Avorelin: Is a 12-monthIy LHRH depot implant on the horizon?

Introduction: We report an open-label, dose-interval determining, multicentre phase II study to investigate Avorelin, a new synthetic decapeptide analogue of LHRH for men with prostate cancer. Avorelin is an acetate salt of [(2-Me-D-Trp)⁶, (Pro-NHEt)⁹, (DesGly)¹⁰]-LHRH, dispersed in a slowly degrading high molecular weight polylactic-co-glycolic acid (PLGA) polymer, delivered as a depot preparation. Patients and methods: Sixty men with histologically confirmed metastatic or non-metastatic prostate cancer were randomized to either 10 mg (31) or 15 mg (29) subcutaneous implants. Serum levels of testosterone, LH, FSH and Avorelin were estimated until two consecutive testosterone values one week apart were > 2.0 nmol/L. Antiandrogen therapy was not used to cover tumour flare, but was used to control intolerable hot flushes. Results: Medical castration was achieved by 28 days in all patients. Testosterone suppression to castrate levels has been maintained in the 38 men who have reached at least 6 months (24 weeks) and in three men after > 12 months. The median duration of implant to the first elevation of testosterone level > 2.0 nmol/L was slightly more than 9 months (37 weeks) in the 10 mg group, and 8.8 months (35 weeks) in the 15 mg group. Implant exhaustion was detected to date in 20 of 60 men after 30-56 weeks (14 with 10 mg and six with 15 mg implants). After 3 months, the median baseline PSA levels were reduced by 93% and 92% (10 mg and 15 mg implants, respectively), with no further significant decrease in PSA from week 12 onwards. Avorelin was well tolerated. Conclusions: This study presents the preliminary results of a new long-acting LHRH analogue. Avorelin, with an effective implant duration of 9-12 months.