Dienogest; estradiol valerate - Generic Drug Details

What are the generic drug sources for dienogest; estradiol valerate and what is the scope of freedom to operate?

Dienogest; estradiol valerate is the generic ingredient in one branded drug marketed by Bayer Hlthcare and is included in one NDA. There are two patents protecting this compound and one Paragraph IV challenge. Additional information is available in the individual branded drug profile pages.

Dienogest; estradiol valerate has ninety patent family members in thirty-nine countries.

Two suppliers are listed for this compound. There is one tentative approval for this compound.

Summary for dienogest; estradiol valerate

International Patents:	90
US Patents:	2
Tradenames:	1
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	2
Clinical Trials:	14
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for dienogest; estradiol valerate
DailyMed Link:	dienogest; estradiol valerate at DailyMed

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for dienogest; estradiol valerate

Constraining patent/regulatory exclusivity:

8,071,577

Dosage:

TABLET;ORAL

^*The generic entry opportunity date is the latter of the last compound-claiming patent and the last regulatory exclusivity protection. Many factors can influence early or later generic entry. This date is provided as a rough estimate of generic entry potential and should not be used as an independent source.

Recent Clinical Trials for dienogest; estradiol valerate

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Laboratorios Andromaco S.A.	Phase 1
Suleymaniye Birth And Women's Health Education And Research Hospital	Phase 4
Kocaeli Derince Education and Research Hospital	Phase 4

See all dienogest; estradiol valerate clinical trials

Generic filers with tentative approvals for DIENOGEST; ESTRADIOL VALERATE

Applicant	Application No.	Strength	Dosage Form
		N/A,2MG,3MG,N/A,N/A;3MG,2MG,2MG,1MG,N/A	TABLET;ORAL

The 'tentative' approval signifies that the product meets all FDA standards for marketing, and, but for the patents / regulatory protections, it would approved.

Anatomical Therapeutic Chemical (ATC) Classes for dienogest; estradiol valerate

G03CA	Natural and semisynthetic estrogens, plain
G03C	ESTROGENS
G03	SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
G	Genito-urinary system and sex hormones

G03DB	Pregnadien derivatives
G03D	PROGESTOGENS
G03	SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
G	Genito-urinary system and sex hormones

Paragraph IV (Patent) Challenges for DIENOGEST; ESTRADIOL VALERATE

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
NATAZIA	Tablets	dienogest; estradiol valerate	3 mg;2 mg/2 mg; 2 mg/3 mg and 1 mg	022252	1	2010-10-22

US Patents and Regulatory Information for dienogest; estradiol valerate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Bayer Hlthcare	NATAZIA	dienogest; estradiol valerate	TABLET;ORAL	022252-001	May 6, 2010		RX	Yes	Yes	8,153,616
Bayer Hlthcare	NATAZIA	dienogest; estradiol valerate	TABLET;ORAL	022252-001	May 6, 2010		RX	Yes	Yes	8,071,577		Y

Expired US Patents for dienogest; estradiol valerate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Bayer Hlthcare	NATAZIA	dienogest; estradiol valerate	TABLET;ORAL	022252-001	May 6, 2010	6,133,251
Bayer Hlthcare	NATAZIA	dienogest; estradiol valerate	TABLET;ORAL	022252-001	May 6, 2010	6,884,793

International Patents for dienogest; estradiol valerate

Country	Patent Number	Title	Estimated Expiration
Germany	502006008853
Taiwan	200829255	Use of oestradiol in combination with dienogest for the oral treatment of dysfunctional uterine bleeding in conjunction with oral contraception
Malaysia	143669	MULTIPHASE PRODUCT FOR CONTRACEPTION BASED ON A NATURAL OESTROGEN
Eurasian Patent Organization	200601844	МНОГОФАЗНЫЙ ПРЕПАРАТ ДЛЯ КОНТРАЦЕПЦИИ НА ОСНОВЕ НАТУРАЛЬНОГО ЭСТРОГЕНА

Supplementary Protection Certificates for dienogest; estradiol valerate

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
0770388	SPC/GB09/026	United Kingdom		PRODUCT NAME: ESTRADIOL AND COMBINATIONS OF ESTRADIOL AND DIENOGEST, PREFERABLY ESTRADIOL VALERATE AND COMBINATIONS OF ESTRADIOL VALERATE AND DIENOGEST; REGISTERED: BE BE 327792 20081103; UK PL 00010/0576-0001 20081208
0770388	09C0018	France		PRODUCT NAME: ESTRADIOL VALERATE; DIENOGEST; NAT. REGISTRATION NO/DATE: NL35170 20081210; FIRST REGISTRATION: BE327792 20081103
0770388	9/2009	Austria		PRODUCT NAME: KOMBINATION AUS ESTRADIOLVALERAT UND DIENOGEST; NAT. REGISTRATION NO/DATE: 1-28003 20090203; FIRST REGISTRATION: BE BE 327792 20081103
0770388	2009/012	Ireland		PRODUCT NAME: QLAIRA-ESTRADIOL VALERATE/DIENOGEST; NAT REGISTRATION NO/DATE: PA1410/58/1 20090109; FIRST REGISTRATION NO/DATE: BE327792 20081103

Market Dynamics and Financial Trajectory for Dienogest; Estradiol Valerate

Introduction

Dienogest and estradiol valerate, combined in the oral contraceptive known as Natazia or Qlaira, represent a significant advancement in the field of reproductive health. This 4-phasic oral contraceptive has been approved for the prevention of pregnancy and the treatment of heavy menstrual bleeding. Here, we will delve into the market dynamics and financial trajectory of this drug.

Regulatory Approval and Market Entry

The FDA approved the combination of estradiol valerate and dienogest in 2010 for the prevention of pregnancy and the treatment of heavy menstrual bleeding in women of childbearing age[1][2][4].

Approval Process

The approval was based on extensive clinical trials, including two pivotal Phase 3 studies conducted in Europe and the US/Canada. These trials demonstrated the efficacy and safety of the drug, with a favorable risk-benefit assessment comparable to other combination oral contraceptives[1][2].

Market Positioning

Unique Selling Points

• 4-Phasic Regimen: Unlike many monophasic or biphasic oral contraceptives, the 4-phasic regimen of estradiol valerate and dienogest offers a dynamic dosing schedule that helps in maintaining cycle control and reducing menstrual bleeding[2][3].
• Natural Estrogen: The use of estradiol valerate, a natural estrogen, is a significant differentiation from other oral contraceptives that often use ethinyl estradiol, which can have more pronounced effects on hepatic enzymes[3].

Target Market

The primary target market for this drug is women of reproductive age seeking effective contraception and those experiencing heavy menstrual bleeding. The drug is particularly recommended for women who are intolerant of other combination oral contraceptives[2].

Clinical Efficacy and Safety

Contraceptive Efficacy

The Pearl Index, a measure of contraceptive efficacy, ranged from 0.40 to 1.64 in clinical trials, indicating that the drug is as effective as other combination oral contraceptives[2][3].

Safety Profile

The safety profile of estradiol valerate and dienogest is similar to that of other oral contraceptives, with common adverse effects including headache, metrorrhagia, breast tenderness, nausea or vomiting, acne, and weight gain[2][4].

Market Competition

Existing Oral Contraceptives

The market for oral contraceptives is highly competitive, with numerous monophasic, biphasic, and triphasic options available. However, the unique 4-phasic regimen and the use of natural estrogen in estradiol valerate and dienogest differentiate this product from competitors like Miranova, Triquilar, and Valette[1][2].

Financial Performance

Revenue Generation

Since its approval, Natazia has generated significant revenue for Bayer HealthCare Pharmaceuticals Inc. The drug's unique features and its approval for both contraception and heavy menstrual bleeding have contributed to its market success.

Market Share

While exact market share figures are not publicly disclosed, the drug has carved out a niche for itself in the oral contraceptive market. Its efficacy and safety profile, combined with its unique dosing regimen, have attracted a loyal patient base.

Pricing and Accessibility

Pricing Strategy

The pricing of Natazia is competitive with other oral contraceptives on the market. However, the cost can vary based on insurance coverage and geographic location. Generally, it is priced to be accessible to a wide range of patients seeking effective contraception and treatment for heavy menstrual bleeding[4][5].

Insurance Coverage

In many countries, Natazia is covered by health insurance plans, making it more accessible to patients. This coverage is crucial for maintaining market share and ensuring patient adherence to the treatment regimen.

Future Outlook

Expanding Indications

There is potential for expanding the indications of estradiol valerate and dienogest to other reproductive health issues, such as polycystic ovary syndrome (PCOS) or endometriosis, based on ongoing research and clinical trials.

Generic Competition

As patents expire, generic versions of the drug may enter the market, potentially impacting the financial trajectory of the branded product. However, the unique formulation and dosing regimen of Natazia may help it maintain a competitive edge even in the face of generic competition.

Key Takeaways

• Regulatory Approval: Approved by the FDA in 2010 for contraception and heavy menstrual bleeding.
• Unique Formulation: 4-phasic regimen with natural estrogen (estradiol valerate) and progestin (dienogest).
• Target Market: Women of reproductive age seeking effective contraception and those with heavy menstrual bleeding.
• Clinical Efficacy: Comparable to other combination oral contraceptives with a favorable safety profile.
• Market Competition: Differentiated by its 4-phasic regimen and natural estrogen, competing in a crowded oral contraceptive market.
• Financial Performance: Significant revenue generation with a competitive pricing strategy and insurance coverage.

FAQs

What are the primary indications for estradiol valerate and dienogest?

The primary indications are the prevention of pregnancy and the treatment of heavy menstrual bleeding in women of childbearing age.

How does the 4-phasic regimen of estradiol valerate and dienogest work?

The regimen involves different doses of estradiol valerate and dienogest over a 28-day cycle, helping to maintain cycle control and reduce menstrual bleeding.

What are the common adverse effects of estradiol valerate and dienogest?

Common adverse effects include headache, metrorrhagia, breast tenderness, nausea or vomiting, acne, and weight gain.

Is estradiol valerate and dienogest covered by health insurance?

Yes, in many countries, Natazia is covered by health insurance plans, making it more accessible to patients.

Can estradiol valerate and dienogest be used by women who are breastfeeding?

There are no adequate studies on the use of this medication during breastfeeding, so it is recommended to weigh the potential benefits against the potential risks before taking this medication while breastfeeding[4].

Sources

1. FDA: N22252 Natazia Clinical PREA - FDA.
2. PubMed: Estradiol valerate/dienogest: a novel oral contraceptive.
3. Elsevier: Evaluation of a new estradiol oral contraceptive: Estradiol valerate ...
4. Mayo Clinic: Estradiol and dienogest (oral route).
5. Cleveland Clinic: Dienogest; Estradiol valerate oral tablets.