Regulatory Decision Summary for Camcevi

The Sponsor conducted a multicenter, multinational, open label, single arm, phase III study (FP01-13-001) to evaluate the efficacy, safety and pharmacokinetic behavior of Camcevi(leuprolide mesylate, 6 month depot) in adult patients with histologically confirmed advanced prostate cancer and morning serum testosterone levels >150 ng/dL. Patients were scheduled to receive a total of two doses given 6 months apart.

The primary efficacy endpoints were testosterone suppression (castrate levels < 50 ng/dL) by day 28 and maintenance of testosterone suppression from day 28 though day 336 in ≥ 90% of patients. Key secondary endpoints included post suppression excursions (> 50 ng/dL), and testosterone suppression below 20 ng/dL. A total of 137 subjects were enrolled and received at least one dose of the study drug (intent-to-treat [ITT] population), and 124 subjects completed the study with two doses of Camcevi and without major protocol violations affecting the primary efficacy endpoint (per-protocol population [PP]).

Treatment with Camcevi led to significant suppression of testosterone levels below the castrate levels (< 50 ng/dL) in 99% of patients by day 28 in the ITT population. Testosterone suppression was maintained in 97% of patients from day 28 through day 336 in the ITT population. Similar results were observed in the PP population. The primary endpoint was supported by the low frequency of patients (~3%), that suffered post-suppression excursions and by the high percentage, 85%, of patients in the ITT population that maintained a deeper testosterone suppression characterized by serum levels of less than 20 ng/dL. 

The safety profile of Camcevi was characterized in the pivotal study involving all 137 advanced prostate cancer patients. The significant safety risks are cardiovascular (myocardial infarctions, QTc prolongation), endocrine (pituitary apoplexy, bone pain, hyperglycemia, hypogonadism), hematologic (anemia), neurologic (convulsions) tumour flare (ureteric obstruction and spinal cord compression), reproductive, and respiratory (pneumonitis). These risks are consistent with the known safety profile of other authorized leuprolide based products such as leuprolide acetate. Notably, a safety extension study of the pivotal trial that examined the safety of two additional doses of Camcevi, did not identify new risks that would impact the safety or tolerability of Camcevi. All of the significant safety risks are now clearly highlighted in the Adverse Reactions table, the Serious Warnings and Precautions Box and Warnings and Precautions section of the Product Monograph (PM). Moreover, these risks are generally manageable with dose discontinuation and/or standard medical practice. These mitigation strategies are clearly outlined in the PM.

The clinical pharmacological and non-clinical data supported the intended use of Camcevi in the target population. Key clinical pharmacology and non-clinical findings, relevant risks and uncertainties were properly addressed in the final PM.

This submission was considered to comply with the Quality data requirements of Section C.08.002 of the Food and Drug Regulations.

The labelling documents conform to the necessary regulatory requirements and are consistent with the labelling guidance documents.

The Risk Management Plan was considered acceptable. 

In summary, the pivotal study met its primary endpoint demonstrating significant testosterone suppression in greater than 90% of the patient population. The efficacy was coupled with a tolerable and manageable safety profile that was also consistent with other authorized leuprolide products. As such, the benefit-risk profile is considered positive under the proposed conditions of use.