Ovarest is an oral treatment for endometriosis being developed by Enteris BioPharma. It contains leuprolide, a synthetic form of gonadotropin-releasing hormone (GnRH).

How Ovarest works

Leuprolide, the active ingredient in Ovarest, disrupts the hormonal cycle associated with menstruation. This cycle begins with GnRH, which is normally released in pulses from an area of the brain called the hypothalamus. GnRH binds to its receptors in the pituitary gland and stimulates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These hormones, in turn, cause the egg follicle to develop in the ovary and be released (ovulation). They also stimulate the production of estrogen and progesterone.  

Endometriosis is characterized by the abnormal growth outside the uterus of tissue resembling the lining of the uterus (the endometrium), forming lesions. This abnormal tissue responds to hormonal changes that occur during the menstrual cycle in the same way as the normal endometrium. Because estrogen is responsible for the thickening of the endometrium, reducing its production can prevent endometrial lesions from growing. This reduces the symptoms of endometriosis.

Ovarest disrupts the pattern of GnRH pulses, which desensitizes the pituitary gland’s GnRH receptors. This reduces the production of FSH and LH. As a result, less estrogen is released. This prevents menstruation and shrinks the endometrial tissue, which reduces pain and inflammation in women with endometriosis.

An injectable form of leuprolide has been in use since the 1980s under various trade names, including Lupron Depot. Leuprolide is a protein and therefore is usually injected, because proteins are typically broken down in the digestive tract or have difficulty being absorbed into the bloodstream.

Ovarest is notable because it can be taken orally as a tablet.  Enteris used its patented delivery technology, Peptelligence, to package leuprolide so that it can still be effective when taken by mouth. Taking a daily tablet is usually more convenient for patients than going in to see their doctor for an injection once per month.

Ovarest in clinical trials

A Phase 2a clinical trial (NCT02807363) that had tested the pharmacokinetics (movement in the body) and pharmacodynamics (effect on the body) of Ovarest in healthy volunteers has now been completed.

The study enrolled 32 participants, who were randomly assigned to one of four treatment groups. Patients received either 4 mg of Ovarest once per day, 4 mg of Ovarest twice per day, 10 mg of Ovarest twice per day, or one injection of Lupron Depot in its approved preparation of leuprolide. Levels of the medication and estrogen in the blood were evaluated over the course of 28 days.

The results of the trial were promising, with women treated with Ovarest having a significant reduction in estrogen secretion.

Enteris now is planning to examine the efficacy and safety of Ovarest in women with endometriosis. The company also will determine whether Ovarest may be an effective treatment for other conditions such as uterine fibroids and prostate cancer.


Last updated: August 6, 2019

