Striking gold for AKs?: Trials show ingenol mebutate is a safe, effective, extremely rapid treatment

November 1, 2008

Ingenol mebutate is taking the dermatology world by storm as it time and again proves its high efficacy and excellent safety profile in the treatment of AKs. Many dermatologists are eagerly awaiting FDA approval of this novel topical therapy in the United States.

Key Points

"Ingenol mebutate offers patients with AKs a very simple solution, as the treatment course is only two to three days long and, until now, this seemingly revolutionary topical therapy has been very successful in treating these lesions. Furthermore, the safety profile of ingenol mebutate to date has been excellent," says Lawrence Anderson, M.D., F.A.C.P., Dermatology Associates of Tyler, Tyler, Texas.

Studies have shown that patients who previously were treated with other topical modalities prefer to be treated with ingenol mebutate gel. Dr. Anderson tells Dermatology Times that though very effective, an Efudex (fluorouracil, Valeant) treatment course can last many weeks, making it somewhat challenging for patients to strictly comply with the protocol, particularly because they will likely experience significant local skin responses (LSR) throughout the lengthy period.

Different concentrations

Dr. Anderson headed a recent study aimed at evaluating the efficacy and safety of two concentrations of ingenol mebutate (0.025 percent and 0.05 percent) for treating nonfacial AKs. In the double-blind, double-dummy, vehicle-controlled, 57-day study, 222 patients were randomized to receive either a once-daily (QD) treatment with vehicle on days one, two and three; ingenol mebutate gel, 0.025 percent, on days one, two and three; vehicle on day one and ingenol mebutate gel, 0.05 percent, on days two and three; or ingenol mebutate gel, 0.05 percent, on days one, two and three.

Efficacy of the treatment was assessed by rates of partial clearance (patients with =75 percent reduction in baseline AK lesions in the treated area), complete clearance (patients with no clinically visible AK lesions in the treated area), baseline clearance (patients with 100 percent reduction of baseline AK lesions in the treated area) and median reduction in baseline lesions. Results showed that all three active treatments were significantly more effective than vehicle in reducing the number of AK lesions at day 57 by partial, complete and baseline clearance rates. Dr. Anderson says both 0.025 percent and 0.05 percent doses were effective for AK lesions on nonfacial sites.

The data showed that patients tolerated the treatment very well. Dr. Anderson says the LSRs were significant and included erythema, flaking, scaling and vesiculation, as well as pustulation and erosion, but these sequelae usually resolved within the first two weeks after treatment. No scarring or any significant hypo-or hyperpigmentation occurred.

New gold standard?

"In my opinion, the current gold standard for field treatment of AKs would be 5-fluorouracil and/or imiquimod. If the clinical data holds through the currently ongoing phase 3 trials, this may very well become the gold standard, as the treatment requires fewer applications, a shorter period of time and more rapid resolution of side effects, with at least as good or better efficacy," Dr. Anderson says.

Ingenol mebutate was developed in Australia in the late 1990s, and if all goes well with the current FDA phase 3 trial for nonface applications and the phase 3 trials for face and scalp applications slated to begin early next year, the treatment may soon be available in the United States.

Imiquimod is currently being used for superficial BCCs and SCCs, so, theoretically, ingenol mebutate may also be tried for these skin cancers. Dr. Anderson says that given the nature of the cellular necrosis mechanism of this drug, it may actually prove to be an even more efficient therapy in thicker tumors than other topicals, such as imiquimod.

"The clinical data to date has been extraordinary, and if the drug does well in the phase 3 trials, I see ingenol mebutate becoming the treatment of choice for AKs. I believe that the drug has enormous potential to topically treat a variety of other skin conditions that have been challenging to treat to date with other topicals," Dr. Anderson says.

Disclosure: Dr. Anderson has been a clinical investigator for Peplin on the studies mentioned in this article. He is also on the Peplin Strategic Advisory Board and has served as the chairman of some Dose Escalation Study committees.

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