What’s NEXT in birth control?

NEXTSTELLIS product logo with generic

NOW AVAILABLE

Your patients care about the estrogen in their birth control. Now you can offer them NEXTSTELLIS®—the first combined oral contraceptive in 50 years to contain a newly approved estrogen1-3

A NEW TYPE OF ESTROGEN
Introducing estetrol (E4)—the estrogen that makes NEXTSTELLIS unique

Native

Estetrol is a native estrogen that:

  • Circulates between the mother and fetus at high levels during human pregnancy4
  • Is produced from a plant source5
Selective

Estetrol has intrinsic tissue-selective properties:

  • Estetrol is selective for nuclear estrogen receptors and is the first estrogen to be described as a NEST: a Native Estrogen with Selective actions in Tissues6

HOW NEXTSTELLIS WORKS
Pairing the selective activity of estetrol (E4) with the proven progestin drospirenone (DRSP)1,7

Estetrol is selective for tissues that depend predominantly on nuclear estrogen receptors6

Tissues in the body respond differently to estrogen based on their dependence on nuclear or membrane receptor signaling.8,9

  • Other contraceptive estrogens bind widely to 2 main types of estrogen receptor alpha (ERα)—nuclear ERα and membrane ERα8,10,11
Nuclear icon

TISSUE SELECTIVITY

Estetrol activates nuclear ERα but antagonizes membrane ERα. This gives estetrol selective effects in different tissue types.6

Tissue types predominantly dependent on membrane or nuclear ERα signaling

NUCLEAR DEPENDENT

MEMBRANE DEPENDENT

Breast12 Stimulates growth

Membrane icon

Vascular System12 Prevents plaque accumulation

Nuclear icon

Liver8,13 Impacts liver lipid metabolism

Nuclear icon
Membrane icon

Bone13,14 Maintains bone mineral density

Nuclear icon
Membrane icon

Vascular system12 Repairs and maintains tissue/Regulates vascular tone

Membrane icon

Uterus12 Supports tissue maintenance

Nuclear icon

Vagina15 Supports tissue maintenance

Nuclear icon

Why estetrol?

More than 99% of combined contraceptives use ethinyl estradiol (EE)—a synthetic, modified form of estradiol (E2).10,11,16

What makes estetrol different?

  • First unmodified estrogen available in a COC1
  • Selective for tissues that depend predominantly on nuclear estrogen receptors6
  • Long half-life (24-28 hours)17,18
  • Minimal metabolism by the liver4
Chemical structures of estetrol and ethinyl estradiol

Why DRSP?

DRSP was selected as the progestin component of NEXTSTELLIS based on results of Phase II studies evaluating estetrol/DRSP compared with estetrol/LNG.19

What makes DRSP different?

  • Similar activity in the body as native progesterone7
  • Anti-mineralocorticoid properties20
  • Anti-androgenic properties20
  • Long half-life (~30 hours)25

Progestin Comparison20-25

Comparison table shows how various progestins relate to anti-estrogenic, anti-androgenic, and anti-mineralocorticoidDRSP=drospirenone; LNG=levonorgestrel; NET=norethindrone; NGM=norgestimate; P=natural progesterone.

CLINICAL TRIAL PROGRAM
The efficacy patients want from a COC—now with the selective effects of estetrol (E4)1

Overview of the NEXTSTELLIS clinical trial program

NEXTSTELLIS demonstrated efficacy and safety in a robust clinical trial program. The Phase III patient population included women ages 16-50 years and a large BMI cohort (23% of patients had BMI 30-35 kg/m2). In Phase II studies, NEXTSTELLIS was compared head-to-head against 2 standard-of-care birth control pills—Yaz® (DRSP/EE) and Nordette® (LNG/EE).1,7,26-28

NEXTSTELLIS Clinical Trials: Phase II included 681 patients in 4 trials. Phase III included 3632 in 2 trials

Click below to learn more about the trial design and end points in the:


Phase II trial program

Dose-finding studies

In 2 Phase II dose-finding studies, 2 progestins (DRSP and LNG) were evaluated in combination with estetrol to determine29,30:

  • Minimum effective dose of estetrol
  • Most complementary progestin

End points included29,30:

  • Ovulation inhibition
  • Bleeding patterns
  • Effect on liver parameters
  • Effect on sex hormone-binding globulin (SHBG)

Safety studies

In 2 Phase II safety studies, NEXTSTELLIS was studied head-to-head against 2 standard-of-care COCs7,27*:

  • Yaz® (20 mcg EE/3 mg DRSP)
  • Nordette®† (30 mcg EE/150 mcg LNG)

End points included7,27:

  • Hemostasis parameters
  • Endocrine parameters, as well as SHBG
  • Lipid and carbohydrate metabolism parameters
  • Ovulation inhibition
*Both Phase II studies included Yaz® (EE/DRSP) as a comparator; only 1 (C201) included Nordette® (EE/LNG).
European trade name is Melleva®.28

Phase III trial program

Patient demographics reflect a real-world range in age, ethnicity, weight, and contraceptive history1,26,31

Phase III clinical trials included 3632 women from North America and the European Union aged 16 to 50 years

The 2 Phase III trials of NEXTSTELLIS studied 3632 women (ages 16-50 years). The efficacy population in the North American trial was 1524 (ages 16-35 years), and in the EU/Russian study, it was 1313 (ages 18-35 years). Women were studied over 12 months for 13 menstrual cycles, totaling 26,455 at-risk cycles.1,26,31


Patient demographics

CONTRACEPTIVE HISTORY26

  • Switching: 42%
  • Starting: 58%
    • Naive users: 17%

ETHNICITY26

  • Hispanic or Latino: 26%
  • Not Hispanic or Latino: 74%

WEIGHT26

  • 23% BMI with 30-35 kg/m2
    (mean BMI: 25.8 kg/m2)

RACE1

  • White: 70%
  • Black: 20%
  • Asian: 5%
  • American Indian or Alaskan Native: 1%
  • Native Hawaiian or Pacific Islander: 0.4%
  • Other: 4%

PHASE III DATA
Results from a large and inclusive trial program

Key clinical endpoints from the North American Phase III trial

98%

Contraceptive efficacy

NEXTSTELLIS was effective in preventing pregnancy (Pearl index: 2.65).1,26

BMI ≥30

Effective across body sizes

The high BMI subgroup (BMI 30-35 kg/m2) had a Pearl index of 2.94.1*

*NEXTSTELLIS may be less effective in women with BMI ≥30 kg/m2. In women with BMI ≥30 kg/m2, decreasing effectiveness may be associated with increasing BMI.1

In the Phase III study, bleeding patterns were similar to a natural, predictable menstrual cycle26

NEXTSTELLIS, with its 24/4 monophasic regimen, delivers a predictable bleeding pattern1,26

Scheduled
Bleeding

85%

On average, 85% of women experienced regular withdrawal bleeding (range: 82%-87% across cycles).26

Unscheduled
Bleeding

<2%

<2% of patients experienced unscheduled bleeding-only episodes after cycle 2.26

Average
Duration

<1 day

<1 day of any unscheduled spotting or bleeding on average per cycle after cycle 1.26

Treatment
Discontinuation

2.8%

2.8% of patients withdrew from treatment due to bleeding irregularities.1


Minimal unscheduled spotting or bleeding in the Phase III study even at cycle 1

The majority of patients who reported unscheduled spotting and/or bleeding experienced spotting only26

  • Spotting was defined as minimal bleeding that did not require the use of any sanitary protection (including pantyliners)26
  • 30% of patients had unscheduled spotting or bleeding at cycle 1, decreased to 22% at cycle 2, and remained <20% after cycle 426
  • The average duration of bleeding or spotting per cycle was <1 day after cycle 126

Women reporting unscheduled spotting, mixed bleeding/spotting, or bleeding in the North Americans phase III Trial (cycles 1-12)26

Over 12 cycle periods, women report incidents of bleeding, mixed bleeding/spotting, and spotting only
  • Bleeding-only episodes occurred in <2% of patients over all 12 cycles studied26
  • The bleeding profile was similar across patient subgroups (BMI ≥30 kg/m2, starters, switchers)26

Proven tolerability and safety in 2 Phase III studies with 3632 patients ages 16-50 years1

Most commonly reported adverse reactions (≥2% of patients) in the pooled Phase III trial results1

ADVERSE REACTIONS IN WOMEN RECEIVING NEXTSTELLIS

Preferred term Participants with adverse reactions:
US/Canadian Phase III trial (n, %) (N=2073)
Participants with adverse reactions:
2 Phase III trials (n, %) (N=3632)
Any adverse reaction1205 (58.1)2126 (58.5)
Mood disturbance226 (10.9)329 (9.1)
Bleeding irregularities201 (9.7)393 (10.8)
Breast symptoms110 (5.3)197 (5.4)
Headache100 (4.8)227 (6.3)
Dysmenorrhea84 (4.1)133 (3.7)
Weight increased68 (3.3)108 (3.0)
Acne66 (3.2)136 (3.7)
Libido decreased/lost27 (1.3)72 (2.0)
  • Any Adverse Reaction equals any Adverse Event ≥2%1
  • Adverse Events include non-drug and drug-related AEs32

Most common adverse reactions

  • The most common adverse reactions (≥2%) in the studies were bleeding irregularities, mood disturbance, headache, breast symptoms, dysmenorrhea, acne, increased weight, and decreased libido1

Serious adverse reactions

  • Serious adverse reactions included depression (n=36), venous thromboembolism (VTE; n=1), and migraine (6 women [0.17%] discontinued study participation due to new onset of migraine with aura; 2 women [0.05%] discontinued due to severe migraine)1

NEXTSTELLIS demonstrated safety and was well-tolerated

NEXTSTELLIS VTE RATE

The rate of VTE in women taking NEXTSTELLIS was 3.66 per 10,000 women-years.33 One VTE occurred in the EU/Russian trial; there were none reported in the North American trial.26,31

Likelihood of VTE in women1

Incidence of VTEs in non-pregnant, non-COC users ranges from 1-5, from 3-9 in COC users, 5-20 in pregnancy, and 50-64 postpartum (up to 12 weeks)Incidence of VTEs in non-pregnant, non-COC users ranges from 1-5, from 3-9 in COC users, 5-20 in pregnancy, and 50-64 postpartum (up to 12 weeks)
*Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy is 9 months, the rate is 7 to 27 per 10,000 WY.

Tolerability profile

NEXTSTELLIS demonstrated low rates of the side effects often associated with COCs, including acne, breast symptoms (e.g., pain, tenderness), and libido changes.1

Bar chart showing side effect rates of patients on Nextstellis: 3.7% acne, 5.4% breast tenderness, 2% libido change

Effect on weight

On average, women taking NEXTSTELLIS experienced less than a 1.1-lb weight increase after 6 treatment cycles in the North American study.26

WEIGHT CHANGE <1.1 lb (N=1864)


In the Phase III study, NEXTSTELLIS had low impact on metabolic parameters26

Measures of lipid and glucose metabolism were compared at baseline, cycle 7, and cycle 14

Lipid Metabolism

Neutral effect icon
CHOLESTEROL

Minimal change from baseline in cholesterol (HDL and LDL)

Neutral effect icon
TRIGLYCERIDES

Minimal change from baseline in glucose

Glucose Metabolism

Neutral effect icon
GLUCOSE

Minimal change from baseline in glucose

Neutral effect icon
GLYCATED HEMOGLOBIN

No change from baseline in glycated hemoglobin

Women who had diabetes mellitus and vascular involvement, diabetes mellitus of >20 years' duration, or dyslipoproteinemia requiring active treatment with anti-lipidemic agents were excluded from the study.

DOSING & ADMINISTRATION
Getting started on NEXTSTELLIS

The NEXTSTELLIS 24/4 monophasic regimen can fit into your patients’ reproductive health journey, wherever they are right now1

NEXTSTELLIS Dosing Packaging

To prevent pregnancy, patients should be instructed to take NEXTSTELLIS exactly as prescribed: 1 tablet daily for 28 consecutive days; 1 pink (active) tablet daily during the first 24 days and 1 white (inert) tablet daily during the following 4 days. To achieve maximum contraceptive effectiveness, take 1 tablet every day at about the same time each day. For patient instructions for starting NEXTSTELLIS and for missed pills, see the full Prescribing Information.1


A fit for any phase of reproductive life

Whether she's starting a contraceptive for the first time, wants a new and different contraceptive option, or considers her family complete, consider how the one-of-a-kind formulation of NEXTSTELLIS may meet her needs.

Silhouette of woman with hands on her hips

“Starter”

Using contraception for the first time

Silhouette of woman with bag over her shoulder

“Switcher”

Wants to switch contraceptive methods

Silhouette of woman holding hands with child

“Spacer”

Not yet ready to expand her family

Silhouette of woman standing with arms crossed

“Perimenopausal”

Later in her reproductive life

  • Effective pregnancy prevention with a 24/4 monophasic regimen1
  • Long half-life18
  • Low rates of side effects (weight gain, acne, breast symptoms, decreased libido)
  • Low impact on metabolic parameters26
  • Native, selective estrogen1
  • Favorable bleeding patterns, including in starter subgroup26
  • Only COC without estradiol-based estrogen10,11
  • Easily return to ovulation upon stopping27

HCP RESOURCES
NEXTSTELLIS Savings Program

Covered, eligible patients may pay as little as $25*

With the NEXTSTELLIS Savings Program, eligible patients may pay as little as $25* for a 1-month or 3-month prescription fill. Consider reducing your patients’ visits to the pharmacy and write a 3-month prescription.

NEXTSTELLIS Copay Card*Depending on insurance coverage, eligible patients may pay as little as $25 for each of up to 12 one-month NEXTSTELLIS prescription fills OR each of up to 4 three-month NEXTSTELLIS prescription fills. Check with pharmacist for copay discount. Maximum savings limits apply; patient out-of-pocket expense will vary. Offer not valid for patients enrolled in Medicare, Medicaid, or other federal or state healthcare programs. Please see Program Terms, Conditions, and Eligibility Criteria here.

2 ways to save

You can request preactivated Savings Cards from a Mayne Pharma representative.

Contact a rep

Your patients can sign up for the Savings Card online.

Patient sign-up

For questions about this program, please call
1-347-442-7919.


Cover My Meds LogoCoverMyMeds® is a registered trademark of CoverMyMeds LLC.

CoverMyMeds helps patients get the medication they need by addressing access challenges from the point-of-prescribing to the pharmacy counter. Prior authorization support is available for NEXTSTELLIS through CoverMyMeds by signing up for a free account.

Create a free account

NEXTSTELLIS is also available through an online, white-glove pharmacy service

Blink Pharmacy Plus Logo

An alternative to retail pharmacies, Blink Pharmacy Plus is an online pharmacy that offers savings on prescription medications including NEXTSTELLIS.

  • Free home delivery service
  • No copay card is needed
  • Cash payment option available through Blink Pharmacy Plus
  • Available nationwide
  • Send prescriptions for any medication to Blink

Download the informational brochure here:

Download Blink info

REQUEST A REP
Contact a Mayne Pharma representative

Submit a request for more information from a Mayne Pharma representative. Receive information about product availability, our sampling program, and patient support resources.

*Required fields.

IMPORTANT SAFETY INFORMATION

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.

IMPORTANT SAFETY INFORMATION FOR NEXTSTELLIS® (drospirenone and estetrol tablets 3 mg/14.2 mg)

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use NEXTSTELLIS safely and effectively. See full prescribing information for NEXTSTELLIS.

NEXTSTELLIS (drospirenone and estetrol tablets), for oral use
Initial U.S. Approval: 2021

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.

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.

DOSAGE AND ADMINISTRATION

  • Take one tablet by mouth at the same time every day.
  • Take tablets in the order directed on the blister pack.

DOSAGE FORMS AND STRENGTHS

NEXTSTELLIS consists of 28 tablets in the following order:

  • 24 pink active tablets each containing drospirenone 3 mg and estetrol 14.2 mg
  • 4 white inert tablets

CONTRAINDICATIONS

  • 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

Most common adverse reactions (≥2%): bleeding irregularities, mood disturbance, headache, breast symptoms, dysmenorrhea, acne, weight increased, and libido decreased

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.

USE IN SPECIFIC POPULATIONS

  • Pregnancy: Discontinue if pregnancy occurs.
  • Lactation: Advise postpartum females that NEXTSTELLIS can decrease milk production.

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

See PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

AE=adverse event; BMI=body mass index; COC=combined oral contraceptive; EU=European Union; HDL=high-density lipoprotein; LDL=low-density lipoprotein; LNG=levonorgestrel.

References

1. NEXTSTELLIS [package insert]. Greenville, NC: Mayne Pharma; April 2021. 2. Szarewski A, Mansour D, Shulman LP. 50 years of “The Pill”: celebrating a golden anniversary. J Fam Plann Reprod Health Care. 2010;36(4):231-238. 3. Hall KS, Trussell J. Types of combined oral contraceptives used by U.S. women. Contraception. 2012; 86(6):659-665. 4. Coelingh Bennink HJT, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11(suppl 1):47-58. 5. New data on NEXTSTELLIS presented at ISSWSH conference. News release. Mayne Pharma. Accessed May 21, 2021. https://www.maynepharma.com/investor-relations/company-announcements 6. Foidart JM, Gaspard U, Pequeux C, et al. Unique vascular benefits of estetrol, a native fetal estrogen with specific actions in tissues (NEST). In: Brinton RD, Genazzani AR, Simoncini T, Stevenson JC, eds. Sex Steroids’ Effects on Brain, Heart and Vessels Volume 6: Frontiers in Gynecological Endocrinology. New York, NY: Springer International Publishing; 2019:169‐195. 7. Data on file. Clinical study report MIT‐Es0001‐C201. Mayne Pharma US. Greenville, NC. 8. Arnal JF, Lenfant F, Metivier R, et al. Membrane and nuclear estrogen receptor alpha actions: from tissue specificity to medical implications. Physiol Rev. 2017;97(3):1045-1087. 9. Moggs JG, Orphanides G. Estrogen receptors: orchestrators of pleiotropic cellular responses. EMBO Rep. 2001;2(9):775-781. 10. Stanczyk FZ, Archer DF, Bhavnani BR. Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment. Contraception. 2013;87(6):706-727. 11. Food and Drug Administration. FDA label database. Accessed May 21, 2021. https://nctr-crs.fda.gov/fdalabel/ui/search 12. Abot A, Fontaine C, Buscato M, et al. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014;6(10):1328-1346. 13. Ascenzi P, Bocedi A, Marino M. Structure-function relationship of estrogen receptor alpha and beta: impact on human health. Mol Aspects Med. 2006;27(4):299-402. 14. Coelingh Bennink HJT, Heegaard AM, Visser M, Holinka CF, Christiansen C. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric. 2008;11(suppl 1):2-14. 15. Benoit T, Valera MC, Fontaine C, et al. Estetrol, a fetal selective estrogen receptor modulator, acts on the vagina of mice through nuclear estrogen receptor α activation. Am J Pathol. 2017;187(11):2499-2507. 16. Shoham Z, Kopernik G. Tools for making correct decisions regarding hormone therapy. Part I: background and drugs. Fertil Steril. 2004;81(6):1447-1457. 17. Data on file. Clinical study report MIT‐Es0001‐C103. Mayne Pharma US. Greenville, NC. 18. Visser M, Holinka CF, Coelingh Bennink HJT. First human exposure to exogenous single-dose oral estetrol in early postmenopausal women. Climacteric. 2008;11(suppl 1):31-40. 19. Apter, D, Zimmerman Y, Beekman L, et al. Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results from a phase II, randomised, dose-finding study (FIESTA). Contraception. 2016;94(4):366-373. 20. Regidor PA, Schindler A. Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone. Oncotarget. 2017;8(47):83334-83342. 21. Levy T, Yairi Y, Bar-Hava I, et al. Pharmacokinetics of the progesterone-containing vaginal tablet and its use in assisted reproduction. Steroids. 2000;65(10-11):645-649. 22. Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005;8(suppl 1):3-63. 23. Ortho Tri-Cyclen [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc; October 2013. 24. Aygestin [package insert]. Pomona, NY: Duramed Pharmaceuticals Inc; July 2007. 25. Blode H, Kowal K, Roth K, Reif S. Pharmacokinetics of drospirenone and ethinyl estradiol in Caucasian and Japanese women. Eur J Contracept Reprod Health Care. 2012;17(4):284-297. 26. Data on file. Clinical study report MIT‐Es0001‐C302. Mayne Pharma US. Greenville, NC. 27. Data on file. Clinical study report MIT‐Es0001‐C202. Mayne Pharma US. Greenville, NC. 28. Food and Drug Administration. Prescription and over-the-counter drug product list: additions/deletions for prescription drug product list. August 2015. Accessed May 21, 2021. https://www.fda.gov/media/93516/download 29. Data on file. Clinical study report ES-C01/PR3095. Mayne Pharma US. Greenville, NC. 30. Data on file. Clinical study report ES-C02. Mayne Pharma US. Greenville, NC. 31. Data on file. Clinical study report MIT‐Es0001‐C301. Mayne Pharma US. Greenville, NC. 32. Electronic Code of Federal Regulations. IND safety reporting. 21 CFR §312.32. Accessed May 21, 2021. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.32 33. Data on file. NEXTSTELLIS New Drug Application, Module 2.5: Clinical Overview. Mayne Pharma US. Greenville, NC.