The designation was supported by findings from the phase 2 Co-PSMA trial, the phase 1/2 COBRA trial, and real-world evidence.
The FDA has granted Breakthrough Therapy designation to the investigational imaging agent 64Cu-SAR-bisPSMA for PET imaging of prostate-specific membrane antigen (PSMA)-positive lesions in men with
Breakthrough Therapy designation is intended to expedite the development and review of investigational drugs for serious conditions when preliminary clinical evidence indicates the potential for substantial improvement over available therapies on clinically significant end points.2 The designation provides the benefits of Fast Track, including more frequent interactions with FDA reviewers, intensive guidance on an efficient development program, and organizational commitment involving senior FDA personnel.
The designation was supported by findings from the phase 2 Co-PSMA trial (NCT06907641), the phase 1/2 COBRA trial (NCT05249127), and real-world evidence, which suggest that the copper-64–labeled agent may improve the detection of recurrent prostate cancer compared with currently available standard-of-care (SOC) PSMA-PET imaging agents.
“Receiving this Breakthrough Therapy designation is one of the most significant milestones in our prostate cancer program to date,” said Alan Taylor, PhD, executive chairperson of Clarity Pharmaceuticals, in a news release from the company.2 “The FDA’s award of the first Breakthrough Therapy designation in the history of PSMA-PET imaging highlights both the unmet need for more accurate detection of recurrent prostate cancer lesions and the significance of the data generated to date, which indicates improved diagnostic performance of 64Cu-SAR-bisPSMA compared to SOC PSMA-PET in patients with BCR of prostate cancer.”
One of the primary studies supporting the designation was Co-PSMA, an investigator-initiated, prospective, head-to-head comparison of 64Cu-SAR-bisPSMA and the approved imaging agent gallium Ga 68 gozetotide (68Ga-PSMA-11) in men with BCR following radical prostatectomy. The study enrolled 50 participants with PSA levels between 0.2 ng/mL and 0.75 ng/mL and a median PSA of 0.43 ng/mL. Participants underwent standard-of-care 68Ga-PSMA-11 PET/CT followed by 64Cu-SAR-bisPSMA PET/CT on the same imaging equipment. The investigational agent was assessed at approximately 1 hour and 24 hours after administration.
The study met its primary end point, demonstrating a higher mean number of lesions detected per patient with 24-hour 64Cu-SAR-bisPSMA imaging compared with 68Ga-PSMA-11 imaging (1.26 vs 0.48; P < .0001). At the patient level, 39 of 50 participants (78%) had positive findings on next-day 64Cu-SAR-bisPSMA PET/CT compared with 18 of 50 (36%) on 68Ga-PSMA-11 PET/CT.
Next-day 68Ga-PSMA-11imaging identified a total of 24 lesions across all participants, whereas 64Cu-SAR-bisPSMA imaging detected 63 lesions. The investigators also reported an increase in the number of lesions identified by 64Cu-SAR-bisPSMA across anatomical regions, including the prostate bed, pelvic and extrapelvic lymph nodes, and bone.
Against a composite reference standard, the reported patient-level true-positive rate was 71% with 64Cu-SAR-bisPSMA compared with 29% with 68Ga-PSMA-11.
At 24 hours, median maximum standardized uptake values (SUVmax) in lesions were 13.6 with 64Cu-SAR-bisPSMA and 5.3 with 68Ga-PSMA-11. Median bladder SUVmax values were 12.0 and 34.5, respectively, suggesting improved tumor-to-background contrast with the investigational agent, according to Clarity. Interreader agreement was also higher with 64Cu-SAR-bisPSMA (Cohen κ = 0.94) than with 68Ga-PSMA-11 (κ = 0.75).
Notably, the imaging findings were associated with changes in planned clinical management. Investigators reported changes to treatment plans in 22 of 50 participants (44%) following 64Cu-SAR-bisPSMA imaging. Common modifications included transitioning patients from observation to active treatment (12 of 22) and changing planned radiation fields (9 of 22). The proportion of patients with an active treatment plan increased from 66% following conventional PSMA-PET imaging to 90% after 64Cu-SAR-bisPSMA imaging.
Clarity is advancing 64Cu-SAR-bisPSMA through 2 phase 3 registrational studies in the US and Australia. AMPLIFY (NCT06970847) is evaluating the agent in patients with BCR following definitive treatment, and CLARIFY (NCT06056830) is evaluating the agent in men with untreated, high-risk prostate cancer who are proceeding to radical prostatectomy and pelvic lymph node dissection.
Clarity reported that both studies have completed recruitment and are in patient follow-up. Topline findings from AMPLIFY and CLARIFY are anticipated in the first half of 2027. The results are intended to support applications to the FDA for approval of the agent in recurrent and newly diagnosed high-risk prostate cancer, respectively.
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REFERENCES
1. First FDA Breakthrough Therapy designation in PSMA PET imaging granted to Cu-64 SAR-bisPSMA in biochemical recurrence of prostate cancer. News release. Clarity Pharmaceuticals. November 12, 2026. Accessed November 12, 2026.
2. Breakthrough Therapy. US Food & Drug Administration. Accessed November 12, 2026.
