicalTrials.gov. Updated February 2, 2021. Accessed June 1, 2023. https://clinicaltrials.gov/ct2/show/NCT04734184
4. Lantheus receives US FDA approval of Pylarify (piflufolastat F 18) injection, the first and only commercially available PSMA PET imaging agent for prostate cancer. News release. Lantheus Holdings, Inc. May 27, 2021. Accessed June 1, 2023. https://investor.lantheus.com/news-releases/news-release-details/lantheus-receives-us-fda-approval-pylarifyr-piflufolastat-f-18
5. Study of 18F-DCFPyL PET/CT imaging in patients with suspected recurrence of prostate cancer (CONDOR). ClinicalTrials.gov. Updated June 14, 2021. Accessed June 1, 2023. https://clinicaltrials.gov/ct2/show/NCT03739684
6. Gorin MA, Rowe SP, Pienta KJ, et al. Piflufolastat F 18-PET/CT in prostate cancer patients: an analysis of OSPREY (cohorts A and B) standardized uptake value (SUV) results stratified by PSA and Gleason score. J Clin Oncol. 2022;40(suppl 6):035. doi:10.1200/JCO.2022.40.6_suppl.035