Phase III REGION-I Study Shows PEP005 (ingenol mebutate) Gel 0.05% May Reduce Pre-Cancerous Skin Lesions in Patients with Actinic Keratosis

PARSIPPANY, N.J., March 5 /PRNewswire/ -- Specialty pharmaceutical company LEO Pharma today announced that findings from a Phase III study evaluating PEP005 (ingenol mebutate) Gel 0.05% to treat actinic keratosis (AK), a common pre-cursor to skin cancer, were presented at the 68th Annual Meeting of the American Academy of Dermatology (AAD) (Scientific Session Poster Discussion: P105).  Results from REGION-I demonstrated treatment with PEP005 Gel once daily for 2 consecutive days (n=117) on non-head locations resulted in significant clearance of AK lesions when compared with the vehicle or placebo (n=118).  The study showed a 66.7% median reduction in the number of AK lesions, (p<0.0001), a complete clearance rate of 27.4% (p<0.0001) including on the extremely difficult-to-treat back of hand and arm locations, and a partial clearance rate of 44.4% (p<0.0001)(i).

"Cryotherapy has been the gold standard for actinic keratosis for some time, with topical agents also used over a period of weeks to months.  Findings from the REGION-I study suggest that PEP005, a topical Gel administered over just two days, may provide a safe and effective alternative to current therapies," said Neil Swanson, M.D., Department Chairman and Professor of Dermatology, Surgery and Otolaryngology at Oregon Health & Sciences University, and REGION-I principal investigator.

Patients in REGION-I were randomized to receive either PEP005 Gel applied topically as monotherapy to body AK lesions once daily for 2 consecutive days or vehicle. Patients were evaluated on days 3, 8, 15, 29 and 57. The primary objective was to compare the efficacy, as measured by complete clearance, of PEP005 Gel with the vehicle. The secondary objective was the partial clearance of AK lesions. Safety was also assessed by the incidence rate of adverse events (AEs) serious adverse events (SAEs) and AEs leading to discontinuation, as well as by the incidence rate and grade of Local Skin Responses (LSRs), pigmentation and scarring.(i)

The REGION-I study showed PEP005 Gel significantly cleared AK lesions across all anatomical non-head sites at day 57, with complete clearance observed in 32 (27.4%) patients treated with the 0.05% dose vs. 6 (5.1%) in the vehicle group (p=0.0001). For individual anatomical locations, complete clearance rates for active treatment were 0% (0/2) for the back, 16.0% (4/25) for the back of the hand, 16.7% (1/6) for legs, 25.3% (19/75) for the arms and 88.9% (8/9) for the chest. The study also noted partial clearance in 52 (44.4%) of patients in the treatment group and 9 (7.6%) in the vehicle group (p<0.0001). AEs were generally mild to moderate and resolved by day 57. There were no serious AEs, and 98% of patients applied both doses. The most common LSRs were erythema and flaking/scaling. A total of 7 patients in the treatment group experienced pigmentation changes (4 reported improvement and 3 reported worsening of pigmentation) and no patient experienced worsening of scarring. The most common side effects were application site irritation and pruritis.(i)

PEP005 (ingenol mebutate) Gel at AAD

Phase II data evaluating the safety and efficacy of PEP005 in both head and non-head locations were included in AAD poster sessions:

• Multicenter, randomized, double-blind, vehicle-controlled, dose-ranging study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) Gel, 0.005%, 0.01%, and 0.015% when used to treat actinic keratoses (AK) on the head.(ii)

P2913: Electronic Poster

• Multicenter, open-label, dose-area escalation, cohort study to evaluate the safety and tolerability of PEP005 (ingenol mebutate) Gel, 0.05% applied for 2 consecutive days to treatment area(s) of up to a total of 100 cm2 in patients with actinic keratoses (AK) on the extensor (dorsal aspect) forearm(s).(iii)

P2915: Electronic Poster

About REGION-I

REGION-I is a Phase III, multicenter, randomized, parallel-group, double-blind, vehicle-controlled study, evaluating the efficacy and safety of PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days (n=117) compared with vehicle (n=118) to treat patients with actinic keratoses on non-head locations. Eligible patients were randomized 1:1 to PEP005 Gel or vehicle, and were assessed for clearance on days 3, 8, 15, 29 and 57. The primary objective was to compare the efficacy, as measured by complete clearance, of PEP005 Gel with the vehicle. The secondary objective was the partial clearance of AK lesions. Safety was also assessed by the incidence rate of adverse events (AEs) serious AEs and AEs leading to discontinuation, as well as by the incidence rate and grade of Local Skin Responses (LSRs), pigmentation and scarring.(i)

About Actinic Keratosis

Actinic keratosis (AK), also known as solar keratosis or sun spots, is a common pre-cancerous skin condition caused by sun exposure which can develop into skin cancers if left untreated. The number of AK patients is both large and rapidly growing, and AK is a serious health problem. People with fair skin are more likely to develop AK and today it is estimated that 100 million people in the United States, European Union, Canada and Australia have the disease. Less than 10 million people are in treatment.  The American Academy of Dermatology reports that 40 percent of all squamous cell carcinomas begin as AK.

About LEO Pharma

Founded more than 100 years ago, LEO Pharma is an independent, research-based specialty pharmaceutical company committed to the discovery and development of novel drugs for patients within the areas of Dermatology and Critical Care Medicine. With a strong portfolio of approved products – including market leading topical psoriasis treatments TACLONEX®, TACLONEX® Scalp Topical Suspension, DOVONEX® Cream and DOVONEX® Scalp Solution –and a robust pipeline of treatments in development for conditions including psoriasis, eczema and actinic (solar) keratosis, LEO Pharma is one of the leading dermatology companies in the U.S. and the world.

For more information about LEO Pharma, visit www.leopharma.com.

(i) Swanson N. Multicenter, randomized, parallel-group, double-blind, vehicle-controlled study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) Gel, 0/05% in patients with actinic keratosis (AK) on non-head locations. 68th Annual Meeting of the American Academy of Dermatology. Poster session PD01 on Saturday, March 6, 2010 at 7:50 AM EST. Abstract P105.

(ii) Multicenter, randomized, double-blind, vehicle-controlled, dose-ranging study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) Gel, 0.005%, 0.01%, and 0.015% when used to treat actinic keratoses (AK) on the head. Abstract 2913.

(iii) Multicenter, open-label, dose-area escalation, cohort study to evaluate the safety and tolerability of PEP005 (ingenol mebutate) Gel, 0.05% applied for 2 consecutive days to treatment area(s) of up to a total of 100 cm2 in patients with actinic keratoses (AK) on the extensor (dorsal aspect) forearm(s). Abstract 2915.

SOURCE LEO Pharma