Background and objectives:
Teverelix drug product (DP) is a
gonadotropin-releasing hormone antagonist in development for the treatment of patients with
prostate cancer in whom
androgen deprivation
therapy is indicated. The aim of this paper is to present the results of five Phase 2 studies that assessed the pharmacokinetics, pharmacodynamics, efficacy and safety of different loading dose regimens of
teverelix DP. Methods: Five single-arm, uncontrolled clinical trials were conducted in patients with advanced
prostate cancer. The five different loading dose regimens of
teverelix DP tested were (a) a single 90 mg subcutaneous (SC) injection of
teverelix DP given on 3 consecutive days (Days 0, 1 and 2); (b) a single 90 mg intramuscular (IM) injection of
teverelix DP given 7 days apart (Days 0 and 7); (c) a single 120 mg SC injection of
teverelix DP given on 2 consecutive days (Days 0 and 1); (d) 2 × 60 mg SC
injections of
teverelix DP given on 3 consecutive days (Days 0, 1 and 2), and (e) 2 × 90 mg SC
injections of
teverelix DP given on 3 consecutive days (Days 0, 1 and 2). The primary efficacy parameter was the duration of action of an initial loading dose regimen in terms of suppression of
testosterone to below the
castration level (0.5 ng/mL). Results: Eighty-two patients were treated with
teverelix DP. Two regimens (90 mg and 180 mg SC on 3 consecutive days) had a mean duration of
castration of 55.32 days and 68.95 days with >90% of patients having
testosterone levels < 0.5 ng/mL at Day 28. The mean onset of
castration for the SC regimens ranged from 1.10 to 1.77 days, while it was slower (2.4 days) with IM administration. The most common adverse event (AE) was
injection site reaction. No AEs of severe intensity were reported. Conclusions:
Teverelix DP is safe and well tolerated. Castrate levels of
testosterone can be rapidly achieved following the
subcutaneous injection of
teverelix DP on 3 consecutive days. Streamlining of the administration of the loading dose and identifying a suitable maintenance dose will be investigated in future trials.