CHICAGO — Topical therapy for 2 or 3 days with the investigational agent ingenol mebutate, also known as PEP005, provides substantial clearance of actinic keratosis lesions, according to findings from two phase II randomized studies.
"A comparison of efficacy outcomes with those of studies of diclofenac, 5-FU [fluorouracil], and imiquimod shows at least equivalent clearance of lesions over a much shorter period," Dr. Lawrence Anderson, one of the current study's lead investigators, reported at the American Academy of Dermatology's Academy 2008 meeting.
Ingenol mebutate gel has the potential to enhance compliance not only by its shorter course of therapy, but also by the truncated period of irritation in patients with actinic keratosis (AK), the investigators suggested.
PEP005 is a new class of compound derived from the sap of Euphorbia peplus, a readily available plant that has been used in Australia for centuries as a traditional treatment for skin conditions. The two current studies were sponsored by Peplin Ltd. of Brisbane, Australia, which is developing PEP005.
Dr. Anderson, who is in private dermatology practice in Tyler, Texas, and his associates randomized 222 patients with 4- 8 visible AK lesions on the arm, shoulder, chest, back, or scalp, to one of four treatment groups. The primary end point was partial clearance, defined as the proportion of patients at day 57 with 75% reduction in the number of AK lesions identified at baseline.
Treatment with PEP005 gel once daily for 2 or 3 days produced significantly greater lesion clearance in a dose-dependent manner by all measures and at all dosing regimens, compared with a control vehicle applied once daily for 3 days.
The partial clearance rate was 22% for vehicle, 56% for ingenol mebutate gel 0.025% for 3 days, 62% for ingenol mebutate gel 0.05% for 2 days, and 75.4% for ingenol mebutate 0.05% for 3 days.
The proportion of patients at day 57 with complete clearance, defined as no clinically visible AK lesions, was 12%, 40%, 44%, and 54.4%, respectively.
All three active treatments were well tolerated, according to the investigators, one of whom was a Peplin employee. The most common lesion-site reactions on day 57 were erythema, experienced by 34% of 162 actively treated patients; flaking or scaling (29%); and crusting (9%).
Because AK lesions on the trunk and extremities historically are more difficult to treat than scalp lesions, the investigators performed an ad hoc analysis to compare outcomes in patients with scalp and nonscalp lesions, Dr. Michael Freeman of the Skin Centre, Gold Coast, Australia, and his associates said in a separate poster.
Overall, scalp treatment areas had a higher complete clearance rate than nonscalp treatment areas (57% vs. 42.4%), although the gel was better tolerated when applied to nonscalp areas, regardless of concentration or dosing schedule, the investigators wrote.
The maximum tolerated dose (MTD) for face or face and scalp AK was determined to be once-daily ingenol mebutate gel 0.025% for 2 days, according to a second study that evaluated six formulation strengths ranging from 0.0025% to 0.025% in 86 patients with lesions limited to the face or face and scalp.
At the MTD, 26 of 36 patients (72%) achieved partial clearance and 14 of the 36 (39%) achieved complete clearance.
Ingenol mebutate gel was well tolerated across all strengths, with erythema the most common lesion site reaction. Three patients experienced four serious adverse events, none considered treatment related, according to the investigators, one of whom was also a Peplin employee.
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