Positive Preliminary Results of Phase IIb AK Study
• Statistically significant lesion clearance at all
doses
• 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).
Treatment method
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.
Preliminary results
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.
Efficacy:
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***
Implications
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.
ABOUT PEPLIN
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.
Further information:
Michael Aldridge
Chief Executive Officer
Tel: +1-510 653 9700 (US)
Tel: +61-7-3250 1200 (AUS)
michael.aldridge@peplin.com
Media:
Tim Mullen
Hill & Knowlton
Tel: 02-9286 1272 / 0408 321 312
tmullen@hillandknowlton.com.au
Posted: July 2007
