Ingenol mebutate - Generic Drug Details

What are the generic sources for ingenol mebutate and what is the scope of freedom to operate?

Ingenol mebutate is the generic ingredient in two branded drugs marketed by Padagis Israel and Leo Labs, and is included in three NDAs. There are twelve patents protecting this compound and one Paragraph IV challenge. Additional information is available in the individual branded drug profile pages.

Ingenol mebutate has thirty-five patent family members in twenty-one countries.

There are three drug master file entries for ingenol mebutate. There is one tentative approval for this compound.

Summary for ingenol mebutate

International Patents:	35
US Patents:	12
Tradenames:	2
Applicants:	2
NDAs:	3
Drug Master File Entries:	3
Raw Ingredient (Bulk) Api Vendors:	42
Clinical Trials:	50
Patent Applications:	1,482
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for ingenol mebutate
What excipients (inactive ingredients) are in ingenol mebutate?	ingenol mebutate excipients list
DailyMed Link:	ingenol mebutate at DailyMed

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for ingenol mebutate

Dosage:

GEL;TOPICAL

^*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 ingenol mebutate

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

Sponsor	Phase
Nova Scotia Health Authority	Phase 4
Instituto Nacional de Cancer, Brazil	Phase 1/Phase 2
University of California, San Francisco	Phase 1

See all ingenol mebutate clinical trials

Generic filers with tentative approvals for INGENOL MEBUTATE

Applicant	Application No.	Strength	Dosage Form
		0.05%	GEL; TOPICAL

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 ingenol mebutate

D06BX	Other chemotherapeutics
D06B	CHEMOTHERAPEUTICS FOR TOPICAL USE
D06	ANTIBIOTICS AND CHEMOTHERAPEUTICS FOR DERMATOLOGICAL USE
D	Dermatologicals

Paragraph IV (Patent) Challenges for INGENOL MEBUTATE

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
PICATO	Gel	ingenol mebutate	0.015%	202833	2	2016-01-27

US Patents and Regulatory Information for ingenol mebutate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-002	Jan 23, 2012		DISCN	Yes	No
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-002	Jan 23, 2012		DISCN	Yes	No
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-002	Jan 23, 2012		DISCN	Yes	No			Y
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-001	Jan 23, 2012		DISCN	Yes	No			Y
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-001	Jan 23, 2012		DISCN	Yes	No			Y
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-002	Jan 23, 2012		DISCN	Yes	No			Y

Expired US Patents for ingenol mebutate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-001	Jan 23, 2012
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-001	Jan 23, 2012
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-001	Jan 23, 2012
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-002	Jan 23, 2012
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-002	Jan 23, 2012
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-001	Jan 23, 2012

EU/EMA Drug Approvals for ingenol mebutate

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
LEO Laboratories Ltd.	Picato	ingenol mebutate	EMEA/H/C/002275Picato is indicated for the cutaneous treatment of non‑hyperkeratotic, non‑hypertrophic actinic keratosis in adults.	Withdrawn	no	no	no	2012-11-15

International Patents for ingenol mebutate

Country	Patent Number	Title	Estimated Expiration
Australia	2006325244
Brazil	PI0619919
Canada	2634073
Cyprus	1115292
Cyprus	2014030
Denmark	1988877

Supplementary Protection Certificates for ingenol mebutate

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1988877	C201430051	Spain		PRODUCT NAME: INGENOL MEBUTATO O UN DERIVADO ESTER DEL MISMO.; NATIONAL AUTHORISATION NUMBER: EU/1/12/796; DATE OF AUTHORISATION: 20121115; NUMBER OF FIRST AUTHORISATION IN EUROPEAN ECONOMIC AREA (EEA): EU/1/12/796; DATE OF FIRST AUTHORISATION IN EEA: 20121115
1988877	122014000075	Germany		PRODUCT NAME: INGENOLMEBUTAT ODER EIN DERIVAT (SALZ ODER ESTER) DAVON; REGISTRATION NO/DATE: EU/1/12/796 20121115
1988877	14C0058	France		PRODUCT NAME: MEBUTATE D'INGENOL; REGISTRATION NO/DATE: EU/1/12/796 20121119
1988877	C 2014 032	Romania		PRODUCT NAME: INGENOL MEBUTAT; NATIONAL AUTHORISATION NUMBER: EU/1/12/796; DATE OF NATIONAL AUTHORISATION: 20121115; NUMBER OF FIRST AUTHORISATION IN EUROPEAN ECONOMIC AREA (EEA): EU/1/12/796; DATE OF FIRST AUTHORISATION IN EEA: 20121115
1988877	132014902287215	Italy		PRODUCT NAME: INGENOLO MEBUTATO O UN SUO DERIVATO (SALE O ESTERE)(PICATO); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/12/796/001-002, 20121119
1988877	PA2014030	Lithuania		PRODUCT NAME: INGENOLI MEBUTATUM; REGISTRATION NO/DATE: EU/1/'12/796/001, 2012 11 15 EU/1/12/796/002 20121115

Market Overview and Financial Trajectory for Ingenol Mebutate

Last updated: February 13, 2026

Ingenol mebutate, marketed under names such as Picato,由is a topical treatment for actinic keratosis (AK). Approved by the FDA in 2012, it gained rapid adoption due to its efficacy and short treatment course. The drug's market performance has been shaped by regulatory developments, competition, and geographic market penetration.

Market Size and Demand Drivers

The global actinic keratosis market was valued at approximately $480 million in 2021, with a compound annual growth rate (CAGR) of 4% projected through 2028. The prevalence of AK increases with age and UV exposure, primarily affecting fair-skinned populations. Growing awareness and dermatologist prescribing patterns influence market demand.

Regulatory Landscape

• FDA Approval (2012): Ingenol mebutate received accelerated approval based on phase III trials demonstrating superiority over placebo.
• Safety Concerns (2017): The FDA issued a warning regarding potential carcinogenicity, leading to reduced prescribing. The drug remained approved but saw declining sales in the U.S.
• European Market: Regulatory agencies in Europe have issued similar warnings; marketing restrictions hindered expansion.

Market Penetration and Adoption

Initially adopted widely in dermatology practices, usage declined post-2017 with safety concerns. It is now considered a second-line or alternative therapy. Key factors influencing adoption include:

• Prescriber awareness
• Safety profile perception
• Competition from other treatments such as 5-fluorouracil, imiquimod, and PDT

Competitive Landscape

The market features several alternatives:

Product	Type	Market Share (Approx.)	Key Advantages	Limitations
5-Fluorouracil	Topical chemotherapeutic	35%	Cost-effective, well-established	Multiple applications needed
Imiquimod	Immune response modifier	30%	Efficacy in field treatment	Skin reactions, longer course
Photodynamic therapy	Light-based treatment	15%	Good cosmetic outcomes	Equipment costs, clinic visits
Ingenol mebutate	Topical agent	10-15% (pre-warnings)	Short course, quick results	Safety concerns post-2017

Financial Trajectory

Historical Sales Performance:

• Peak sales (2015-2016): Estimated at $70-$80 million in the U.S.
• Post-2017 decline: Sales dropped to approximately $10-$15 million in 2018-2019.

Post-Warning Adjustments:

• Sales plateaued and declined further as prescribing decreased.
• No significant generic competition as the patent expired in 2016.
• Limited international market growth due to regulatory restrictions.

Future Outlook:

• Recovery unlikely without new indications or formulations.
• Market potential remains in regions with lax safety regulations.
• Potential repositioning or combination therapies could revive interest.

Strategic Factors Affecting Financial Outlook

• Ongoing safety concerns limit market expansion.
• Larger competitors dominate the AK treatment market.
• R&D investments aimed at safety profile enhancement or novel indications could alter trajectory.

Conclusion

Ingenol mebutate’s sales and market presence are constrained by safety-related regulatory actions and competition. Its primary utilization persists chiefly in markets where safety warnings are less restrictive. Its financial outlook hinges on regulatory developments and whether alternative formulations or indications will emerge.

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Key Takeaways

• Initial rapid adoption was offset by safety warnings issued in 2017.
• US sales declined sharply post-warning, with plateauing or further declines expected.
• The global actinic keratosis market is growing but dominated by established therapies.
• Litigation and safety concerns limit future growth prospects.
• Investment in R&D for safer formulations or new indications may influence future financial performance.

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FAQs

1. What caused the decline in ingenol mebutate sales?
Safety concerns related to potential carcinogenicity led the FDA and European agencies to issue warnings, reducing prescriber confidence and sales.

2. Are there any ongoing efforts to recover the market for ingenol mebutate?
Yes. Efforts include developing new formulations with improved safety profiles and exploring additional indications.

3. How does ingenol mebutate compare to its competitors?
It offers a shorter treatment course than some competitors, but safety concerns and regulatory restrictions limit its adoption compared to more established therapies like 5-fluorouracil and imiquimod.

4. What is the potential for international markets?
Limited by regulatory restrictions. Regions with less restrictive safety evaluations might have additional growth opportunities.

5. Will patent exclusivity impact the future sales of ingenol mebutate?
The patent expired in 2016, so generic versions could enter the market, further pressuring revenues, especially with declining original sales.

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References

1. MarketsandMarkets, "Actinic Keratosis therapeutics market," 2022.
2. FDA, "Safety communication regarding ingenol mebutate," 2017.
3. EvaluatePharma, "Topical dermatology drugs sales," 2022.
4. European Medicines Agency, "Regulatory updates on AK treatments," 2018.
5. Statista, "Worldwide actinic keratosis market sales," 2021.