PREMPHASE (PREMARIN;CYCRIN 14/14) Drug Patent Profile

When do Premphase (premarin;cycrin 14/14) patents expire, and what generic alternatives are available?

Premphase (premarin;cycrin 14/14) is a drug marketed by Wyeth Pharms Inc and is included in one NDA.

The generic ingredient in PREMPHASE (PREMARIN;CYCRIN 14/14) is estrogens, conjugated; medroxyprogesterone acetate. There are three drug master file entries for this compound. One supplier is listed for this compound. Additional details are available on the estrogens, conjugated; medroxyprogesterone acetate profile page.

Summary for PREMPHASE (PREMARIN;CYCRIN 14/14)

US Patents:	0
Applicants:	1
NDAs:	1
Raw Ingredient (Bulk) Api Vendors:	71
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for PREMPHASE (PREMARIN;CYCRIN 14/14)
DailyMed Link:	PREMPHASE (PREMARIN;CYCRIN 14/14) at DailyMed

US Patents and Regulatory Information for PREMPHASE (PREMARIN;CYCRIN 14/14)

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Wyeth Pharms Inc	PREMPHASE (PREMARIN;CYCRIN 14/14)	estrogens, conjugated; medroxyprogesterone acetate	TABLET;ORAL-28	020303-002	Dec 30, 1994		DISCN	No	No

Expired US Patents for PREMPHASE (PREMARIN;CYCRIN 14/14)

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Wyeth Pharms Inc	PREMPHASE (PREMARIN;CYCRIN 14/14)	estrogens, conjugated; medroxyprogesterone acetate	TABLET;ORAL-28	020303-002	Dec 30, 1994	5,210,081

International Patents for PREMPHASE (PREMARIN;CYCRIN 14/14)

See the table below for patents covering PREMPHASE (PREMARIN;CYCRIN 14/14) around the world.

Country	Patent Number	Title	Estimated Expiration
Australia	677181
Greece	3029620
Mexico	9203720	METODO PARA EL TRATAMIENTO DE DESORDENES PERIMENOPAUSALES, MENOPAUSALES Y POSTMENOPAUSALES COMPOSICIONES Y UN PAQUETE DE MULTIPLES PREPARACIONES PARA ESTE METODO.
South Korea	100256861
Spain	2274555

Supplementary Protection Certificates for PREMPHASE (PREMARIN;CYCRIN 14/14)

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
0136011	2000C/027	Belgium		PRODUCT NAME: ETHINYLESTRADIOLUM / NORETHISTERONI ACETAS; NAT. REGISTRATION NO/DATE: 19 IS 106 F3 20000911; FIRST REGISTRATION: NL RVG 23909 19991124
0136011	91096	Luxembourg		91096, EXPIRES: 20090802
0136011	C00136011/03	Switzerland		PRODUCT NMAE: ESTRADIOL UND MEDROXYPROGESTERONACETAT; REGISTRATION NO/DATE: IKS 55288 20000417
0136011	SPC/GB00/025	United Kingdom		SPC/GB00/025: 20040802, EXPIRES: 20090801
0136011	SPC/GB97/032	United Kingdom		SPC/GB97/032: 20040802, EXPIRES: 20090801

Market Dynamics and Financial Trajectory for PREMPHASE (PREMARIN; CYCLIN 14/14)

Introduction

PREMPHASE, a combination of conjugated estrogens (CE) and medroxyprogesterone acetate (MPA), is a hormone therapy used to treat moderate to severe menopausal symptoms in women with a uterus. This article delves into the market dynamics and financial trajectory of PREMPHASE, particularly in the context of significant events and changes in the hormone therapy market.

Historical Context and Market Impact

The publication of the Women's Health Initiative (WHI) Estrogen Plus Progestin (E+P) study in July 2002 had a profound impact on the hormone therapy market, including PREMPHASE. The study highlighted potential health risks associated with hormone therapy, leading to a significant decline in prescriptions and promotional spending for these products[1].

Immediate Post-WHI E+P Report

Following the WHI E+P report, there was a 32% decrease in hormone therapy prescriptions within nine months. This decline was most marked for standard-dose Prempro, which saw a 64% decrease in prescriptions between Q2 of 2002 and Q1 of 2003. PREMPHASE, being another product in the same therapeutic class, also experienced a decline, although less severe than Prempro. The promotional spending for hormone therapies decreased by 82% from Q2 of 2002 to Q4 of 2003, with direct-to-consumer advertising ceasing entirely for standard-dose formulations[1].

Product Formulations and Adjustments

PREMPHASE is available in two separate tablets: a maroon tablet containing 0.625 mg of conjugated estrogens (CE) taken daily on days 1 through 14, and a light-blue tablet containing 0.625 mg CE plus 5 mg MPA taken on days 15 through 28[4][5].

Lower-Dose Formulations

In response to the WHI E+P findings, pharmaceutical companies began promoting lower-dose formulations of hormone therapies. For PREMPHASE and similar products, this shift included introducing lower-dose versions, such as PREMPRO 0.3 mg/1.5 mg and 0.45 mg/1.5 mg. These lower-dose formulations saw modest increases in prescriptions and promotional spending, indicating a strategic adjustment by manufacturers to mitigate the negative impact of the WHI E+P report[1].

Clinical Studies and Efficacy

Clinical studies have demonstrated the efficacy of PREMPHASE in treating menopausal symptoms. For example, studies have shown that PREMPRO (a similar formulation) significantly reduces the frequency and severity of hot flashes and other vasomotor symptoms compared to placebo. Additionally, these studies highlighted the reduced risk of endometrial hyperplasia when using combination therapy like PREMPHASE[3][5].

Adverse Reactions and Safety Considerations

While PREMPHASE is effective, it is not without risks. Common adverse reactions include abdominal pain, asthenia, back pain, headache, and others. The therapy also carries warnings for malignant neoplasms and other serious health conditions, which must be carefully considered by healthcare providers[5].

Market Competition and New Entrants

The market for menopausal treatments has seen the introduction of new products, such as Imvexxy and Annovera from TherapeuticsMD. These products target similar indications, including vulvar and vaginal atrophy, and have been gaining traction with modest commercial success. The competition from these new entrants has likely influenced the market dynamics for established products like PREMPHASE[2].

Financial Trajectory

The financial trajectory of PREMPHASE has been significantly influenced by the WHI E+P report and subsequent market adjustments.

Decline in Revenue

The immediate post-WHI E+P period saw a substantial decline in revenue due to reduced prescriptions and promotional spending. The total number of prescriptions for hormone therapy, including PREMPHASE, declined from 22.4 million in Q2 of 2002 to 12.7 million in Q4 of 2003, a 43% decline[1].

Recovery and Strategic Adjustments

Over time, manufacturers have adapted by promoting lower-dose formulations and other therapeutic options. This strategy has led to a modest recovery in prescriptions and revenue. For instance, the initiation of promotional spending on lower-dose estrogen formulations corresponded with increased prescriptions for these newer agents[1].

Current Market Status

As of recent years, the market for hormone therapies, including PREMPHASE, has stabilized to some extent. The focus on lower-dose formulations and targeted therapeutic approaches has helped in regaining some market share. However, the landscape remains competitive with new products and ongoing safety concerns.

Key Takeaways

• The WHI E+P report significantly impacted the market for hormone therapies, including PREMPHASE.
• Lower-dose formulations have been a key strategy in recovering market share.
• Clinical studies support the efficacy of PREMPHASE in treating menopausal symptoms.
• The market is competitive with new entrants targeting similar indications.
• Financial trajectory has been marked by an initial decline followed by a modest recovery.

FAQs

What was the impact of the WHI E+P report on PREMPHASE prescriptions?

The WHI E+P report led to a significant decline in hormone therapy prescriptions, including PREMPHASE, with a 32% decrease within nine months of the report's publication.

How have manufacturers adjusted their strategies for PREMPHASE post-WHI E+P?

Manufacturers have shifted focus to promoting lower-dose formulations of hormone therapies, which has led to modest increases in prescriptions and promotional spending.

What are the common adverse reactions associated with PREMPHASE?

Common adverse reactions include abdominal pain, asthenia, back pain, headache, and others. Serious health conditions such as malignant neoplasms are also potential risks.

How has the introduction of new products affected the market for PREMPHASE?

New products like Imvexxy and Annovera have entered the market, targeting similar indications and influencing the competitive landscape for established products like PREMPHASE.

What is the current financial status of PREMPHASE in the market?

The financial trajectory of PREMPHASE has stabilized to some extent, with a focus on lower-dose formulations helping to recover some market share, although the market remains competitive.

Sources

1. JAMA Network: Promotion and Prescribing of Hormone Therapy After Report of the Women's Health Initiative Estrogen Plus Progestin Trial.
2. TherapeuticsMD Inc: Oppenheimer NDR_TXMD Final 3.
3. Pfizer Medical Information: PREMPRO® AND PREMPHASE® Clinical Studies.
4. Drugs.com: Premphase Prempro: Package Insert / Prescribing Information.
5. Pfizer Medical Information: PREMPRO® AND PREMPHASE® (conjugated estrogens and medroxyprogesterone acetate tablets).