A new drug called MVT-602, which mimics the kisspeptin hormone, safely triggers a strong LH surge and ovulation in healthy women, working about as well as the standard drug triptorelin but with a short half‑life. The study shows that a single sub‑cutaneous dose of 3 µg reliably caused ovulation within 3‑4 days, while lower doses were still effective but less consistent.

Kisspeptin is an essential regulator of hypothalamic gonadotropin-releasing hormone release and is required for physiological ovulation. Native kisspeptin-54 can induce oocyte maturation during in vitro fertilization treatment, including in women who are at high risk of ovarian hyperstimulation syndrome. MVT-602 is a potent kisspeptin receptor agonist with prospective utility to treat anovulatory disorders by triggering oocyte maturation and ovulation during medically assisted reproduction (MAR). Currently, the endocrine profile of MVT-602 during ovarian stimulation is unreported. To determine the endocrine profile of MVT-602 in the follicular phase of healthy premenopausal women (phase-1 trial), and after minimal ovarian stimulation to more closely reflect the endocrine milieu encountered during MAR (phase-2a trial). Two randomized, placebo-controlled, parallel-group, dose-finding trials. Clinical trials unit. Healthy women aged 18-35 years, either without (phase-1; n = 24), or with ovarian stimulation (phase-2a; n = 75). Phase-1: single subcutaneous dose of MVT-602 (0.3, 1.0, or 3.0 μg) or placebo, (n = 6 per dose). Phase-2a: single subcutaneous dose of MVT-602 (0.1, 0.3, 1.0, or 3.0 μg; n = 16-17 per dose), triptorelin 0.2 mg (n = 5; active comparator), or placebo (n = 5). Phase-1: safety/tolerability; pharmacokinetics; and pharmacodynamics (luteinizing hormone [LH] and other reproductive hormones). Phase-2a: safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones); and time to ovulation assessed by transvaginal ultrasound. In both the trials, MVT-602 was safe and well tolerated across the entire dose range. It was rapidly absorbed and eliminated, with a mean elimination half-life of 1.3-2.2 hours. In the phase-2a trial, LH concentrations increased dose dependently; mean maximum change from baseline of 82.4 IU/L at 24.8 hours was observed after administration of 3 μg MVT-602 and remained >15 IU/L for 33 hours. Time to ovulation after drug administration was 3.3-3.9 days (MVT-602), 3.4 days (triptorelin), and 5.5 days (placebo). Ovulation occurred within 5 days of administration in 100% (3 μg), 88% (1 μg), 82% (0.3 μg), and 75% (0.1 μg), of women after MVT-602, 100% after triptorelin and 60% after placebo. MVT-602 induces LH concentrations of similar amplitude and duration as the physiological midcycle LH surge with potential utility for induction of oocyte maturation and ovulation during MAR. EUDRA-CT: 2017-003812-38, 2018-001379-20.