ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 OC6.1 | DOI: 10.1530/endoabs.65.OC6.1

Effect of MVT-602, a potent kisspeptin receptor agonist, on LH levels in healthy pre-menopausal women undergoing a minimal controlled ovarian stimulation protocol

Ali Abbara1, Ingrid Duijkers2, Max Ezzati3, Christine Voors4, Christel Romeijn4, Lance Berman5, Xiaolin Fan6, Elizabeth Migoya6 & Waljit S Dhillo1

1Imperial College London, London, UK; 2Dinox Consultancy bv, Groningen, Netherlands; 3Palo Alto Medical Foundation, Palo Alto, USA; 4QPS Netherlands BV, Groningen, Netherlands; 5Develop BioPharma Consulting, Barcelona, Spain; 6Myovant Sciences- Inc., Brisbane, USA

Background: Kisspeptin is an endogenous neuropeptide that regulates GnRH release from the hypothalamus. Kisspeptin-54 has been shown to effectively trigger oocyte maturation during in vitro fertilisation (IVF) treatment, but with markedly reduced rates of ovarian hyperstimulation syndrome (OHSS). The kisspeptin receptor agonist, MVT-602, has a longer half-life than native kisspeptin-54 (1.5–2.2 h vs. 0.5 h) and has potential for development as a novel trigger of oocyte maturation. LH concentrations following kisspeptin-54 are augmented during controlled ovarian stimulation (COS); thus we investigated the LH-profile of MVT-602 in the context of a minimal COS protocol.

Methods: A randomised, double-blind, placebo and active comparator-controlled, phase 2a study was conducted (May-October 2018). Seventy-five healthy women (aged <36 years, BMI 18–30 kg/m2) underwent minimal COS (recombinant FSH / GnRH antagonist). Once the dominant follicle reached ≥17 mm, women were randomised to receive a single subcutaneous dose of MVT-602 (0.1, 0.3, 1.0 or 3.0 μg; n=16-17 per group), GnRH agonist triptorelin 0.2 mg (n=5), or placebo (n=5) in a 3:1:1 ratio. Hormone levels were monitored every 2–4 h for 48 h and then daily for 13 days, or until ovulation was confirmed.

Results: MVT-602 induced an LH surge that peaked at 16–24 h to ˜50 IU/l and provided LH-exposure for more than 48 h. Doses of MVT-602 of 0.3 mcg or greater increased LH sooner and with greater consistency. The proportion of women who ovulated within 5 days of trigger administration increased with dose of MVT-602 (Placebo 60%, 0.1 μg 75%, 0.3 μg 82%, 1 μg 88%, 3 μg 100%). LH-rise after GnRH agonist was more pronounced (peak LH >150 IU/l) and occurred sooner (˜4 h) than following MVT-602.

Conclusion: The LH-profile following MVT-602 more closely mirrored that of the natural mid-cycle LH surge providing LH-exposure for >48 h. Thus, MVT-602 could offer an advantageous profile in the triggering of oocyte maturation during IVF treatment.

Trial registration number: 2018-001379-20