TherapeuticsMD Announces FDA Approval of Imvexxy (estradiol vaginal inserts) for the Treatment of Dyspareunia Due to Menopause

In continuation of my update on estradiol

TherapeuticsMD, Inc., an innovative women's healthcare company,  announced that the United States Food and Drug Administration (FDA) has approved Imvexxy (estradiol vaginal inserts) for the treatment of moderate-to-severe dyspareunia (vaginal pain associated with sexual activity), a symptom of vulvar and vaginal atrophy (VVA), due to menopause. Imvexxy is the only product in its therapeutic class to offer a 4 mcg and 10 mcg dose, the 4 mcg representing the lowest approved dose of vaginal estradiol available.

"Imvexxy is a bio-identical vaginal estrogen product that offers a fraction of the estrogen contained in the average doses of many existing products currently on the market," said Brian Bernick, MD, Chief Clinical Officer of TherapeuticsMD. "Imvexxy is the only product specifically designed to be applicator-free. It dissolves completely without mess or additional clean-up, and can be used anytime of day. It allows women the freedom to immediately return to their normal daily activities. Studies showed that, in patients who used Imvexxy, systemic absorption of estradiol remained within postmenopausal range."

"We are excited to bring Imvexxy to market as TherapeuticsMD's first FDA-approved drug as we strive to be the premier Women's Health Company," said Robert Finizio, Chief Executive Officer of TherapeuticsMD. "Imvexxy reflects our long-standing corporate mission and commitment to health solutions that women want, based on the concepts of medical need, efficacy, safety, simplicity, and affordability. Imvexxy will be offered at a price in parity with other products that have been on the market for 10 to 30 years. By ensuring patients can access Imvexxy at an affordable price, TherapeuticsMD is doing the right thing for women."

FDA Approves Annovera (segesterone acetate and ethinyl estradiol) Vaginal Contraceptive System

In continuation of my update on ethinyl estradiol

         

Segesterone acetate       

                                

                                                                              Ethinylestradiol 

The Population Council, a global nonprofit research organization, announced it has received U.S. Food and Drug Administration (FDA) approval for Annovera (segesterone acetate and ethinyl estradiol vaginal system), the first and only contraceptive that provides an entire year of protection against unintended pregnancy while fully under a woman's control. The approval marks an important step toward expanding contraceptive options for women.

Annovera is the first in a new class of contraceptives. It is a soft, reusable, flexible silicone ring (2 ¼ inches diameter) that can be inserted and removed by a woman herself. Left in place for 21 days and removed for 7 days each cycle, it is indicated to prevent pregnancy for up to a year and does not require refrigeration, which is particularly important for distribution and use in low-resource settings. Annovera has not been adequately evaluated in women with a body mass index (BMI) greater than 29 kg/m2.

"Nearly half of all pregnancies in the U.S. are unintended, which can increase health risks for mom and baby," said Population Council President, Julia Bunting. "For more than 60 years, the Population Council has been at the vanguard of global efforts to develop innovative family planning methods that meet women's needs. Having a single contraceptive system that provides a full year of protection while under a woman's control could be a game-changer for some women."

According to the Center for Disease Control, more than 43 million women in the U.S. are at risk of unintended pregnancy. Women with unintended pregnancies are less likely to receive proper prenatal care; are more likely to have premature and low-birth-weight infants; and have increased physical and mental health risks. Providing women with a range of contraceptive options that better meet their family planning needs helps reduce unintended pregnancy and improves outcomes.

"I am delighted to have Annovera as a new family planning option for women who want greater choice, convenience and control," said Anita Nelson, M.D., professor and chair, Obstetrics and Gynecology Western University Health Sciences and a principal investigator of the Phase 3 trials. "The Population Council has been a leader in creatively and collectively addressing women's contraceptive needs. It is exciting they are continuing to help empower women with another contraceptive choice."

The FDA approval of Annovera is based in part on data from 17 clinical trials, including two pivotal Phase 3 safety and efficacy trials. The Phase 3 program enrolled a total of 2,308 women across 27 study sites in the United States, Latin America, Europe, and Australia. Women in the trials were between 18 and 40 years of age and were instructed to use the system over 13 menstrual cycles, or one full year. The Primary Endpoint Pearl Index was 2.98. The data show that Annovera is 97.3% effective in preventing pregnancy when used as directed. Annovera offers a similar risk profile to other combined hormonal contraceptives, including a boxed warning related to increased cardiovascular risk when used while smoking.

In formulating Annovera, researchers at the Population Council's Center for Biomedical Research combined a new progestin (segesterone acetate) with a widely used estrogen (ethinyl estradiol) to develop a single product that can inhibit ovulation for an entire year. A sub-set study of women in the Phase 3 clinical trials ranked Annovera highly in terms of convenience, ease of use and comfort. Nearly 9 in 10 women (89%) surveyed were satisfied with it as a method of contraception. Most participants surveyed experienced no change in sexual pleasure or frequency of sexual intercourse.

"This approval is a key first step toward introducing this product globally and better meeting the sexual and reproductive health needs of women, men and young people in the U.S. and around the world," said Jim Sailer, executive director, Center for Biomedical Research at the Population Council. "We are grateful to the dozens of researchers who have worked on this product, the donors who have funded its development, and most of all, to the thousands of women who volunteered to participate in clinical trials and made this all possible."

Important public and private donors from around the world have supported the research and development of Annovera, including the United States Agency for International Development (USAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the Bill & Melinda Gates Foundation, the Avis and Clifford Barrus Medical Foundation, the World Health Organization (WHO), and the Population Council.

Recently, the Population Council announced a license agreement with TherapeuticsMD, an innovative healthcare company focused exclusively on women's health, to make Annovera available to women in the U.S. Through the license agreement, TherapeuticsMD will provide significantly reduced pricing to federally designated Title X family planning clinics serving lower-income women. TherapeuticsMD currently estimates Annovera will be commercially available as early as the third quarter of 2019 and commercially launched as early as the fourth quarter of 2019 or first quarter of 2020. Proceeds from the license agreement will be reinvested into the Population Council's continued research and development programs. The Population Council is continuing efforts to make Annovera available worldwide, including in low- and middle-income countries where more than 214 million women have an unmet need for contraception.

Annovera will be the sixth contraceptive technology that Population Council researchers have developed to address family planning needs around the world and brought to market through commercialization agreements. We estimate that more than 170 million women worldwide are currently using highly effective contraceptives developed by the Population Council or based on our technologies. Other Population Council-developed contraceptives include: the copper IUD ParaGard®; intrauterine system Mirena®; contraceptive implants Norplant® and Jadelle®; and Progering®, the contraceptive vaginal ring for breastfeeding women.

Ref : https://en.wikipedia.org/wiki/Segesterone_acetate

https://en.wikipedia.org/wiki/Ethinylestradiol

FDA Approves EluRyng (etonogestrel/ethinyl estradiol vaginal ring), the First Generic NuvaRing

Amneal Pharmaceuticals, Inc. (NYSE: AMRX) (“Amneal” or the “Company”) announced that it has received Abbreviated New Drug Application (ANDA) approval from the U.S. Food and Drug Administration (FDA) for EluRyng™ (etonogestrel/Ethinyl estradiol vaginal ring), the first generic version of NuvaRing®. Amneal has initiated commercialization activities for EluRyng, which is being manufactured internally and launching today.

We are pleased to announce FDA approval of EluRyng, one of 15 new, complex products we expect to launch over the next 18 to 24 months,” said Chirag and Chintu Patel, Co-Chief Executive Officers. “This milestone underscores Amneal’s deep scientific and regulatory capabilities and our ability to overcome significant barriers to entry, including complex formulation development and specialized manufacturing requirements. In addition, EluRyng adds a differentiated, complex dosage form to our portfolio, and bringing this product to market reflects our commitment to improving affordable access to complex drug products. Looking ahead, we remain enthusiastic about the additional high-value opportunities in our pipeline that are designed to improve the lives of patients and drive meaningful growth and value-creation for our shareholders and other stakeholders in 2020 and beyond.”

According to IQVIA™, a leading healthcare data and analytics provider, NuvaRing U.S. annual sales for the 12 months ended October 31, 2019 were approximately $976 million.
About Amneal

Amneal Pharmaceuticals, Inc. (NYSE: AMRX), headquartered in Bridgewater, NJ, is a fully-integrated pharmaceutical company focused on the development, manufacture and distribution of generic and specialty drug products. The Company has manufacturing operations in North America, Asia, and Europe, working together to bring high-quality medicines to patients primarily within the United States.

Amneal has an extensive portfolio of more than 300 generic medicines and is expanding its portfolio to include complex dosage forms, including biosimilars, in a broad range of therapeutic areas. The Company also markets a portfolio of branded pharmaceutical products through its Specialty segment focused principally on the central nervous system and endocrine disorders. For more information, visit www.amneal.com.

https://www.webmd.com/drugs/2/drug-63403/etonogestrel-ethinyl-estradiol-vaginal/details

Avion Pharmaceuticals Announces FDA Approval of Balcoltra (levonorgestrel and ethinyl estradiol tablets and ferrous bisglycinate tablets) Oral Contraceptive

 

Avion Pharmaceuticals, LLC, the makers of the Prenate® line of prescription prenatal vitamins, received approval of its new drug application (NDA) for the oral contraceptive Balcoltra (levonorgestrel and ethinyl estradiol tablets and ferrous bisglycinate tablets), the company's first internally developed NDA. Avion expects to commercially launch this new oral contraceptive to the prescribing community in Spring 2018.

The approval of Balcoltra, the only branded oral contraceptive combining 0.1 mg levonorgestrel, 20 mcg ethinyl estradiol tablets and ferrous bisglycinate tablets 36.5 mg, marks a milestone for Avion Pharmaceuticals and a win for the women's health category by allowing women to have access to a clinically effective form of oral contraception for pregnancy prevention.

"Avion is excited to offer our women's health community this oral contraceptive formulation that fills a gap in the current branded options available to women," stated Art Deas, CEO of Avion. "The validity of data related to safety and efficacy for Balcoltra also provides another viable prescribing option for our prescribing community," added Deas.

"Avion has always focused on creating a meaningful and long-term supporting role for our women's healthcare prescribers," added Avion President Mike Sullivan. "The Balcoltra™ approval and forthcoming launch is a monumental event for Avion, allowing us to solidify our commitment to the women's healthcare community."

Ref :





Avion Pharmaceuticals Announces FDA Approval of Balcoltra (levonorgestrel and ethinyl estradiol tablets and ferrous bisglycinate tablets) Oral Contraceptive

Obseva Announces U.S. FDA Acceptance of New Drug Application for Linzagolix

Obseva SA   announced   the New Drug Application (NDA) for linzagolix for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women has been accepted for review by the United States Food and Drug Administration (FDA). The submission is based on data from the two Phase 3 PRIMROSE trials. Linzagolix has a differentiated profile and if approved, would be the first and only GnRH receptor antagonist with flexible dosing options for uterine fibroids, including a low dose option to address the needs of women who cannot or do not want to take hormones.1,4 The FDA set a target action date of September 13, 2022 for this NDA under the Prescription Drug User Fee Act (PDUFA).

“Today marks an important milestone not only in the linzagolix clinical development process, but for Obseva as a company, and most importantly, the millions of women living with uterine fibroids throughout the US. Linzagolix is a significant innovation in the field of women’s health – an area that is consistently underinvested in – and we are incredibly excited about the potential of bringing this important treatment to market” said Brian O’Callaghan, CEO of Obseva. “We are encouraged by our positive Phase 3 PRIMROSE results. If approved, we believe linzagolix will address a significant unmet need in offering a more individualized treatment option for a broader range of women.”

The Phase 3 PRIMROSE trials of linzagolix (PRIMROSE 1: US; n=574 and PRIMROSE 2: Europe and US; n=535) investigated the efficacy and safety of two dosing regimens, 100mg once daily and 200mg once daily, alone or in combination with hormonal ABT (1 mg estradiol and 0.5 mg norethisterone acetate) for the treatment of heavy menstrual bleeding associated with uterine fibroids. The NDA submission comprises positive 24-week treatment results from both studies, as well as supportive results from Week 52 and the 76-week post-treatment follow-up.

“Uterine fibroids can have a devastating impact on women’s day-to-day life. With its unique dosing options, linzagolix has the potential to significantly advance medical options for women,” stated Elizabeth Garner, MD, MPH, Chief Medical Officer of Obseva. “A dosing option without hormonal ABT would be welcomed by the significant number of women who either have contraindications to or a personal preference to avoid the use of estrogen-based therapies, while also providing a dosing option for women in whom hormonal ABT is indicated.”

The linzagolix marketing authorization application (MAA) was validated by the European Medicine Agency (EMA) with an approval recommendation from the Committee for Medicinal Products for Human Use (CHMP) expected in Q4 2021. Obseva announced previously that the company has entered into a partnership with Syneos Health to support commercialization of linzagolix in the US and EU.

https://en.wikipedia.org/wiki/Linzagolix

https://www.drugs.com/nda/linzagolix_211122.html

Molecule Found That Inhibits Estrogen, Key Risk Factor for Endometrial and Breast Cancers

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered a molecule, KLF15 (see structure) that inhibits the action of estrogen. This female hormone plays a key role in the growth, maintenance and repair of reproductive tissues and fuels the development of endometrial and breast cancers. The molecule, discovered in animal studies, could lead to new therapies for preventing and treating estrogen-related diseases in humans.

In studies involving rodents, Dr. Pollard discovered that a molecule called KLF15 (Kruppel-like transcription factor-15) controls the actions of estradiol and progesterone in the endometrium by inhibiting the production MCM2, a protein involved in DNA synthesis.

 

"Our findings raise the possibility that it may be possible to prevent or treat endometrial and breast cancer and other diseases related to estrogen by promoting the action of KLF15," said Dr. Pollard.

The paper, titled "KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing," is coauthored by Sanhita Ray, Ph.D., a postdoctoral fellow at Einstein.

More....

Molecule Found That Inhibits Estrogen, Key Risk Factor for Endometrial and Breast Cancers

FDA Approves Nextstellis (drospirenone and estetrol) Oral Contraceptive for Birth Control

In continuation of my update on drospirenone

"When speaking with patients about their contraceptive options, one of the most common concerns is side effects," said Mitchell Creinin, Professor and Director of Family Planning at the University of California, Davis. "Nextstellis is an innovative contraceptive that has been shown to be not only safe and effective, but also well tolerated in clinical trials with a desirable bleeding profile and minimal impact on triglycerides, cholesterol, and glucose, as well as weight and endocrine markers."

Nearly 10 million American women use short-acting combination contraceptives (estrogen and progestin). Of these contraceptives, more than 99% contain ethinyl estradiol (EE), a synthetic estrogen that binds widely to all estrogen receptors in the body.
Nextstellis is the only oral contraceptive to contain E4; E4 acts differently than other estrogens and is the first estrogen to be described as a NEST:  A Native Estrogen with Selective actions in Tissues. It has more selective activity in tissues, focusing on those needed to support contraceptive efficacy, cycle control and other beneficial effects of estrogen. Nextstellis pairs E4, which has a long half-life (24-28 hours), with the proven progestin drospirenone, specifically chosen due to its long half-life (~30 hours) and its anti-androgenic and anti-mineralocorticoid properties.

"The approval of Nextstellis represents an important milestone in providing women with another choice for their reproductive health," said Scott Richards, CEO of Mayne Pharma. "We are delighted to be introducing a new estrogen and bringing to market this novel, safe and effective option for women to consider with their healthcare providers."

The comprehensive Nextstellis clinical study program included a diverse patient population with women both starting and switching birth control as well as patients with a body mass index (BMI) of up to 35 kg/m2. According to phase 3 study findings, Nextstellis demonstrated contraceptive efficacy across all subgroups by age, BMI and prior hormonal contraception use. Nextstellis was also associated with a favorable bleeding profile and low rates of breakthrough bleeding, including in cycle 1.

Nextstellis was developed by Mayne Pharma's development and manufacturing partner, Mithra Pharmaceuticals, SA. The company anticipates the commercial launch of Nextstellis by the end of June 2021.

Mayne Pharma announced today that the U.S. Food and Drug Administration (FDA) has approved Nextstellis (3 mg drospirenone [DRSP] and 14.2 mg estetrol [E4] tablets) for the prevention of pregnancy. Nextstellis is the first and only contraceptive pill containing E4, a naturally occurring estrogen, now produced from a plant source, with a unique mechanism of action that offers potential advantages over other estrogens.

https://en.wikipedia.org/wiki/Drospirenone