Stuart Sealfon, MD

A drug that recently received approval from the U.S. Food and Drug Administration (FDA) for the treatment of pain associated with the gynecological disorder endometriosis had its genesis two decades ago in the laboratory of Stuart Sealfon, MD, at the Icahn School of Medicine at Mount Sinai.

The drug, Orilissa™, approved by the FDA in July, is the first oral regimen that specifically helps to ease the moderate to severe pain that accompanies endometriosis, a condition where the tissue that forms in the lining of the uterus continues to grow outside the uterus.

The disorder, which affects roughly one in ten women of reproductive age, negatively impacts quality of life, since the excess tissue growth is often accompanied by pain during menstruation, intercourse, or urination.

“Orilissa is a drug that resulted from the basic research we conducted at Mount Sinai, and it will help millions of women,” says Dr. Sealfon, Sarah B. and Seth M. Glickenhaus Professor and Chair Emeritus of the Department of Neurology. “At Mount Sinai, we discovered how to clone the drug target that was needed to develop this new drug.”

Indeed, as a young researcher more than two decades ago, Dr. Sealfon led the Mount Sinai team that cloned the gonadotropin-releasing hormone receptor (GnRHR) and genetically engineered host cells that express GnRHR. Gonadotropin-releasing hormone (GnRH), which is secreted by the hypothalamus, plays a key role in controlling reproduction, and acts via its receptor GnRHR.

The cloning procedure and primary structure of the receptor were described in two studies authored by Dr. Sealfon in 1992 and 1993, which were published in Molecular Endocrinology and Molecular and Cellular Endocrinology, respectively. The research provided a better understanding of the complex interplay of hypothalamic, pituitary, and gonadal hormones, which underlie pharmacotherapy and the reproductive system.

At the time, Dr. Sealfon says, a career-development grant provided him with the funding he needed to conduct his research. Two U.S. patents, in 1998 and 1999, assigned these inventions to Mount Sinai.

The oral application of Orilissa—also known by its generic name, elagolix—enables women to dial down the reproductive system. The dose-dependent drug suppresses the luteinizing hormone and the follicle-stimulating hormone, which leads to decreased blood concentrations of estradiol and progesterone. This reduces the growth of excess tissue, or lesions that form on the ovaries, fallopian tubes, or areas near the uterus, including the bowel and bladder that characterize endometriosis and cause pain.

The 20 years it took for elagolix to move from Dr. Sealfon’s laboratory to the marketplace demonstrates the length of time it can take for basic scientific discoveries to bear fruit, experts say. The drug was released by AbbVie, a global pharmaceutical company, in cooperation with Neurocrine Biosciences, Inc.

Endometriosis is considered one of the most common gynecologic disorders in the United States, but women can sometimes go years before having the laparoscopic procedure needed to render a proper diagnosis. In addition to the use of oral contraceptives, treatments have included nonsteroidal anti-inflammatory drugs, and opioids. In more extensive cases, women may undergo surgical procedures, including a hysterectomy.

In two Phase 3 clinical trials, Orilissa has been shown to be helpful in the treatment of uterine fibroids, as well. Fibroids are a common benign tumor that causes bleeding or pain in millions of women, and for which there are, currently, limited nonsurgical treatment options.

In the years since his initial discovery, Dr. Sealfon’s lab has continued to study GnRH receptor-mediated gonadotropin regulation and help guide future work in the field.