Positive Preliminary Results of Phase IIb AK Study
• Statistically significant lesion clearance at all
• Suggest favourable safety profile at all doses
• Suggest clear dose response to drug
• High patient satisfaction with treatment and outcomes
BRISBANE, Australia 19 July 2007 Peplin Limited (ASX:PEP) today announced positive preliminary results of PEP005-006 its 220 patient US-based phase IIb actinic (solar) keratosis (AK) clinical study. AKs are common precancerous skin lesions, caused by sun exposure, a portion of which develop into skin cancer.
The PEP005-006 dose finding clinical study was designed to evaluate the safety, tolerability and efficacy of three different dosages of PEP005 Topical for AK when used as a field-directed therapy for the treatment of AK on the trunk, extremities and scalp.
At all doses the drug suggested a favourable safety profile and was well tolerated; side effects comprised primarily transient local skin responses at the treatment site and generally resolved in two to four weeks. There were no drug related serious adverse events reported. In addition, a 2 or 3 day course of PEP005 Topical for AK delivered statistically significant lesion clearance by all measures and at all doses studied. These results suggest a clear relationship between activity of the drug and dosage in all treatment groups (dose response). On the primary efficacy measure, in the highest dose group, 75% of patients cleared three quarters or more of their lesions (p<0.0001) and in the lowest dose group, 56% of patients cleared three quarters or more of their lesions (p=0.0002). Patient assessments of convenience and ease of use, healing time, cosmetic outcome, satisfaction compared to prior AK treatment and overall patient satisfaction with PEP005 Topical for AK were positive. Principal investigator Lawrence Anderson MD of Tyler, Texas said the results point to a product that could potentially address an important unsatisfied medical need in the treatment of AK.
“The ability to treat AK with a short two or three Peplin CEO Michael Aldridge said these results built upon those delivered in
previous Australian and US AK clinical studies. “In particular we were pleased to demonstrate statistically significant complete and partial AK clearance rates. We believe these will be the efficacy measures for our phase III clinical studies for US regulatory approval.”
Sydney dermatologist Dr Robert Rosen, who has served as an investigator on other Peplin AK clinical studies said the results were impressive with respect to their consistency regarding safety and efficacy.
“The goal of AK treatment is to clear the lesions and thus reduce the potential for the development of skin cancer. In view of the patient satisfaction with treatment outcomes in this study, this product may provide an attractive, patient friendly and convenient treatment alternative.”
Peplin intends to discuss the results of this trial with the FDA, together with interim results of its ongoing PEP005-007 facial AK clinical trial, pre-clinical, manufacturing and other data. Peplin also intends to present plans for a phase III clinical program and other studies required to support a new drug application (NDA) of PEP005 Topical for AK. Peplin anticipates initiating the first clinical study of its phase III clinical program in the first quarter of 2008. Details of the PEP005-006 clinical trial are set out below
The clinical trial (PEP005-006) is a multi-centre, randomised, double-blind, double-dummy, vehicle-controlled study designed to evaluate the safety and efficacy of PEP005 Topical for AK in patients with actinic keratosis lesions. Treatment with PEP005 Topical for AK was evaluated at three dosages: a concentration of 0.025% for three consecutive days and a concentration of 0.05% administered for two or three consecutive days. Medication was applied to a 25 cm2 contiguous area of skin containing 4 to 8 AK lesions on the arm, shoulder, chest, back or scalp. The study was conducted under Peplin’s Investigational New Drug (IND) application with the FDA. The study objectives were to:
1. evaluate the safety and tolerability of PEP005 Topical for AK; and
2. evaluate the efficacy of PEP005 Topical for AK.
The primary efficacy measure was the partial clearance rate:
• Partial clearance rate (PCR) is defined as the proportion of patients who, on the 57th day post-treatment, manifested 75% or greater reduction in the number of AK lesions identified at baseline in the treatment area. Lesions that are not present at the baseline measurement but that manifest during the course of treatment do not affect this measurement.
Two secondary measures of efficacy were also evaluated:
• Complete AK lesion clearance rate (CCR) defined as the proportion of patients who, on the 57th day post treatment, manifested no clinically visible AK lesions in the treatment area, whether they existed at the baseline measurement or manifested during the study period.
• Baseline AK lesion clearance rate (100% CR) defined as the proportion of patients who, on the 57th day post treatment, manifested 100% reduction in the number of AK lesions identified at baseline in the treatment area. Lesions that are not present at the baseline measurement but that manifest during the course of treatment do not affect this measurement.
Description of trial subjects
A total of 283 patients were screened into the study, with 222 patients meeting the eligibility criteria and subsequently randomised to treatment with PEP005 Topical for AK or vehicle gel. All 222 patients enrolled in this study were Caucasian, with 3 patients (1.4%) of Hispanic ethnicity. The age range of patients was 43 to 85 years, with a mean age of 67.0 years. The majority of patients 178 (80.2%) were male and 152 (68.5%) had Fitzpatrick-Pathak skin types 1 or 2 (burn easily and tan rarely or minimally).
Patients were randomised to one of three active treatment groups or a vehicle treatment group in the ratio of approximately 3 to 1. The three active treatment groups comprised:
1. 0.025% PEP005 Topical for AK on days 1, 2 and 3 (50 patients);
2. vehicle on day 1 and 0.05% PEP005 Topical for AK on days 2 and 3 (55 patients); or
3. 0.05% PEP005 Topical for AK on days 1, 2 and 3 (57 patients).
The vehicle treatment group (60 patients) received vehicle gel on days 1, 2 and 3. Study drug or vehicle from single use mini-tubes was applied by the patient (the first under physician supervision) to the defined 25 cm2 treatment area once daily for three consecutive days.
The third dose was applied, as directed, following the first post-treatment physician visit.
Safety: The drug suggested a favourable safety profile and was well tolerated by patients at all dosages. There were no serious adverse events (SAEs) related to study medication. The most common side effects were localised skin responses comprising erythema (redness), flaking or scaling and crusting in the treatment area. Local skin responses resolved spontaneously and generally within two to four weeks of treatment. Across all active treatment groups, 24 patients (of a total of 159) were reported not eligible to apply the third day dose due to response to drug.
On a global severity rating scale of none, mild, moderate and severe the majority of global responses were graded as either mild or moderate in all treatment groups, with approximately 20% of the highest dosage treatment group graded as severe.
The study suggested a clear dose response on all three efficacy measures. Efficacy in terms of the PCR, CCR and 100% CR is presented on a modified Intent to Treat (mITT) basis. The mITT population consists of all patients who received at least one dose of medication and had at least one post baseline assessment. The statistical significance of the difference in clearance rates of active treatment groups compared to vehicle treatment groups is presented in terms of the p value in the chart below.
*** SEE ATTACHMENT FOR CHART***
Peplin believes the PEP005-006 study demonstrates a potentially safe and effective new short course field-directed therapy for AK on non-facial sites. In parallel with this study Peplin is conducting an Australian and New Zealand clinical study, PEP005-007. The PEP005-007 clinical study is an open label phase IIa study designed to evaluate the safety and efficacy of PEP005 Topical for AK at various formulation strengths when applied as a field-directed therapy to areas on the face and scalp.
Peplin intends to meet with the FDA and discuss the results of the PEP005-006 trial, interim results of the ongoing PEP005-007 clinical trial, pre-clinical, manufacturing and other data. Peplin expects to present the FDA plans for a phase III clinical program and other studies
required to support an NDA for PEP005 Topical for AK. Subject to input from FDA, Peplin anticipates initiating the first clinical study of its phase III clinical program in the first quarter of 2008.
ABOUT ACTINIC KERATOSIS
AK is generally considered the most common pre-cancer. AK usually appears as small, rough, scaly areas of skin on the face, lips, ears, back of hands, forearms, scalp or neck, areas that are most commonly exposed to the sun. If left untreated up to 5% of AK lesions may progress to a form of skin cancer called squamous cell carcinoma.
The treatment of AK lesions is the most common dermatologic procedure performed in the outpatient setting. Based on a 2005 study by The Lewin Group, Inc., there were 58 million Americans living with AK, there were 8.2 million office visits in 2004, with a cost to the US
healthcare system of US$1.2 billion. In northern hemisphere populations, 11% to 25% of adults have at least one AK lesion, compared
with 40% to 60% of adults in Australia, which has the highest prevalence of AK worldwide.
Peplin is a specialty pharmaceutical company focused on the development and commercialisation of innovative medical dermatology products. Peplin was founded in 1998 to research and develop a new class of compounds that are naturally occurring and have the potential to treat certain cancers and pre-cancerous conditions, including skin cancer and precancerous lesions, while minimizing some of the limitations associated with existing treatment alternatives. These compounds are small molecules purified from the sap of Euphorbia peplus, or E. peplus, a rapidly growing, readily-available plant commonly referred to as petty spurge or radium weed. E. peplus has a long history of traditional use for a variety of conditions, including topical self-treatment of various skin disorders.
Chief Executive Officer
Tel: +1-510 653 9700 (US)
Tel: +61-7-3250 1200 (AUS)
Hill & Knowlton
Tel: 02-9286 1272 / 0408 321 312
Posted: July 2007