Corifollitropin Alfa Combined With Human Chorionic Gonadotropin in Adolescent Boys With Hypogonadotropic Hypogonadism

Abstract

Background We examined the efficacy and safety of corifollitropin alfa (CFA) combined with human chorionic gonadotropin (hCG) for the induction of testicular growth and pubertal development in adolescent boys with hypogonadotropic hypogonadism (HH). Methods This was a 64-week, multi-center, open-label, single-group study of CFA in adolescent males, 14 to <18 years of age, with HH. Seventeen participants initiated a 12-week priming period with CFA (100 μg if weight ≤60 kg, or 150 μg if weight >60 kg) given subcutaneously (SC) once every two weeks (q2wk), after which they entered a 52-week combined treatment period with CFA, q2wk, and SC hCG, twice-weekly (hCG dose adjusted between 500 IU and 5,000 IU to keep total testosterone and estradiol levels within protocol-specified ranges). The primary efficacy endpoint was change from baseline in testicular volume (TV), measured as the sum of volumes of left and right testes by ultrasound. Results After 64 weeks of therapy with CFA/CFA combined with hCG, geometric mean fold increase from baseline in TV was 9.43 [95% CI: 7.44, 11.97] (arithmetic mean of change from baseline at Week 64, 13.0 mL). Hormonal, Tanner stage, and growth velocity changes were consistent with initiation and progression of puberty. Treatment was generally well tolerated. No participant developed anti-CFA antibodies. Conclusions Treatment of adolescent males with HH with CFA alone for 12 weeks followed by CFA combined with hCG for 52 weeks induced testicular growth accompanied by pubertal progression, increased testosterone, and a pubertal growth spurt. (EudraCT: 2015-001878-18)

Spermatogenesis induction audit over a 5-year period at a UK male fertility centre

“…5 Exogenous testosterone treatment in young males with hypogonadism can promote premature maturation of Sertoli cells, that could negatively impact future fertility. 6,7 Early gonadotrophin therapy might be advocated in preference to testosterone replacement for young hypogonadal men. However, a prospective study of 60 male adolescents, with CH on gonadotrophin therapy for induction of spermatogenesis, showed similar spermatogenesis outcomes between those exposed to testosterone for puberty induction and those not previously exposed to testosterone.…”

Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis

“…Its half-life is not long enough to sustain the entire therapeutic period. Corifollitropin alfa should be administered once every 2 weeks in combination with hCG injections twice weekly in men with HH (11). We attempted to apply SAFA technology to invent long-acting biologics using FSH as a model.…”

“…Corifollitropin alfa, the longest-acting FSH available in clinics, has an approximately 1.5-to 2-fold longer elimination half-life than FSH (9). Previous studies have shown that long-acting FSH can effectively and safely replace FSH in the treatment regimen of adult men with HH desiring improved fertility (8,11).…”