ALLOPURINOL; LESINURAD - Generic Drug Details

What are the generic sources for allopurinol; lesinurad and what is the scope of freedom to operate?

Allopurinol; lesinurad is the generic ingredient in one branded drug marketed by Ironwood Pharms Inc and is included in one NDA. There are nine patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Allopurinol; lesinurad has two hundred patent family members in forty-two countries.

Summary for ALLOPURINOL; LESINURAD

International Patents:	200
US Patents:	9
Tradenames:	1
Applicants:	1
NDAs:	1
Clinical Trials:	7
DailyMed Link:	ALLOPURINOL; LESINURAD at DailyMed

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for ALLOPURINOL; LESINURAD

Constraining patent/regulatory exclusivity:

8,546,436

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 ALLOPURINOL; LESINURAD

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

Sponsor	Phase
Ardea Biosciences, Inc.	Phase 1
Ardea Biosciences, Inc.	Phase 3

See all ALLOPURINOL; LESINURAD clinical trials

Anatomical Therapeutic Chemical (ATC) Classes for ALLOPURINOL; LESINURAD

M04AA	Preparations inhibiting uric acid production
M04A	ANTIGOUT PREPARATIONS
M04	ANTIGOUT PREPARATIONS
M	Musculo-skeletal system

M04AB	Preparations increasing uric acid excretion
M04A	ANTIGOUT PREPARATIONS
M04	ANTIGOUT PREPARATIONS
M	Musculo-skeletal system

US Patents and Regulatory Information for ALLOPURINOL; LESINURAD

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Ironwood Pharms Inc	DUZALLO	allopurinol; lesinurad	TABLET;ORAL	209203-002	Aug 18, 2017		DISCN	Yes	No	9,216,179
Ironwood Pharms Inc	DUZALLO	allopurinol; lesinurad	TABLET;ORAL	209203-002	Aug 18, 2017		DISCN	Yes	No	8,283,369
Ironwood Pharms Inc	DUZALLO	allopurinol; lesinurad	TABLET;ORAL	209203-001	Aug 18, 2017		DISCN	Yes	No	8,283,369

EU/EMA Drug Approvals for ALLOPURINOL; LESINURAD

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Grunenthal GmbH	Duzallo	allopurinol, lesinurad	EMEA/H/C/004412 Duzallo is indicated in adults for the treatment of hyperuricaemia in gout patients who have not achieved target serum uric acid levels with an adequate dose of allopurinol alone.	Withdrawn	no	no	no	2018-08-23

International Patents for ALLOPURINOL; LESINURAD

Country	Patent Number	Title	Estimated Expiration
Japan	2015172053	２−（５−ブロモ−４−（４−シクロプロピルナフタレン−１−イル）−４Ｈ−１，２，４−トリアゾル−３−イルチオ）酢酸の多形形態およびその使用 (POLYMORPHIC FORMS OF 2-(5-BROMO-4-(4-CYCLOPROPYLNAPHTHALEN-1-YL)-4H-1,2,4-TRIAZOL-3-YLTHIO)ACETIC ACID AND USES THEREOF)
Hungary	E038265
South Korea	20090111357	S-TRIAZOLYL ?-MERCAPTOACETANILIDES AS INHIBITORS OF HIV REVERSE TRANSCRIPTASE

Supplementary Protection Certificates for ALLOPURINOL; LESINURAD

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2217577	PA2019003	Lithuania		PRODUCT NAME: ALOPURINOLIS/LESINURADAS ARBA JO FRAMACINIU POZIURIU PRIIMTINA DRUSKA ARBA DRUSKOS; REGISTRATION NO/DATE: EU/1/18/1300 20180823
2217577	CA 2019 00003	Denmark		PRODUCT NAME: DUZALLO - ALLOPURINOL/LESINURAD OR A PHARMACEUTICALLY ACCEPTABLE SALT OR SALTS THEREOF; REG. NO/DATE: EU/1/18/1300 20180827
2135608	CA 2016 00034	Denmark		PRODUCT NAME: LESINURAD ELLER ET FARMACEUTISK ACCEPTABELT SALT DERAF; REG. NO/DATE: EU1/15/1080 20160222

ALLOPURINOL; LESINURAD Market Analysis and Financial Projection Experimental

Market Dynamics and Financial Trajectory for Allopurinol and Lesinurad

Introduction to Gout and Urate-Lowering Therapies

Gout is a chronic inflammatory arthritis characterized by elevated serum uric acid (sUA) levels, leading to painful gout attacks and potential long-term complications such as kidney stones and tophaceous gout. The management of gout often involves urate-lowering therapies (ULTs), with allopurinol and lesinurad being key players in this therapeutic landscape.

Allopurinol: The First-Line Treatment

Mechanism of Action

Allopurinol is a xanthine oxidase inhibitor that reduces uric acid production in the body. It is the most commonly prescribed medication for gout and is recommended as the first-line ULT[3].

Market Size and Growth

The global allopurinol tablets market is expected to grow significantly, driven by the increasing prevalence of gout and kidney diseases. North America dominates this market, and the segment for gout treatment accounts for the largest share. The market is projected to continue growing due to factors such as rising obesity and cancer rates, which contribute to higher uric acid levels[3].

Key Players

Major pharmaceutical companies like Teva Pharmaceutical Industries Ltd., Dr. Reddys Laboratories, Mylan N.V., Apotex Inc., and Sun Pharmaceutical Industries Limited are key players in the allopurinol market. These companies contribute to the widespread availability and competitive pricing of allopurinol tablets[3].

Lesinurad: A Novel Addition to Gout Treatment

Mechanism of Action

Lesinurad is a selective uric acid reabsorption inhibitor (SURI) that inhibits the URAT1 transporter, thereby increasing uric acid excretion and reducing serum uric acid levels. It is often used in combination with allopurinol to achieve better therapeutic outcomes[1][4].

Clinical Efficacy

Clinical trials, such as the CLEAR 2 study, have shown that lesinurad in combination with allopurinol significantly increases the proportion of patients achieving target sUA levels compared to allopurinol alone. Lesinurad at 200 and 400 mg doses demonstrated superior sUA lowering, with the 200 mg dose being generally well tolerated[1].

Market Impact and Financial Trajectory

Budget Impact

The addition of lesinurad to allopurinol results in an incremental cost, but it is relatively manageable. A budget impact model estimated that the incremental per-member per-month cost would be approximately $0.06 over a five-year period. The cumulative 5-year incremental cost was estimated at $3,633,440 for a one-million-member health plan[2].

Launch and Commercialization

Lesinurad, in combination with allopurinol, was launched as DUZALLO, a once-daily fixed-dose combination treatment. This launch was part of Ironwood Pharmaceuticals' strategic efforts to expand their product portfolio. The commercialization of DUZALLO has contributed to the company's revenue growth, although the specific financial impact is part of broader corporate performance metrics[5].

Market Dynamics

Competitive Landscape

The market for gout treatments is competitive, with allopurinol being the long-standing first-line treatment. The introduction of lesinurad has provided an alternative for patients who do not achieve sufficient sUA reduction with allopurinol alone. Other players, such as febuxostat, also compete in this space, but lesinurad's unique mechanism and combination therapy approach set it apart[1][4].

Regulatory Environment

Lesinurad has undergone extensive clinical trials, including Phase III studies like CLEAR 1 and CLEAR 2, and has met primary endpoints in these trials. Regulatory submissions in the US and EU were expected in the second half of 2014, following the completion of these studies[1][4].

Patient Population and Unmet Needs

More than 50% of patients on allopurinol do not achieve sustained reductions in sUA, highlighting an unmet need for additional therapies. Lesinurad addresses this gap by providing a dual mechanism of action when combined with allopurinol, thereby increasing the proportion of patients achieving target sUA levels[1].

Financial Considerations

Cost-Benefit Analysis

While lesinurad adds to the overall cost of treatment, its efficacy in achieving sUA targets and reducing gout attacks can lead to long-term cost savings by reducing the need for acute gout treatments and managing complications associated with high uric acid levels[2].

Revenue Growth

The launch of DUZALLO and the growing adoption of lesinurad in combination with allopurinol have contributed to revenue growth for companies like Ironwood Pharmaceuticals. The financial performance of these companies reflects the increasing demand for effective gout treatments[5].

Key Takeaways

• Allopurinol remains the first-line treatment for gout, with a well-established market presence and ongoing growth driven by increasing prevalence of gout and related conditions.
• Lesinurad offers a novel approach to gout treatment by inhibiting uric acid reabsorption and is effective in combination with allopurinol, addressing the unmet needs of patients not achieving sufficient sUA reduction with allopurinol alone.
• The budget impact of adding lesinurad is manageable, with an estimated incremental per-member per-month cost of $0.06 over five years.
• The commercialization of DUZALLO has contributed to revenue growth for companies like Ironwood Pharmaceuticals.
• The competitive landscape is dynamic, with lesinurad providing a unique combination therapy approach that sets it apart from other ULTs.

FAQs

Q: What is the primary mechanism of action of allopurinol in treating gout?

A: Allopurinol is a xanthine oxidase inhibitor that reduces uric acid production in the body.

Q: How does lesinurad differ from allopurinol in treating gout?

A: Lesinurad is a selective uric acid reabsorption inhibitor (SURI) that increases uric acid excretion, whereas allopurinol reduces uric acid production.

Q: What are the key findings from the CLEAR 2 study on lesinurad and allopurinol?

A: The CLEAR 2 study showed that lesinurad in combination with allopurinol significantly increased the proportion of patients achieving target sUA levels compared to allopurinol alone.

Q: What is the estimated budget impact of adding lesinurad to allopurinol therapy?

A: The estimated incremental per-member per-month cost is approximately $0.06 over a five-year period.

Q: Which companies are involved in the commercialization of lesinurad?

A: Ironwood Pharmaceuticals, in collaboration with other companies, has commercialized lesinurad as part of the fixed-dose combination treatment DUZALLO.

Sources

1. Lesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy: https://ard.bmj.com/content/76/5/811
2. Budget impact of adding lesinurad for second-line treatment of gout: https://pubmed.ncbi.nlm.nih.gov/29792516/
3. Allopurinol Tablets Market | Market Size, Share & Forecast Analysis: https://www.stratviewresearch.com/1594/allopurinol-tablets-market.html
4. AstraZeneca announces top-line results from phase III monotherapy study of lesinurad in gout patients: https://www.astrazeneca.com/media-centre/press-releases/2013/astrazeneca-lesinurad-study-results-gout-patients-13122013.html
5. Ironwood Pharmaceuticals Provides Third-Quarter 2017 Investor Update: https://investor.ironwoodpharma.com/press-releases/press-release-details/2017/Ironwood-Pharmaceuticals-Provides-Third-Quarter-2017-Investor-Update/default.aspx