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In the pipeline: Researchers look for imiquimod alternatives


Although Aldara (imiquimod, Graceway) is effective treatment for basal cell carcinomas and actinic keratosis, researchers are looking for alternative topicals with fewer drawbacks.

Key Points

In Omaha, Neb., Joel Schlessinger, M.D., a medical/aesthetic dermatologist who participates in clinical trials, says a number of imiquimod alternatives are at various stages in the pipeline, and we may be looking at combinations of medications in the future, rather than a single drug approach.

"The most obvious alternative will be a generic version of Aldara. Aldara has been on patent for enough time that generics are being developed," Dr. Schlessinger tells Dermatology Times.

"Aldara's cure rate ranges from 80 to 85 percent, versus 90 to 98 percent for excision and/or Mohs surgery. As a result, it's usually considered a back-up method of treatment for skin cancers, rather than the treatment of choice. There is hope that resiquimod will be a more potent, reliable form of the medication," he says.

Dr. Schlessinger says that researchers and physicians also hope to find a therapy that can be fully effective in a shorter period of time.

"Aldara is used for several conditions, and the official dosage regimen for actinic keratosis is two times a week for five weeks; for superficial BCC, it's five times a week for six weeks; while for genital warts, the dose is three times a week for 16 weeks. So, we have a multitude of treatments, but they all take time," he says.


One medication that could be effective much more quickly is under investigation by Peplin, a pharmaceutical company based in California and Australia.

PEP005 gel (ingenol mebutate) comes from a common plant, Euphorbia peplus, known as petty spurge or radium weed. The sap has long been used as a traditional approach to treating various skin lesions, including cancer and AK.

"Initially, PEP005 rapidly induces necrosis, resulting in the debulking of locally affected tumor cells. Then, it induces a tumor cell-specific innate immune response which results in a removal of residual disease," says Peter Welburn, Ph.D., Peplin's chief scientific officer.

Peplin recently completed enrollment in its first phase 3 trial for lesions on nonhead locations using a 0.05 percent dose applied once daily for two days. The company announced additional phase 3 trials would use a dose of a 0.015 percent concentration of PEP005 gel applied once daily for three consecutive days for the treatment of actinic keratosis on the head.

Peplin plans to file a new drug application by mid-2010.


Another option - a pain reliever - also offers some potential for the treatment of skin cancer and pre-cancerous lesions.

According to Dr. Schlessinger, Voltaren (diclofenac), a nonsteroidal anti-inflammatory drug better known in its oral form for relieving pain of arthritis, may be effective with actinic keratoses.

"For our purposes, in a gel form, when topically applied, it's believed that diclofenac may work via decreased prostaglandin synthesis in the skin," he says.

Aldara drawbacks

"One big challenge we face is determining whether a carcinoma or precancerous lesion has been fully treated by Aldara," Dr. Schlessinger says.

"Unfortunately, with Aldara, we find that 20 percent of the time, what appears to have been successfully treated has actually not been completely removed and we get a false negative, so treatment may be terminated too soon," he says.

False-positive readings are also possible. Although less common, he says they can lead to additional, unnecessary treatment.

"The key to success in this area is finding the 'sweet spot' where treatments are effective and results are predictable with little or no irritation and maximal benefits. It may be that over time we combine certain compounds to harness the best of these drugs and alleviate some of the less desirable side effects," Dr. Schlessinger says.

Disclosures: Dr. Schlessinger has been an investigator for 3M, Graceway, Tolmar and Peplin.

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