MVT-602

What is MVT-602?#

MVT-602 (TAK-448/RVT-602) is a synthetic nonapeptide agonist of the kisspeptin-1 receptor (KISS1R) developed by Myovant Sciences. It is an analog of the endogenous neuropeptide kisspeptin, which plays a central role in regulating the hypothalamic-pituitary-gonadal (HPG) axis by stimulating gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus.

The primary clinical application under investigation is as an oocyte maturation trigger during IVF and medically assisted reproduction (MAR). Current IVF protocols typically use hCG or GnRH agonists to trigger final oocyte maturation, but both carry limitations: hCG has a long half-life that sustains excessive ovarian stimulation and carries significant OHSS risk, while GnRH agonists produce only a brief LH surge that may be insufficient for optimal oocyte maturation in some patients.

MVT-602 addresses these limitations by producing a prolonged, physiological LH surge through endogenous GnRH activation. Its LH surge peaks at 21-22 hours (versus 4.7 hours for native kisspeptin-54) with a 4-fold greater LH exposure, while still working through the body's own regulatory pathways rather than bypassing them.

Mechanism of Action#

Kisspeptin-GnRH-LH Pathway#

MVT-602 activates the KISS1R receptor on GnRH neurons in the hypothalamus. This triggers the following cascade:

1. KISS1R activation: MVT-602 binds to and activates KISS1R on GnRH neurons in the arcuate nucleus and anteroventral periventricular nucleus
2. GnRH release: Activated GnRH neurons release endogenous GnRH into the hypothalamic-hypophyseal portal system
3. LH surge: GnRH stimulates pituitary gonadotrophs to release LH (and FSH) in a pulsatile pattern that mimics the natural mid-cycle LH surge
4. Oocyte maturation: The LH surge triggers final oocyte maturation and ovulation

Advantages Over Direct Triggers#

Because MVT-602 works upstream through the physiological kisspeptin-GnRH-LH cascade rather than directly activating LH receptors (like hCG), the ovulatory signal is self-limiting and regulated by normal feedback mechanisms. This may explain the reduced OHSS risk observed with kisspeptin-based triggering approaches.

Enhanced Duration#

MVT-602 has a longer half-life (approximately 108 minutes) compared to native kisspeptin-54 (approximately 28 minutes). Key modifications including D-amino acids, hydroxyproline, azaglycine, and methylated arginine provide resistance to enzymatic degradation, producing a markedly prolonged pharmacodynamic response.

Research Overview#

MVT-602 has been evaluated in Phase 1 and Phase 2a clinical trials in healthy premenopausal women. The Phase 1 study demonstrated dose-related LH increases with a prolonged surge profile, while the Phase 2a study showed similar results in the context of ovarian stimulation. Myovant Sciences was subsequently acquired by Sumitovant Biopharma (Sumitomo Pharma), and the continued development pathway for MVT-602 remains under their direction.

Important Considerations#

• MVT-602 is an investigational compound not approved for clinical use
• All data are from early-phase trials in small populations of healthy volunteers
• The compound has not been tested in actual IVF egg retrieval cycles to demonstrate clinical outcomes (pregnancy rates, OHSS rates)
• Kisspeptin-based triggers are an active area of research but not yet standard of care
• MVT-602's position relative to other kisspeptin analogs in development is evolving

Key Research Findings#

Kisspeptin Receptor Agonist Has Therapeutic Potential for Female Reproductive Disorders, published in Journal of Clinical Investigation (MacLean DB et al., 2020; PMID: 33196464):

Preclinical and Phase 1 clinical evaluation of MVT-602 demonstrating potent KISS1R agonism and a prolonged LH surge profile in healthy premenopausal women, with peak LH at 21-22 hours versus 4.7 hours for kisspeptin-54.

• MVT-602 produced dose-related LH increases in healthy premenopausal women
• Peak LH at 21-22 hours vs 4.7 hours for kisspeptin-54
• LH AUC approximately 4-fold greater than kisspeptin-54

Endocrine Profile of the Kisspeptin Receptor Agonist MVT-602 in Healthy Premenopausal Women With and Without Ovarian Stimulation, published in Fertility and Sterility (Sheridan R et al., 2023; PMID: 37925096):

Combined results from Phase 1 (follicular phase) and Phase 2a (after ovarian stimulation) trials of MVT-602 in healthy premenopausal women. Confirmed the prolonged LH surge profile in both settings.

• Confirmed prolonged LH surge in both unstimulated and stimulated settings
• LH surge close to natural mid-cycle LH surge after ovarian stimulation
• High rates of ovulation observed in Phase 2a

Related Reading#

• MVT-602 research studies and evidence
• MVT-602 dosing protocols
• MVT-602 side effects profile
• Kisspeptin research guide
• Gonadorelin research guide