Clarity Pharmaceuticals has achieved significant milestones in its prostate cancer program, securing Fast Track Designations (FTD) from the U.S. Food and Drug Administration (FDA) for both its diagnostic and therapeutic agents. 64Cu-SAR-bisPSMA has received FTD for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA) positive prostate cancer lesions in patients with biochemical recurrence (BCR) of prostate cancer following definitive therapy. Additionally, 67Cu-SAR-bisPSMA has been granted FTD for the treatment of adult patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with androgen receptor pathway inhibition (ARPI).
These designations are designed to expedite the development and regulatory review of novel drugs and diagnostics addressing serious conditions with unmet medical needs. The FTD allows Clarity Pharmaceuticals to benefit from a faster review process, more frequent communication with the FDA, and the ability to submit completed sections of its application as they become available.
64Cu-SAR-bisPSMA: Improved Diagnostics for Biochemical Recurrence
The FDA's decision to grant FTD for 64Cu-SAR-bisPSMA was supported by data from the Phase I/II COBRA trial (NCT05249127), which evaluated the safety and diagnostic performance of the agent in detecting prostate cancer in patients with BCR who had negative or equivocal standard of care (SOC) scans at study entry. The trial demonstrated that next-day PET imaging with 64Cu-SAR-bisPSMA showed localized disease in up to 80% of participants and detected lesions as small as 2 mm. This compares favorably against current SOC PSMA PET agents, with which the detection of lesions smaller than 5 mm is challenging.
According to Clarity, findings from the COBRA study informed planning for the ongoing Phase III AMPLIFY trial, a non-randomized, single-arm, open-label, multi-center trial that will further evaluate the ability of 64Cu-SAR-bisPSMA PET/CT to detect biochemical recurrence of prostate cancer in approximately 220 participants with rising or detectable prostate-specific antigen (PSA) levels following initial definitive treatment for prostate cancer.
67Cu-SAR-bisPSMA: Advancing Treatment for mCRPC
The FDA also granted FTD to 67Cu-SAR-bisPSMA for the treatment of adult patients with PSMA-positive mCRPC who have been previously treated with ARPI. This decision was supported by preliminary data from the Phase I/IIa SECuRE trial (NCT04868604), which is investigating the safety and efficacy of the agent as a treatment for patients with mCRPC. Preliminary data from the SECuRE study showed that 73% of patients across all cohorts experienced reductions in PSA levels. PSA reductions of greater than 50% were seen in 45% of all trial participants, despite the overwhelming majority of participants only receiving a single dose of 67Cu-SAR-bisPSMA (4, 8 or 12 GBq) in the trial.
In the SECuRE trial, the largest drop in prostate-specific antigen (PSA) in cohort 4 to date is a decline of 98% (from a baseline of 157.4 ng/mL). This participant, who had failed multiple lines of therapy prior to receiving 67Cu-SAR-bisPSMA (androgen deprivation therapy [ADT], ARPI and an investigational agent), has already had a radiographic partial response based on the investigator’s assessment of Response Evaluation Criteria in Solid Tumours v1.1 (RECIST) criteria. Preliminary analysis showed a reduction of 60.6% in tumour volume evaluated by PSMA positron emission tomography [PET] imaging with 64Cu-SAR-bisPSMA.
Clarity's Perspective
Clarity's Executive Chairperson, Dr Alan Taylor, commented, "Receiving 3 FTDs for the one molecule, SAR-bisPSMA, within the last 6 months is an incredible achievement for Clarity, highlighting how impressive our science and development are, the significance of the diagnostic and therapeutic data so far, and the high unmet need for better therapies and diagnostics in prostate cancer."
About SAR-bisPSMA
SAR-bisPSMA derives its name from the word "bis", which reflects a novel approach of connecting two PSMA-targeting agents to Clarity's proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-bisPSMA is a Targeted Copper Theranostic (TCT) that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.
Both 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA are unregistered products, and their safety and efficacy have not been assessed by health authorities such as the U.S. FDA or the Therapeutic Goods Administration (TGA). There is no guarantee that these products will become commercially available.
