New Efficacy Data Reinforces NEXTSTELLIS® Benefits Across Patient Populations

GREENVILLE, N.C., April 30, 2021 /PRNewswire/ -- Mayne Pharma announced today results from two studies showing treatment with NEXTSTELLIS® (3 mg drospirenone [DRSP] and 14.2 mg estetrol [E4] tablets) demonstrated contraceptive efficacy and excellent cycle control across subgroups, including age, body mass index (BMI)[1] and prior contraceptive use. NEXTSTELLIS is the first contraceptive pill containing E4, a new naturally occurring estrogen with a unique mechanism of action that offers potential advantages over other estrogens. The findings were presented at the 2021 American College of Obstetricians and Gynecologists (ACOG) Annual Clinical and Scientific Meeting, held virtually in the U.S. from April 30 – May 2.

"One of the basic assumptions for all combined oral contraceptives is a high efficacy rate in preventing pregnancy, yet clinical studies and real-world evidence have found that this efficacy is not always consistent across various subgroups," said Mitchell Creinin, M.D., Professor and Director of Family Planning at the University of California, Davis. "NEXTSTELLIS demonstrated a 98% efficacy and an overall Pearl Index of 2.65, reinforcing the product's effectiveness regardless of age, BMI or contraceptive history."

In the phase 3 study, titled "Efficacy Subgroup Analysis of Estetrol/Drospirenone for Pregnancy Prevention: US/Canadian Phase 3 Trial," contraceptive efficacy was evaluated during 13 consecutive 28-day cycles. Key findings include:

• The Pearl Index (PI) (95% confidence interval [CI]) among those 16-25 years old (n=748) and 26-35 years old (n=776) was 3.07 (1.68-5.14) and 2.29 (1.18-3.99), respectively.
• No association between contraceptive efficacy and BMI was observed, as the PIs calculated for participants with a BMI<30 kg/m² (n=1187) and BMI≥30 kg/m² (n=337) were 2.57 (1.57-3.97) and 2.94 (1.08-6.41), respectively.
• The PIs based on switchers (n=656) and starters (n=868) were 2.13 (1.02-3.92) and 3.12 (1.78-5.06), respectively.

In addition to efficacy, a predictable bleeding pattern is another key consideration for women and their healthcare providers. Bothersome breakthrough bleeding is a common side effect of hormonal contraception and can often lead to discontinuation of the contraception. Discontinuation due to side effects such as bleeding can increase the risk for unintended pregnancy, especially when a backup contraceptive method is not used.

"For women taking birth control, unscheduled bleeding is one of the main reasons cited for stopping or switching to an alternate contraceptive and an important consideration when working with a patient to find the birth control that works best for them," said Dr. Creinin. "The bleeding pattern seen with NEXTSTELLIS was regular and predictable for most women - with low rates of unscheduled bleeding even at cycle 1 - providing clinicians with another important option when patients are concerned about breakthrough bleeding."

In the phase 3 study, titled "Unscheduled bleeding and/or spotting episodes in a Phase 3 Clinical Trial of Estetrol/Drospirenone," bleeding patterns were recorded over 13 consecutive cycles and analyzed based on age, BMI and starters/switchers of hormonal contraceptives. Key findings include:

• Unscheduled bleeding and/or spotting episodes decreased in women aged 16-25 years old and 26-35 years old from cycle 1 (30% in both groups) to cycle 2 (21% and 23%, respectively) and was less than 20% from cycle 5, except for cycle 7 (20.8%) among 26-35 years old women. Most unscheduled bleeding was spotting.
• No remarkable differences of unscheduled bleeding and/or spotting episodes were observed in subjects with BMI<30kg/m² and BMI≥30 kg/m² (30% and 31% during the first cycle, decreased to 21% and 24% in cycle 2, respectively, and 18-14% and 24-18%, respectively, in subsequent cycles 6 through 13).
• Unscheduled bleeding and/or spotting decreased in starters from 35% in cycle 1 to 18% in cycle 5 and ranged between 21-18% thereafter. Switchers' unscheduled bleeding and/or spotting episodes decreased from 24% in cycle 1 to 17% in cycle 5 and ranged between 13-18% thereafter.

NEXTSTELLIS was approved by the U.S. Food and Drug Administration (FDA) on April 15, 2021, for the prevention of pregnancy and the company anticipates the commercial launch of NEXTSTELLIS by the end of June 2021.

Study design

The multicenter, open-label, phase 3 trial of NEXTSTELLIS enrolled 2,148 healthy participants, aged 16-50 years with a body mass index (BMI) ≤35 kg/m². In a subset of 1,674 participants, aged 16 to 35 years, the contraceptive efficacy and bleeding pattern of NEXTSTELLIS were evaluated.

During 13 consecutive 28-day cycles, Pearl Index (PI) was analyzed using at-risk cycles, defined as intercourse with no other birth control method used. Subjects completed a daily diary that included pill intake, other contraceptive methods used and sexual intercourse. Additional descriptive PI subgroup analyses were performed based on age, BMI and historical use of contraceptives (switchers, which included those with hormonal contraceptive use within past 3 months, and starters, women with no hormonal contraceptive use in the last 3 months or ever).

Subjects also recorded bleeding patterns in daily diaries over the 13 consecutive cycles. Unscheduled bleeding and/or spotting episodes were analyzed based on age, BMI, and starters/switchers of hormonal contraceptives.

About NEXTSTELLIS

NEXTSTELLIS is a novel, combined oral contraceptive pill containing 3 mg drospirenone (DRSP) and 14.2 mg estetrol (E4) indicated for use by females of reproductive age to prevent pregnancy. E4 is a naturally produced estrogen during pregnancy, which can now be made from a plant source. In two phase 3 clinical studies conducted in 3,725 women, NEXTSTELLIS was shown both safe and effective and met its primary efficacy endpoint of pregnancy prevention while also meeting a variety of secondary endpoints that demonstrated favorable cycle control, bleeding control, safety, and tolerability.

IMPORTANT SAFETY INFORMATION

The following ISI is based on the highlights section of the U.S. Prescribing Information for NEXTSTELLIS. These highlights do not include all the information needed to use NEXTSTELLIS safely and effectively. Please consult the full Prescribing Information for all labelled safety information for NEXTSTELLIS.

WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS
See full prescribing information for complete boxed warning.

• Females over 35 years old who smoke should not use NEXTSTELLIS
• Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use.

INDICATIONS AND USAGE

NEXTSTELLIS is a combination of drospirenone, a progestin, and estetrol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy.

Limitations of Use

NEXTSTELLIS may be less effective in females with a BMI ≥ 30 kg/m². In females with BMI ≥ 30 kg/m², decreasing effectiveness may be associated with increasing BMI.

CONTRAINDICATIONS

NEXTSTELLIS is contraindicated and should not be used in women with a high risk of arterial or venous thrombotic diseases; current or history of a hormonally-sensitive malignancy (e.g., breast cancer); hepatic adenoma; hepatocellular carcinoma; acute hepatitis or decompensated cirrhosis; co-administration with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir; abnormal uterine bleeding that has an undiagnosed etiology; renal impairment; adrenal insufficiency.

WARNINGS AND PRECAUTIONS

• Thromboembolic Disorders and Other Vascular Problems:
• Stop NEXTSTELLIS if a thrombotic or thromboembolic event occurs.  Start no earlier than 4 weeks after delivery. Consider all cardiovascular risk factors before initiating in any female, particularly in the presence of multiple risk factors.
• Hyperkalemia:   
  • Check serum potassium concentration during the first NEXTSTELLIS treatment cycle in females on long-term treatment with medications that may increase serum potassium concentration.
• Hypertension - Monitor blood pressure periodically and stop use if blood pressure rises significantly.
• Migraine – Discontinue if new, recurrent, persistent, or severe migraines occur. 
• Hormonally-Sensitive Malignancy - Discontinue NEXTSTELLIS if a hormonally-sensitive malignancy is diagnosed.
• Liver Disease-Withhold or permanently discontinue for persistent or significant elevation of liver enzymes. 
• Glucose Tolerance and Hypertriglyceridemia -Monitor glucose in females with prediabetes or diabetes.  Consider an alternate contraceptive method for females with hypertriglyceridemia.
• Gallbladder Disease and Cholestasis:  Consider discontinuing NEXTSTELLIS in females with symptomatic gallbladder or cholestatic disease. 
• Bleeding Irregularities and Amenorrhea: may cause irregular bleeding or amenorrhea.  Evaluate for other causes if symptoms persist.

ADVERSE REACTIONS

• The following most common adverse reactions occurred in ≥2% of women who received NEXTSTELLIS:  bleeding irregularities, mood disturbance, headache, breast symptoms, dysmenorrhea, acne, weight increased, and libido decreased.

To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS

• CYP3A Inducers: May lead to contraceptive failure and/or increase breakthrough bleeding. Avoid concomitant use. If concomitant use is unavoidable, use an alternative or back-up contraceptive method during co-administration and up to 28 days after discontinuation of the CYP3A inducer.
• See Full Prescribing Information for additional clinically significant drug interactions.

This is not a comprehensive list of safety information related to NEXTSTELLIS.

Please See Full Prescribing Information, including BOXED WARNING.

About Mayne Pharma

Mayne Pharma is focused on applying its track record of innovation and success in developing new oral drug delivery systems to commercialize branded and generic pharmaceuticals, offering patients better and more accessible medicines. The company has an extensive Women's Health portfolio focused on contraceptives, including its flagship birth control product, NEXTSTELLIS. Its parent company, Mayne Pharma Group Limited, is an ASX-listed specialty pharmaceutical company that also provides contract development and manufacturing services to more than 100 clients worldwide.

Mayne Pharma and Mayne Pharma Group Limited are based in Greenville, NC and Salisbury, Australia, respectively.

NEXTSTELLIS® is a registered trademark of a third party.

¹ In females with BMI ≥ 30 kg/m², decreasing effectiveness may be associated with increasing BMI.

CONTACT:
Karen Dombek
[email protected]

SOURCE Mayne Pharma