Swissmedic Accepts Marketing Authorization Application for Piflufolastat (18F) for Prostate Cancer

The Swiss Agency for Therapeutic Products (Swissmedic) has accepted for evaluation a marketing authorization application (MAA) seeking the approval of the (18F)–prostate-specific membrane antigen (PSMA) PET tracer piflufolastat (18F) (Pylclari; formerly (18F) DCFPyL) for therapeutic use in adult patients with prostate cancer. The MAA was submitted on January 31, 2024, by the Swiss distributor b.e.imaging AG.¹

Piflufolastat (18F) is indicated to detect PSMA-positive lesions using PET in adult patients with prostate cancer in the following clinical settings:

• To localize suspected prostate cancer recurrence based on increasing serum prostate-specific antigen (PSA) levels after primary curative-intent treatment
• To conduct primary staging of patients with high-risk prostate cancer prior to initial curative-intent therapy

The submission of the MAA was supported by the MAA for (18F)-DCFPyL, which was submitted to the European Medicines Agency in July 2022. Subsequent marketing authorization for (18F)-DCFPyL was granted by the European Commission in July 2023.

“b.e.imaging is proud of the submission of the MAA for [piflufolastat (18F)] to Swissmedic ahead of schedule,” Michel Wuillemin, PhD, MS, head of Radiopharmaceuticals at b.e.imaging, stated in a news release. “We are fully dedicated to improving the situation of prostate cancer patients in Switzerland.”

“The acceptance of the marketing authorization application by Swissmedic for [piflufolastat (18F)] is another important milestone for [patients with] prostate cancer Switzerland,” Benoit Woessmer, the chief executive officer of PET Europe at Curium, added in the news release. 'We look forward to providing an improved choice of tools available to physicians for the diagnosis of [patients with] prostate cancer. Importantly, when in full production, [piflufolastat (18F)] is expected to be the most widely available 18F-PSMA tracer in Europe.”

Previously, piflufolastat F 18 injection (18F)-DCFPyL (Pylarify) was approved by the FDA in May 2021 to identify suspected prostate cancer metastases or recurrence.² The regulatory decision was supported by findings from the phase 2/3 OSPREY (NCT02981368) and phase 3 CONDOR (NCT03739684) trials.

In cohort A of OSPREY (n = 252), (18F)-DCFPyL showed improved specificity and positive predictive value (PPV) vs conventional imaging in patients at risk for metastatic prostate cancer prior to initial therapy.³ The median PPV with (18F)-DCFPyL was 86.7% (95% CI, 69.7%-95.3%), and the median specificity with the agent was 97.9% (95% CI, 94.5%-99.4%). In cohort B (n = 93), the median PPV with (18F)-DCFPyL was 81.9% (95% CI, 73.7%-90.2%), and the median sensitivity with (18F)-DCFPyL was 95.8% (87.8%-99.0%) in patients with suspected recurrent or metastatic prostate cancer on conventional imaging.

In CONDOR, which enrolled patients with biochemical recurrent prostate cancer and noninformative baseline imaging (n = 208), (18F)-DCFPyL generated high rates of correct metastatic prostate cancer localization and detection, including in patients with low PSA values, defined as those with a median PSA of 0.8 ng/mL.⁴ The correct localization rate with (18F)-DCFPyL was 84.8% to 87.0% (lower bound of 95% CI, 77.8%-80.4%).

(18F)-DCFPyL was well tolerated in both OSPREY and CONDOR, in which a combined total of 593 patients with varying states of prostate cancer received a single dose of the agent. Adverse effects, including dysgeusia, fatigue, and headache, were reported in 2% or fewer of patients in the trials. Moreover, 1 patient with a history of allergic reaction experienced delayed hypersensitivity reaction.

The recommended dose of (18F)-DCFPyL in the United States is 333 MBq (9 mCi). The acceptable dosing range is 296 MBq (8 mCi) to 370 MBq (10 mCi), and the agent is administered as a bolus intravenous injection.

References

1. Curium announces submission of the marketing authorization application for PYLCLARI, an innovative (18F)-PSMA PET tracer indicated in adults with prostate cancer to Swissmedic. News Release. Curium. February 21, 2024. Accessed February 22, 2024. https://www.curiumpharma.com/2024/02/21/marketing-authorization-pylclari-swissmedic/
2. Lantheus receives U.S. FDA approval of PYLARIFY (Piflufolastat F18) injection, the first and only commercially available PSMA PET imaging agent for prostate cancer. News Release. Lantheus Holdings, Inc. May 27, 2021. Accessed February 22, 2024. https://investor.lantheus.com/news-releases/news-release-details/lantheus-receives-us-fda-approval-pylarifyr-piflufolastat-f-18
3. Pienta KJ, Gorin MA, Rowe SP, et al. A phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/CT with 18F-DCFPyL in prostate cancer patients (OSPREY). J Urol. 2021;206(1):52-61. doi:10.1097/JU.0000000000001698
4. Morris MJ, Rowe SP, Gorin MA, et al. Diagnostic performance of 18F-DCFPyL-PET/CT in men with biochemically recurrent prostate cancer: results from the CONDOR phase III, multicenter study. Clin Cancer Res. 2021;27(13):3674-3682. doi:10.1158/1078-0432.CCR-20-4573