FDA Approves First Radiohybrid PSMA-targeted PET Imaging Agent for Prostate Cancer

The FDA has approved flotufolastat F 18 injection (Posluma; formerly ¹⁸F-rhPSMA-7.3) for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA)–positive lesions in men with prostate cancer with suspected metastasis who are eligible for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen level.

The product is an optimized PSMA-targeted molecule that binds to and is internalized by PSMA-expressing cells, including prostate cancer cells, which are known to have PSMA overexpression. It is labeled with the radioisotope fluorine-18 (18F) to allow for PET imaging of the prostate and other areas of the body where prostate cancer could spread. The radioisotope utilizes the high quality of 18F-labeled PSMA PET imaging to effectively identify disease and allow for broad access for patients.

The regulatory decision is supported by findings from two phase 3 trials: LIGHTHOUSE (NCT04186819) and SPOTLIGHT (NCT04186845).

Findings from LIGHTHOUSE indicated that the imaging agent had high specificity when it came to identifying pelvic lymph nodes vs histopathology standard of truth in patients who had PSMA-positive lesions before undergoing radical prostatectomy. Data from SPOTLIGHT indicated that the agent had high detection rates, in the form of positive PET scans, even in those with low PSA levels.

The imaging agent is slated to be commercially available in early June 2023. It will continue to become available on a national scale in the coming months.

“With the FDA approval of Posluma, we realize our goal of providing an important product that will be widely available across the United States to help inform the management and treatment of patients across the prostate cancer care continuum,” David E. Gauden, DPhil., chief executive officer of Blue Earth Diagnostics, stated in a press release. “This event marks a major milestone in the expansion of Blue Earth Diagnostics’ robust prostate cancer portfolio. Posluma was developed to assist physicians in the detection and localization of prostate cancer. It represents a new class of purposely engineered, high-affinity PSMA-targeted radiopharmaceuticals based on novel radiohybrid technology, which may offer diagnostic imaging and therapeutic potential. All of us at Blue Earth Diagnostics want to express our sincere gratitude to the many patients, physicians, clinical trial sites and collaborators who have worked closely with us to progress Posluma.”

SPOTLIGHT

The multicenter, single-arm, phase 3 study examined the safety and diagnostic performance of flotufolastat F 18 injection as a PET imaging product in men who had suspected prostate cancer recurrence based on elevated PSA after previous therapy.²

Data presented at the 2023 American Urological Association Annual Meeting showed that in a subset of patients in the Evaluable PET Scan Population who had received primary treatment and radiation for their disease (n = 76), the overall patient-level detection rate was 99% (n = 75) and proved consistently high across three blinded central readers, with a range of 93% to 99%. Moreover, recurrence by region was 76%, 25%, and 43% for the prostate, pelvic lymph nodes, and extra-pelvic recurrences, respectively.

No serious adverse reactions were reported with the agent on the study. Of the 391 patients who received the PSMA-targeted PET imaging agent, 4.1% experienced at least 1 treatment-emergent adverse effect thought to potentially be related or to be related to the agent. The most common toxicities included hypertension (1.8%), diarrhea (1.0%), injection site reaction (0.5%), and headache (0.5%).

LIGHTHOUSE

The prospective, multicenter, single-arm, phase 3 study set out to examine the safety and diagnostic performance of flotufolastat F 18 injection in patients with newly diagnosed prostate cancer.³

Findings presented at the 2023 Genitourinary Cancers Symposium included an evaluation of the verified detection rate of distant metastatic lesions by imaging. This rate was defined as the proportion of patients with M1 lesions detected via blinded image evaluation and also confirmed as true positive by biopsy or follow-up conventional imaging.

Data, which were based on individual read results from three blinded independent PET readers, showed that of the 355 men with treatment-naïve, unfavorable intermediate to very-high-risk prostate cancer scheduled to receive radical prostatectomy and PLND, 16% to 28% had M1 lesions across the readers. Ten percent to 15% had verified M1 lesions. When examined by region, verified M1 lesions were noted to be most prevalent in the bone, ranging from 6.0% to 11% across the readers.

In a subgroup with negative baseline conventional imaging (n = 314), similar data were observed. In this group, the verified detection rate ranged from 9% to 13% across the readers and bone proved to be the highest regional rate, ranging from 5% to 9%.

References

1. US FDA approves Blue Earth Diagnostics' Posluma (flotufolastat F 18 injection, first radiohybrid PSMA-targeted PET imaging agent for prostate cancer. News release. Blue Earth Diagnostics. May 30, 2023. Accessed May 30, 2023. https://4078578.fs1.hubspotusercontent-na1.net/hubfs/4078578/POSLUMA%20approval%20press%20release%20FINAL%20for%20May%2030%202023.pdf
2. Blue Earth Diagnostics announces additional results from phase 3 SPOTLIGHT trial of investigational PET imaging agent ¹⁸F-rhPSMA-7.3 in biochemical recurrence of prostate cancer. News release. Blue Earth Diagnostics. April 29, 2023. Accessed May 30, 2023. https://4078578.fs1.hubspotusercontent-na1.net/hubfs/4078578/AUA%202023%20SPOTLIGHT%20subgroup%20results%20Final%20for%20April%2029%202023-2.pdf
3. Blue Earth Diagnostics announces additional results from phase 3 LIGHTHOUSE trial of investigational PET imaging agent ¹⁸F-rhPSMA-7.3 in newly diagnosed prostate cancer. News release. Blue Earth Diagnostics. February 16, 2023. Accessed May 30, 2023. https://4078578.fs1.hubspotusercontent-na1.net/hubfs/4078578/Additional%20LIGHTHOUSE%20results%20for%20ASCO%20GU%202023%20February%2016%202023.pdf