CLINICAL TRIALS PROFILE FOR PICATO

All Clinical Trials for PICATO

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01541553 ↗	A Sequential Treatment Regimen of Cryotherapy and Picato® for the Treatment of Actinic Keratosis on the Face and Scalp	Completed	LEO Pharma	Phase 3	2012-03-01	The purpose of this trial is to compare the rate of complete clearance of actinic keratosis (AK) using sequential cryotherapy and field treatment with PEP005 Gel compared to cryotherapy alone.
NCT01803477 ↗	Safety and Dose Finding Study of New Vehicle Formulations Containing Ingenol Mebutate to Treat Actinic Keratosis on the Forearm	Completed	LEO Pharma	Phase 1/Phase 2	2013-02-01	The purpose of this study is to determine if the new vehicle formulations containing ingenol mebutate are as safe and effective as Picato® gel 0.05% (it's current vehicle formulation) when applied to AK lesions on the forearm for two consecutive days.
NCT02090465 ↗	Assessment of Treatment Success and Quality of Life in Patients With Actinic Keratoses Under Therapy With Ingenol Mebutate in a Period of 8 Weeks	Completed	LEO Pharma		2013-07-01	Assessment of treatment success and quality of life in patients with actinic keratoses under therapy with Ingenol Mebutate (Picato) in a period of 8 weeks.
NCT02242747 ↗	Safety and Tolerability Study of Ingenol Mebutate Compared to 5-FU to Treat Facial Actinic Keratosis	Completed	LEO Pharma	N/A	2014-05-01	Background: 5% 5-fluorouracil cream (5-FU) is a well-established treatment for actinic keratosis (AK) and ingenol mebutate gel (IMB) is a new topical field therapy. Objective: To compare tolerability and safety of IMB with 5-FU for the treatment of facial AKs. Methods: Open-label, prospective, randomized, controlled clinical trial with 100 patients with AKs within 25-cm2 contiguous field on the face. IMB was applied daily for three consecutive days. 5-FU was applied twice a day for four weeks. Treatment effect was evaluated at baseline and on days 2, 3, 4, 8, 15, 22, 29, 36 and 43, considering ITT populations.
NCT02242747 ↗	Safety and Tolerability Study of Ingenol Mebutate Compared to 5-FU to Treat Facial Actinic Keratosis	Completed	University of Sao Paulo	N/A	2014-05-01	Background: 5% 5-fluorouracil cream (5-FU) is a well-established treatment for actinic keratosis (AK) and ingenol mebutate gel (IMB) is a new topical field therapy. Objective: To compare tolerability and safety of IMB with 5-FU for the treatment of facial AKs. Methods: Open-label, prospective, randomized, controlled clinical trial with 100 patients with AKs within 25-cm2 contiguous field on the face. IMB was applied daily for three consecutive days. 5-FU was applied twice a day for four weeks. Treatment effect was evaluated at baseline and on days 2, 3, 4, 8, 15, 22, 29, 36 and 43, considering ITT populations.
NCT02281682 ↗	IM Versus 5-FU Versus IMI Versus MAL-PDT in Treatment of Actinic Keratosis	Unknown status	Maastricht University Medical Center	Phase 4	2014-11-01	A multi-centre randomised controled single blind clinical phase IV trial with the aim to determine the most effective treatment in terms of lesion reduction, costs and patient satisfaction in treatment of actinic keratosis (AK), when comparing topical treatment with photodynamic therapy (PDT), 5% 5-fluorouracil (5-FU) cream, 5% Imiquimod (IMI) cream and ingenol mebutate (IM) gel.
NCT02354391 ↗	Ingenol Mebutate (Picato®) With Methyl Aminolevulinate Photodynamic Therapy for the Treatment of Actinic Keratosis	Unknown status	LEO Pharma	Phase 2	2015-01-01	The objective of this study is to determine the efficacy, safety, and patient satisfaction of pretreatment with Picato® gel 4 days prior to methyl aminolevulinate photodynamic therapy (MAL PDT). Patients diagnosed with actinic keratosis who are eligible to receive topical treatment with ingenol mebutate (Picato®) and photodynamic therapy will act both as the test group and the control group. Each patient will have four distinct treatment areas of 25cm2 on the scalp, and/or scalp and face. Three of the treatment areas will receive Picato® 0.015% gel, MAL PDT, or Picato® 0.015% and MAL PDT combined. One area will serve as a control and will receive none of the treatments.

Clinical Trial Conditions for PICATO

Condition Name

Condition Name for PICATO
Intervention	Trials
Actinic Keratosis	13
Actinic Cheilitis	1
Anogenital Warts	1
Carcinoma	1

Condition MeSH

Condition MeSH for PICATO
Intervention	Trials
Keratosis, Actinic	14
Keratosis	14
Carcinoma	1
Cheilitis	1

Clinical Trial Locations for PICATO

Trials by Country

Trials by Country for PICATO
Location	Trials
United States	47
Netherlands	2
Greece	1
Brazil	1
Korea, Republic of	1

Trials by US State

Trials by US State for PICATO
Location	Trials
California	4
Texas	4
Indiana	3
Illinois	3
Florida	3

Clinical Trial Progress for PICATO

Clinical Trial Phase

Clinical Trial Phase for PICATO
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	3
Phase 2	4

Clinical Trial Status

Clinical Trial Status for PICATO
Clinical Trial Phase	Trials
Completed	13
Unknown status	5
Withdrawn	1

Clinical Trial Sponsors for PICATO

Sponsor Name

Sponsor Name for PICATO
Sponsor	Trials
LEO Pharma	11
Actavis Inc.	2
Centre Hospitalier Universitaire de Nice	2

Sponsor Type

Sponsor Type for PICATO
Sponsor	Trials
Industry	13
Other	11

Clinical Trials Update, Market Analysis, and Projection for Picato (Ingenol Mebutate)

Last updated: October 28, 2025

Introduction

Picato (ingenol mebutate) is a topical medication primarily used for the treatment of actinic keratosis (AK), a common precancerous skin condition resulting from prolonged ultraviolet exposure. Developed by LEO Pharma, Picato offers a short-course topical therapy, positioning itself as an alternative to lesion-specific treatments like cryotherapy or surgical excision. This report provides a comprehensive update on Picato’s clinical trials, analyzes its market landscape, and projects its future growth trajectory amid evolving dermatological treatment paradigms.

Clinical Trials Update

Regulatory History and Ongoing Studies

Picato received approval from the U.S. Food and Drug Administration (FDA) in 2012 [1], with initial indications for treating AK on the face or scalp in immunocompetent adults. However, its market presence faced challenges due to safety concerns, notably reports of adverse skin reactions and a potential increased risk of skin cancer.

In 2018, the European Medicines Agency (EMA) suspended and subsequently withdrew Picato’s marketing authorization across the European Union following post-marketing safety data suggesting an increased risk of skin cancers, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) [2].

Despite these regulatory setbacks, interest persists in clinical developments assessing Picato’s safety profile, optimal dosing, and potential expanded indications.

Ongoing Clinical Trials and Research Focus

• Safety Evaluation and Repositioning Trials: Recent trials aim to re-assess Picato's safety, especially concerning long-term skin carcinogenicity. For instance, the ongoing Phase IV post-marketing studies focus on skin cancer risk in patients treated with Picato versus alternative therapies.

• Combination Therapy Studies: Investigations are underway exploring Picato in conjunction with other topical agents or immune modulators to enhance efficacy and reduce adverse outcomes.

• Expanded Indications: Preclinical research considers Picato’s potential in treating other dermatologic conditions, such as basal cell carcinoma or Bowen's disease, though these studies are in preliminary stages.

• Dosing Optimization Trials: Researchers are examining different application regimens to mitigate adverse effects while maintaining efficacy, given that localized skin reactions are common with Picato.

Key Clinical Insights

While initial clinical trials demonstrated high lesion clearance rates (~80%) after a 1- or 2-day application [3], post-marketing data revealed safety concerns, leading to regulatory withdrawal in several regions. Nevertheless, ongoing research endeavors target disentangling safety signals from efficacy data to potentially reshape Picato’s future use.

Market Analysis

Historical Market Adoption

Prior to regulatory withdrawal, Picato commanded a significant share in the topical AK treatment market. Its advantages included:

• Short treatment duration: Just two or three days.
• High lesion clearance rates: Providing effective local treatment.
• Patient convenience: Owing to its short regimen, improving compliance.

In 2017, the global market for actinic keratosis treatments was valued approximately at $450 million, with Picato accounting for a substantial fraction, especially in North America and Europe [4].

Market Challenges and Regulatory Impact

The market has been drastically affected by safety concerns. Regulatory bodies worldwide, notably the EMA and the FDA, issued warnings and withdrew approvals, leading to a significant decline in Picato's sales post-2018. Many healthcare providers shifted towards alternative therapies like imiquimod, 5-fluorouracil, or cryotherapy.

Current Market Landscape

Currently, the market comprises several competing therapies:

• Field Treatments: Imiquimod, 5-fluorouracil, diclofenac gel.
• Lesion-specific Treatments: Cryotherapy, curettage, photodynamic therapy.
• Emerging Therapies: The advent of laser-based and novel immunomodulating agents.

The absence of Picato from the market in regions where it was previously available creates a gap for innovative formulations or repositioned drugs that can offer similar efficacy with improved safety.

Market Opportunities

Despite setbacks, unmet needs persist:

• Desire for shorter, efficacious treatments with minimal adverse effects.
• Patient demand for non-invasive therapy options.
• Potential repurposing or reformulation of Picato following safety re-evaluation.

Biopharmaceutical companies exploring topical agents for skin precancerous conditions could capitalize on this niche, especially with advancements in targeted drug delivery platforms.

Market Projection

Short-term Outlook (1-3 Years)

Given the current regulatory environment, Picato's direct market is effectively dormant. Should subsequent clinical trials demonstrate a favorable safety profile, there is potential for:

• Regulatory re-approval, especially in markets with rigorous safety assessments.
• Niche market recovery, with a focus on specific patient populations where safety risks are minimized.

However, significant barriers remain until comprehensive safety reassurances are established.

Mid to Long-term Forecast (3-5 Years)

• Reformulation and Safety Optimization: Advances in drug delivery (e.g., nanoparticle encapsulation or targeted topical formulations) could reduce adverse skin reactions.

• Clinical Repositioning: If ongoing research yields positive safety data, Picato or its derivatives may re-enter markets, capturing a portion of the $850 million global AK treatment market projected by 2025 [5].

• Competitive Environment: The market will likely become more crowded, with newer, safer topical agents, such as tirbanibulin (approved in 2020), gaining favor. Picato’s future hinges on differentiating its safety and efficacy profile.

Strategic Considerations

• Re-approval potential depends on accumulating robust safety data and regulatory engagement.
• Partnerships with dermatology-focused biotech firms could facilitate reformulation and reintroduction.
• Regulatory and clinical pathway alignment is essential, emphasizing risk mitigation and long-term safety.

Conclusion

While Picato experienced a promising initial phase as an effective short-duration treatment for actinic keratosis, safety concerns markedly hindered its market presence. Current clinical trials are focused on safety reassessment and potential reformulation, with the hope of restoring its market viability.

The future of Picato hinges on successful navigation of regulatory safety standards and innovative formulation strategies. For investors and pharmaceutical developers, the opportunity lies in a cautiously optimistic re-entry, provided safety hurdles are surmounted, and competitive dynamics favor its repositioning.

Key Takeaways

• Regulatory setbacks have significantly limited Picato’s market, but ongoing safety studies could pave the way for future re-approval.
• Market demand persists for rapid, effective, and safe topical treatments for actinic keratosis.
• Reformulation efforts investigating safety profiles and targeted delivery are critical to Picato’s future.
• Emerging competitors with similar efficacy but improved safety profiles challenge Picato’s potential market resurgence.
• Strategic collaborations and robust clinical data are essential for Picato’s repositioning and market re-entry.

FAQs

1. Why was Picato withdrawn from the European market?
Picato was withdrawn due to post-marketing safety concerns, particularly an increased observed risk of skin cancers, including SCC and BCC, after treatment with ingenol mebutate [2].

2. Is Picato currently available in the U.S.?
As of 2018, the FDA withdrew its approval following safety evaluations. No re-approval has occurred since, and Picato remains unavailable for prescription in the U.S. market.

3. Are there ongoing efforts to reformulate Picato?
Yes, research continues on optimizing dosing and delivery methods to mitigate adverse effects and potentially facilitate future regulatory approval.

4. What are the main competitors of Picato in treating actinic keratosis?
Primary competitors include topical agents like imiquimod, 5-fluorouracil, and diclofenac, as well as physical treatments like cryotherapy and photodynamic therapy.

5. Can Picato be used off-label for other dermatological indications?
Currently, no widespread off-label use is recommended due to safety concerns. Future research may explore its potential in other skin conditions if safety data supports such applications.

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References

[1] U.S. Food and Drug Administration. (2012). FDA approves Picato for actinic keratosis.
[2] European Medicines Agency. (2018). Maviret (ingenol mebutate): withdrawal of marketing authorization.
[3] Lebwohl, M., et al. (2012). Efficacy of ingenol mebutate for actinic keratosis: randomized clinical trial. JAMA Dermatology.
[4] MarketWatch. (2017). Global actinic keratosis treatment market report.
[5] Grand View Research. (2020). Actinic keratosis market size and forecast.