Myovant Sciences and Pfizer Initiate Phase 3 SERENE Trial of Relugolix Combination Tablet for Contraception in High-Risk Women

April 13, 2021 News /BioValleyBIOON/ --PfizerPfizer and Myovant Sciences recently announced that the first participant has been dosed in the Phase 3 SERENE study. This study is evaluating the contraceptive efficacy of the relugolix combination tablet (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) in healthy women aged 18 to 35 years at risk of pregnancy. Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist. Currently, the New Drug Application (NDA) for the relugolix combination tablet for the treatment of uterine fibroids in women is under review by the U.S.FDAreview, with a decision expected before the target action date of June 1, 2021. In addition, Pfizer and Myovant plan to submit a new drug application for relugolix combination tablets for the treatment of moderate to severe pain associated with endometriosis in the first half of 2021.

Juan Camilo Arjona Ferreira, M.D., Chief Medical Officer of Myovant Sciences, stated: “We are committed to redefining care for women, which means supporting their overall health and quality of life. Many women with uterine fibroids and endometriosis need to simultaneously manage their symptoms and reproductive choices, including contraception. The Phase 3 SERENE study is designed to evaluate the potential of relugolix combination tablets to prevent pregnancy and will complement the data from our Phase 3 LIBERTY and SPIRIT programs, which confirmed the promise of relugolix combination tablets as a potential treatment for uterine fibroids and endometriosis.”

The SERENE study will enroll 900 sexually active, healthy women aged 18–35 years with normal fertility. The primary efficacy endpoint is the Pearl Index, defined as the number of on-treatment pregnancies per 100 women using a specific contraceptive method for one year. On-treatment pregnancy refers to pregnancies with an estimated date of conception occurring from the first day of study intervention up to and including seven days after the last dose of the study drug. Participants will receive once-daily relugolix combination tablets for 13 cycles, each consisting of 28 days, constituting high-risk cycles. Safety data will also be collected during the study.

In April 2020, Myovant announced the results of a Phase 1, single-arm, open-label study on ovulation suppression, which aimed to evaluate the effect of relugolix combination tablets on ovulation suppression based on the Hoogland-Skouby assessment scale (score <5). Among 67 healthy women, after 84 days of treatment (3 cycles), relugolix combination tablet therapy achieved 100% ovulation suppression and was generally well-tolerated. Furthermore, 100% of the women resumed ovulation or menstruation after stopping treatment, with an average time to ovulation of 23.5 days. The data from this study were presented at the American Society for Reproductive Medicine (ASRM) 2020 Virtual Congress.

James Rusnak, M.D., Senior Vice President of Global Product Development and Chief Development Officer at Pfizer, stated, “The results from the Phase 1 study demonstrated that the relugolix combination tablet suppressed ovulation in all study participants, laying the foundation for the SERENE study to evaluate the potential of the relugolix combination tablet to prevent pregnancy in women undergoing treatment. Data from this Phase 3 study will provide critical information to guide treatment decisions for women with endometriosis and uterine fibroids.”

Chemical Structure and Mechanism of Action of Relugolix (Structure image source: medchemexpress.com)

In December 2020, Pfizer and Myovant Sciences entered into a collaboration agreement valued at $4.2 billion to develop and commercialize relugolix for oncology and women’s health in the United States and Canada. Pfizer will also obtain rights to commercialize relugolix outside the United States and Canada (excluding certain Asian countries) forTumorExclusive option rights in the academic field.

Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist that inhibits testicular testosterone production, a hormone that can stimulate the growth of prostate cancer cells. Additionally, relugolix reduces ovarian estradiol production by blocking GnRH receptors in the pituitary gland; this hormone is known to stimulate the growth of uterine fibroids and endometriosis.

Relugolix was developed by Takeda. In June 2016, Myovant Sciences (a company established by Roivant and Takeda) obtained exclusive global rights, excluding Japan and other Asian countries. In Japan, relugolix was approved in January 2019 and marketed under the brand name Relumina for the improvement of the following symptoms caused by uterine fibroids: menorrhagia, lower abdominal pain, low back pain, andAnemia。

Prostate Cancer/Uterine Fibroids/Endometriosis (Images sourced from: istockphoto.com, clinicaladvisor.com, insider.com)

Currently, Myovant is developing once-daily oral relugolix tablets (120 mg) for the treatment of advanced prostate cancer. On December 18, 2020, Orgovyx (relugolix, 120-mg tablets) received U.S.FDAApproved for the treatment of adult patients with advanced prostate cancer.

It is worth mentioning that Orgovyx is the United StatesFDAThe first and only oral GnRH receptor antagonist approved for the treatment of advanced prostate cancer. The drug was approved through the Priority Review program. In the Phase 3 HERO study, relugolix demonstrated a response rate of up to 96.7%, significantly superior to leuprolide acetate (88.8%), while reducing the risk of major adverse cardiovascular events (MACE) by 54%.

In addition, Myovant is also developing a once-daily oral combination tablet of relugolix (relugolix 40 mg, estradiol 1.0 mg, and norethisterone acetate 0.5 mg) for the treatment of uterine fibroids and endometriosis in women. Currently, the relugolix combination tablet for the treatment of uterine fibroids in women is under review by the U.S. FDA, with a target action date of June 1, 2021. The relugolix combination tablet for the treatment of endometrial cancer is expected to be submitted to the U.S.FDASubmit New Drug Application. (Bioon.com)

Original Source: Myovant Sciences and Pfizer Announce First Participant Dosed in Phase 3 SERENE Study Evaluating Contraceptive Efficacy of Once-Daily Relugolix Combination Tablet