New Data Show NEXTSTELLIS® Has Selective Impact On Endocrine Markers Compared With Common Combined Oral Contraceptives

RALEIGH, N.C., March 6, 2021 /PRNewswire/ -- Mayne Pharma announced today new data showing treatment with NEXTSTELLIS®,¹ a novel, investigational combined oral contraceptive (COC) containing drospirenone (DRSP) and estetrol (E4), resulted in limited changes in endocrine markers, including lower increases in hormone binding globulins, compared with COCs based on ethinyl-estradiol (EE), the synthetic estrogen used in all but one of the marketed COCs. The data was presented at the annual meeting of the International Society for the Study of Women's Sexual Health (ISSWSH), held virtually in the U.S. from March 5-7. 

Historically, some COCs have been associated with a decrease in circulating androgensⁱ and increases in hormone binding globulins.ⁱⁱ These endocrine changes can result in hormonal imbalance and have been associated with side effects such as acne, excess facial and body hair, or changes in libido.ⁱⁱⁱ

"When prescribing COCs, practitioners must have a good understanding of how these therapies may impact other hormones in the body in order to make an informed prescribing decision for their patients," said Andrew London, M.D., Assistant Professor of OB/GYN at The Johns Hopkins School of Medicine. "Based on our findings, treatment with DRSP/E4 has limited effects on some of these endocrine parameters compared to the tested EE-containing products, giving DRSP/E4 a different and potentially favorable endocrine profile compared to those EE-based COCs."

In a phase 2 study, titled "Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone," the changes from the baseline serum concentration of various endocrine and liver protein markers at cycle 3 and 6 were determined in subjects receiving NEXTSTELLIS or a COC formulation containing EE combined with either levonorgestrel (LNG/EE) or drospirenone (DRSP/EE). Comparative findings include:

• A significant increase in sex hormone-binding globulin (SHBG) was observed at cycle 3 (240%) and 6 (251%) with DRSP/EE as compared to baseline or those observed with NEXTSTELLIS (52% and 55%). LNG/EE was not significantly different at cycle 3 or 6.
• At cycle 6, decrease in total testosterone (TT) and free testosterone (FT) with NEXTSTELLIS (31% and 50%) was not significantly different from those noted with LNG/EE (38% and 50%) or DRSP/EE (33% and 71%). At cycle 3, there were no decreases noted in any group.
• At cycle 6, NEXTSTELLIS had a significantly lower impact on dehydroepiandrosterone sulfate (DHEA-S) levels than DRSP/EE (10% vs. 27%). No differences were noted between DRSP/E4 and LNG/EE.

"This exciting new data adds to the solid safety and tolerability profile of NEXTSTELLIS and the growing body of clinical evidence that this unique combination with a new form of estrogen, may be a promising novel oral contraceptive option for women," said Scott Richards, CEO, Mayne Pharma.  

Study design
In the randomized, open-label, three-arm parallel study, participants received DRSP 3 mg/E4 15 mg (n = 38), LNG 150 mcg/EE 30 mcg (n = 29), or DRSP 3 mg/EE 20 mcg (n = 31) in a 24/4-day regimen of six consecutive, 28-day treatment cycles. Changes from baseline in serum TT, FT, androstenedione, DHEA-S, cortisol binding globulin (CBG), SHBG, and thyroxine binding globulin (TBG) were determined at cycle 3 and 6.

About NEXTSTELLIS®
Developed by Mayne Pharma's development and manufacturing partner Mithra Pharmaceuticals SA, NEXTSTELLIS® is a novel, investigational combined oral contraceptive pill containing 3 mg drospirenone (DRSP) and 15 mg estetrol (E4). E4 is a naturally occurring estrogen that is produced by the human fetal liver during pregnancy and can now be produced from a plant source. In June 2020, the U.S. Food and Drug Administration (FDA) accepted for review a New Drug Application (NDA) submitted by Mayne Pharma for NEXTSTELLIS to prevent pregnancy. The NDA submission included results from two phase 3 clinical studies conducted in more than 3,725 women aged 16 to 50 years. If approved, NEXTSTELLIS would be the first contraceptive product containing E4 and the first new estrogen introduced in the U.S. for contraceptive use in approximately 50 years.

About Mayne Pharma
Mayne Pharma is an ASX-listed specialty pharmaceutical company focused on applying its drug delivery expertise to commercialize branded and generic pharmaceuticals, offering patients better, safe and more accessible medicines. The company has an extensive women's health portfolio focused on contraceptives. Its pipeline includes a novel oral contraceptive and a number of branded generic contraceptives. Mayne Pharma also provides contract development and manufacturing services to more than 100 clients worldwide.

Mayne Pharma has a 40-year track record of innovation and success in developing new oral drug delivery systems and these technologies have been successfully commercialized in numerous products that continue to be marketed around the world.

NEXTSTELLIS® is a registered trademark of a third party.

Contact: Karen Dombek, [email protected], 908-234-9900

SOURCE Mayne Pharma