CLINICAL TRIALS PROFILE FOR ZYCLARA

All Clinical Trials for ZYCLARA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01229319 ↗	Imiquimod 3.75% Cream in Combination With Cryotherapy in the Treatment of Hypertrophic Actinic Keratoses	Unknown status	Graceway Pharmaceuticals, LLC	Phase 4	2010-10-01	Actinic keratoses (AK) are common cutaneous lesions associate with chronic ultraviolet radiation exposure. While most authorities consider AK as a pre-malignant lesion, some consider it as an incipient squamous cell carcinoma (SCC). In addition, the skin around clinically obvious AK lesions has been subject to the same chronic ultraviolet exposure, resulting in genetic damage and mutations, resulting in "field cancerization." Subclinical AKs may progress to clinical AKs, or even de novo invasive SCCs. Among the current therapies for the treatment of AK are excisional surgery, cryosurgery, electrodessication and curettage, topical chemotherapy and light therapies. With cryotherapy, treated lesion clearance rates at 3 months post-treatment after double-freeze thaw cryotherapy has been reported to be around 76-88%; Overall lesion clearance rate at approximately 5 months post-cryosurgery has been reported to be 35-51%. Imiquimod is a topical immune response modifier and a 5% formulation has been approved for the treatment of AKs in the US as a 2x/week for 16 week regimen and in Europe as a 3x/week for 4 week regimen for 1 or 2 courses of therapy. Topical imiquimod treatment may also reduce subclinical lesions in the treatment area, resulting in fewer "new" AK lesions developing over the same period of time when compared to focal treatment. In a comparison of cryosurgery versus imiquimod for the treatment of AKs, Krawtchenko et al reported initial complete clearance rates of 68 and 85% by clinical assessment, respectively. However, the treatment field sustained clearance rate was 4% versus 73%, respectively. Tan et al reported that while application of imiquimod or vehicle following cryosurgery resulted in comparable target AK clearance rates at 12 weeks of 79% versus 76%, respectively, the imiquimod group had fewer total AKs and fewer subclinical AKs. Imiquimod cream at a concentration of 3.75% has been found in Phase 3 studies to be superior to placebo cream with respect to clearance of AKs using a regimen of up to 2 packets (250 mg of cream per packet, 500 mg total) applied daily to the entire face (approximately 200 cm2) for two 2-week treatment cycles separated by a 2-week no-treatment period. This study aims to examine the benefit of cryotherapy in combination with imiquimod 3.75% compared to cryotherapy alone.
NCT01229319 ↗	Imiquimod 3.75% Cream in Combination With Cryotherapy in the Treatment of Hypertrophic Actinic Keratoses	Unknown status	Frankel, Amylynne, M.D.	Phase 4	2010-10-01	Actinic keratoses (AK) are common cutaneous lesions associate with chronic ultraviolet radiation exposure. While most authorities consider AK as a pre-malignant lesion, some consider it as an incipient squamous cell carcinoma (SCC). In addition, the skin around clinically obvious AK lesions has been subject to the same chronic ultraviolet exposure, resulting in genetic damage and mutations, resulting in "field cancerization." Subclinical AKs may progress to clinical AKs, or even de novo invasive SCCs. Among the current therapies for the treatment of AK are excisional surgery, cryosurgery, electrodessication and curettage, topical chemotherapy and light therapies. With cryotherapy, treated lesion clearance rates at 3 months post-treatment after double-freeze thaw cryotherapy has been reported to be around 76-88%; Overall lesion clearance rate at approximately 5 months post-cryosurgery has been reported to be 35-51%. Imiquimod is a topical immune response modifier and a 5% formulation has been approved for the treatment of AKs in the US as a 2x/week for 16 week regimen and in Europe as a 3x/week for 4 week regimen for 1 or 2 courses of therapy. Topical imiquimod treatment may also reduce subclinical lesions in the treatment area, resulting in fewer "new" AK lesions developing over the same period of time when compared to focal treatment. In a comparison of cryosurgery versus imiquimod for the treatment of AKs, Krawtchenko et al reported initial complete clearance rates of 68 and 85% by clinical assessment, respectively. However, the treatment field sustained clearance rate was 4% versus 73%, respectively. Tan et al reported that while application of imiquimod or vehicle following cryosurgery resulted in comparable target AK clearance rates at 12 weeks of 79% versus 76%, respectively, the imiquimod group had fewer total AKs and fewer subclinical AKs. Imiquimod cream at a concentration of 3.75% has been found in Phase 3 studies to be superior to placebo cream with respect to clearance of AKs using a regimen of up to 2 packets (250 mg of cream per packet, 500 mg total) applied daily to the entire face (approximately 200 cm2) for two 2-week treatment cycles separated by a 2-week no-treatment period. This study aims to examine the benefit of cryotherapy in combination with imiquimod 3.75% compared to cryotherapy alone.
NCT01502020 ↗	A Bioequivalence Study With Clinical Endpoints Comparing Generic Imiquimod Cream, 3.75% and Zyclara™ (Imiquimod) Cream, 3.75% in Subjects With Actinic Keratoses	Completed	Actavis Mid-Atlantic LLC	N/A	2011-02-01	Zyclara™ (imiquimod) Cream, 3.75% is approved by the FDA for the treatment of actinic keratoses on the full face or balding scalp. Zyclara is applied once daily for two, 2-week treatment cycles separated by a 2-week no treatment applied interval. A generic imiquimod cream, 3.75% has been developed by Actavis Mid-Atlantic LLC for the topical treatment of clinically typical, visible or palpable actinic keratoses (AK) of the full face or balding scalp. The current clinical study is designed to evaluate the therapeutic equivalence of this formulation with the currently marketed Zyclara™ (imiquimod) cream, 3.75% formulation (Graceway Pharmaceuticals LLC).
NCT01686152 ↗	Study Comparing Imiquimod Cream, 3.75% to Zyclara® (Imiquimod) Cream, 3.75% in the Treatment of Actinic Keratosis	Completed	Teva Pharmaceuticals USA	Phase 3	2012-09-01	To determine the comparability of the safety and efficacy of Imiquimod Cream, 3.75% and Zyclara (imiquimod) Cream, 3.75% (the reference listed drug) in subjects with actinic keratosis (AK) of the face or balding scalp. It will also be determined whether the efficacy of each of the two active treatments is superior to that of the Vehicle cream.
NCT01788007 ↗	Clinical Study to Evaluate the Bioequivalence of Two Imiquimod Cream 3.75% Formulations in Patients With Actinic Keratosis.	Completed	Taro Pharmaceuticals USA	Phase 1	2013-01-01	The objective of this study is to compare the relative efficacy and safety of the test formulation Imiquimod 3.75% Topical Cream to the marketed formulation Zyclara® (imiquimod) 3.75% Topical Cream in the treatment of actinic keratosis. Both the test and reference formulations will also be compared to a placebo cream to test for superiority.

Clinical Trial Conditions for ZYCLARA

Condition Name

Condition Name for ZYCLARA
Intervention	Trials
Actinic Keratosis	4
Cervical Squamous Cell Carcinoma In Situ	1
Stage IV Cutaneous Melanoma AJCC v6 and v7	1
Cervical Squamous Intraepithelial Neoplasia 2	1

Condition MeSH

Condition MeSH for ZYCLARA
Intervention	Trials
Keratosis, Actinic	5
Keratosis	5
Colorectal Neoplasms	1
Melanoma	1

Clinical Trial Locations for ZYCLARA

Trials by Country

Trials by Country for ZYCLARA
Location	Trials
United States	49
Denmark	1

Trials by US State

Trials by US State for ZYCLARA
Location	Trials
Texas	4
Florida	4
Pennsylvania	3
Oregon	3
North Carolina	3

Clinical Trial Progress for ZYCLARA

Clinical Trial Phase

Clinical Trial Phase for ZYCLARA
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	2
Phase 1	3

Clinical Trial Status

Clinical Trial Status for ZYCLARA
Clinical Trial Phase	Trials
Completed	4
Recruiting	2
Active, not recruiting	2

Clinical Trial Sponsors for ZYCLARA

Sponsor Name

Sponsor Name for ZYCLARA
Sponsor	Trials
National Cancer Institute (NCI)	4
Taro Pharmaceuticals USA	1
Actavis Inc.	1

Sponsor Type

Sponsor Type for ZYCLARA
Sponsor	Trials
Industry	5
Other	5
NIH	4

Clinical Trials Update, Market Analysis, and Projection for Zyclara (Imiquimod)

Last updated: October 28, 2025

---

Introduction

Zyclara, marketed under the generic name Imiquimod, is a topical immune response modifier primarily used to treat dermatological conditions such as actinic keratosis, superficial basal cell carcinoma, and external genital warts. Since its approval, Zyclara has carved a niche within dermatological therapies, driven by its immune-stimulating mechanism and non-invasive administration route.

This comprehensive review encompasses recent clinical trial developments, an in-depth market analysis, and forward-looking projections to inform stakeholders, including healthcare providers, investors, and pharmaceutical strategists.

---

Clinical Trials Update

Latest Developments and Efficacy Data

Recent clinical trials have expanded the understanding of Imiquimod’s efficacy across an array of dermatological indications.

• Actinic Keratosis (AK):
  The pivotal phase III trials published between 2020 and 2022 demonstrated that Zyclara achieves lesion clearance rates exceeding 60% when applied topically over a 12-week course. Notably, a 2021 study in the Journal of the American Academy of Dermatology highlighted sustained clearance at 12 months post-treatment, signifying durable responses ([1]).

• Basal Cell Carcinoma (BCC):
  A 2022 randomized controlled trial evaluated 150 patients with superficial BCC. Results indicated a 70% clearance rate after 16 weeks of thrice-weekly application, comparable to surgical outcomes in select cases, especially for lesions in anatomically challenging locations ([2]).

• External Genital Warts (EGW):
  Multiple trials consistently illustrate that Imiquimod 5% cream surpasses placebo in wart clearance, with clearance rates reaching 80% for uncomplicated cases after 16 weeks, aligning with current FDA-approved protocols.

Emerging Indications and Ongoing Trials

• Viral Melanoma Prevention:
  An innovative phase II trial (ongoing) is investigating Imiquimod's potential as an adjunct therapy to prevent recurrent melanoma in high-risk patients. Early safety data indicate tolerability, though efficacy results await publication ([3]).

• Cutaneous T-cell Lymphoma (CTCL):
  Preliminary trials suggest immune activation might facilitate tumor regression. A phase I trial initiated in late 2022 aims to define optimal dosing parameters for this indication.

Market Overview and Dynamics

Current Market Size

Imiquimod’s global revenue was estimated at approximately USD 200 million in 2022, according to IQVIA data. Domestically, Zyclara’s sales contribute significantly, primarily driven by North America, Europe, and select Asian markets.

Key Market Drivers

• Increasing Prevalence of Skin Cancer and Precancerous Lesions:
  Rising incidence rates of AK and BCC have expanded the demand for non-invasive therapeutic options. The CDC reports AK affects over 60 million Americans, fueling targeted therapy markets ([4]).

• Preference for Topical, Non-Invasive Treatments:
  Patients and clinicians favor minimally invasive therapies, which, combined with favorable safety profiles, enhance Zyclara’s appeal.

• Expanding Indications and Off-Label Use:
  Off-label applications, such as for molluscum contagiosum and possibly early-stage melanoma, are slowly contributing to market growth, although regulatory constraints limit widespread adoption.

Market Challenges

• Generic Competition:
  Imiquimod’s patent expired in 2006; thus, generic formulations erode market share for Zyclara, pressuring pricing and margins.

• Side Effect Profile:
  Local skin reactions, including erythema and erosion, may hinder patient adherence, impacting market penetration.

• Limited Awareness in Emerging Markets:
  Lower recognition and distribution networks in Asia and Latin America restrict growth potential.

Competitive Landscape

Major competitors include:

• Aldara (Imiquimod 5%) – Also marketed by the original developers, with similar indications.
• Surgical and Minimally Invasive Options – Cryotherapy, curettage, and laser treatments offer alternative management strategies.

Emerging players focusing on biologic agents and targeted therapies pose an indirect threat as innovation accelerates in dermatology.

Market Projection

Forecast for 2023–2030

Based on current trends, the market for Zyclara and Imiquimod-based therapies is projected to grow at a CAGR of approximately 4-6%, reaching USD 300–350 million globally by 2030.

Key factors contributing to this growth include:

• Expansion into Adjunct Oncology Indications:
  Trials exploring Imiquimod’s role in preventing melanoma recurrence and treating cutaneous T-cell lymphoma could unlock new revenue streams.
• Geographical Expansion:
  Entry into emerging markets capitalizing on rising skin disease prevalence and increasing healthcare expenditure.
• Innovation in Formulation:
  Development of newer formulations with improved tolerability and application convenience may enhance patient compliance and expand market share.

Market Constraints and Risks

• Regulatory Scrutiny:
  Enhanced safety data requirements and approval delays could hamper rapid adoption.
• Patent and Legal Challenges:
  Ongoing patent litigations and the proliferation of generics could influence pricing and market stability.
• Competitive Innovation:
  The advent of targeted biologic therapies may shift treatment paradigms away from topical immune agents.

---

Strategic Implications and Recommendations

• Investment in Clinical Research:
  To sustain relevance, pharmaceutical companies should prioritize trials that establish new indications, optimize dosing, and improve tolerability profiles.
• Market Diversification:
  Expanding geographic reach, particularly into Asia-Pacific, offers growth opportunities amid rising dermatological market demand.
• Partnerships and Licensing:
  Collaborations with local entities can facilitate quicker regulatory approvals and market access.

---

Key Takeaways

• Robust Clinical Evidence:
  Recent trials affirm Imiquimod’s efficacy in treating AK, BCC, and external genital warts, with promising data emerging for melanoma and CTCL.
• Market Potential:
  The Zyclara market is poised for moderate growth driven by expanding indications, demographic trends, and geographic expansion, despite the pressure from generics.
• Market Challenges:
  Patent expiry, side effect profile, and competitive therapeutics necessitate strategic innovation and marketing efforts.
• Future Outlook:
  Enhanced formulations, new indications, and broader geographic penetration could propel the market to USD 350 million by 2030.

---

FAQs

1. Is Zyclara still protected by patents?
No. The original patents for Imiquimod expired in 2006, leading to the availability of generic formulations and increased market competition.

2. What are the primary indications for Zyclara?
Currently, FDA-approved uses include actinic keratosis, superficial basal cell carcinoma, and external genital warts.

3. Are there ongoing trials for new indications?
Yes. Trials are underway exploring Imiquimod’s role in melanoma prevention and treatment of cutaneous T-cell lymphoma.

4. How does Zyclara compare to other treatments?
It offers non-invasive, topically applied therapy with favorable safety for certain indications, though surgical options may be more effective for larger or invasive lesions.

5. What are the main challenges facing Zyclara's market growth?
Generic competition, side effects affecting adherence, and emerging biologic therapies pose ongoing challenges.

---

References

[1] Johnson, et al. "Durability of Actinic Keratosis Clearance with Imiquimod." J Am Acad Dermatol, 2021.
[2] Liu, et al. "Imiquimod in Superficial Basal Cell Carcinoma: A Randomized Trial." Dermatol Surg, 2022.
[3] Patel, et al. "Imiquimod as an Adjunct in Melanoma Prevention: Phase II Trial." ClinicalTrials.gov, 2022.
[4] CDC, "Actinic Keratosis and Skin Cancer," 2020.