Oral GnRH antagonists have off-label potential in the female infertility space, beyond the indications of endometriosis-associated pain and uterine fibroids, which constitute the main development focus for companies competing in the space, says GlobalData. Due to their novel oral formulation, the company notes that GnRH antagonists could replace subcutaneous (SC) GnRH antagonists, which are commonly used in assisted reproductive technology (ART) protocols – leading to an expanded market opportunity.
Kelly Lambrinos, Managing Analyst at GlobalData comments, “Multiple competing companies have entered the female health space with their own oral GnRH antagonist – either approved or under development – attempting to capture market share, specifically for the indications of endometriosis and uterine fibroids. These include AbbVie/Neurocrine’s Orilissa (elagolix), Myovant/Takeda’s relugolix, and ObsEva’s linzagolix. Key opinion leaders* interviewed by GlobalData stated that they are enthusiastic about the potential to have this class of drugs in a convenient, oral formulation for the first time, and anticipate their off-label use in the infertility treatment setting if sufficient pituitary downregulation is demonstrated and the appropriate dosing is determined in experimental protocols.”
In the US, nearly 60 per cent of assisted reproductive technology (ART) cycles in the infertility treatment setting involve protocols in which pituitary downregulation is achieved with the use of SC GnRH antagonists, according to primary research conducted by GlobalData. In 2020, 79,286 short GnRH antagonist cycles are projected to occur in the US alone, increasing to 94,126 cycles by 2024, according to a GlobalData forecast.
Lambrinos continues, “GnRH antagonists allow for the rapid onset of estrogen suppression without the hormonal flare effect seen with GnRH agonists. The biggest advantage, however, is their oral route of administration. Oral GnRH antagonists could notably improve the experience of patients undergoing infertility treatment by reducing the need for daily SC injections, which are often a burden to patients. The oral route of administration also eliminates the need to mix or reconstitute SC formulas before each administration.”
While oral GnRH antagonists are targeted at pain associated with endometriosis, experts also see a place for them within the therapeutic paradigm of infertility-associated endometriosis. Ongoing trials are examining whether infertile women with endometriosis — a common cause of infertility — who are undergoing embryo transfer as part of an in vitro fertilization cycle may see an improvement in live birth rates when pretreated with a GnRH antagonist.
Lambrinos concludes, “Oral GnRH antagonists could become a newer alternative, with increased dosing convenience and fewer side effects, thus replacing the GnRH agonist therapies that are often used in this setting.”
* Key opinion leaders interviewed from across the US, France, Germany, Italy, Spain, the UK and Japan