Conference Coverage

Products being developed for AKs therapy may appeal to patients


 

REPORTING FROM CARIBBEAN DERMATOLOGY SYMPOSIUM

– It’s unanimous: Patients with actinic keratoses (AKs) want them to go away quickly, painlessly, and pretty much invisibly. In fact, they’d rather risk developing cancer than deal with weeks of painful, red, oozing crusts.

But unless Ronco comes up with the AK-Away Wand, dermatologists and patients have to face facts, Theodore Rosen, MD, said at the Caribbean Dermatology Symposium, provided by Global Academy for Medical Education.

“Some AKs are going to just go away, and some are going to just sit there unchanging. Not all AKs are going to turn into squamous cell cancer. But you can’t tell which ones will, and because you can’t predict, they should all be treated. It’s our job to make patients care about this.”

That job starts with the very first conversation, said Dr. Rosen, professor of dermatology, Baylor University, Houston. “The way you frame the information at the very beginning is so important. You have to get the word ‘cancer’ in there.”

Most patients don’t fully grasp the serious threat that a transformed AK can pose, as illustrated by a survey of patients at the Milton S. Hershey Medical Center in Hershey, Pa.. The survey also highlighted the importance of the first discussion with the physician. Almost 550 dermatology clinic patients completed the survey, which presented five AK treatment decision scenarios, asking patients how likely they would be to pursue treatment in each situation (JAMA Dermatol. 2017;153[5]:421-6). Each scenario was factual, but the emphasis on facts varied. The first four questions characterized the lesions as sun damage and stressed the low incidence of malignant transformation (0.5%), and the large percentage that remain unchanged (75%) and spontaneously disappear (25%).

The last question was much simpler and more direct: “Actinic keratoses are precancers. Based on this statement, how likely are you to want treatment?”

“When AK was presented without the word ‘cancer’ in the description, there were lower proportions of individuals who said they would want to receive treatment [about 60%],” Dr. Rosen said. “Presenting AK as a precancer had the highest proportion of patients saying they would prefer treatment – about 92%.”

But current treatments aren’t ideal, at least from the standpoint of patients who prefer fast results with a minimum of erythema, oozing, crusting, and pain. Dr. Rosen looked into his crystal ball and saw a few encouraging treatment options coming down the drug development pike. To make it past regulatory hurdles, though, any new treatment has to hit the sweet spot of approximately 80% lesion clearance, with less than 40% recurrence at 1 year. Whether these investigational protocols can complete that journey remains to be seen.

VDA-1102

VDA-1102, in an ointment formulation, is based on a stress response chemical found in the jasmine plant. It contains a synthetic derivative of methyl jasmonate, a plant stress hormone found in jasmine. According to the patent record for VDA-1102, jasmonates are released in extreme ultraviolet radiation, osmotic shock, heat shock, and pathogen attack to initiate injury response and repair cascades.

The drug stops tumor growth by inhibiting glycolysis; it removes hexokinase 2 (HK2) from mitochondria. HK2 is found only in malignant cells; normal cells have the hexokinase 1 variant. Hexokinase is a key modulator of the transformation of adenosine triphosphate to adenosine diphosphate. As an HK2 modulator, VDA-1102 should, therefore, only induce apoptosis in the malignant cells, Dr. Rosen said.

“In preclinical studies in a hairless mouse model, they were approaching that 80% mark with lesion regression.” But the drug doesn’t induce necrosis or inflammation – a huge plus for patients. “There’s almost nothing in terms of redness, scaling, inflammation, or pain. This could be a really attractive addition to the AK toolkit. Improved aesthetics during treatment translates into improved patient willingness to undergo recurrent treatments. It may also be useful for treating large fields of AK, and in immunosuppressed patients.”

An Israeli company, Vidac Pharma, is conducting a phase 2b study of 150 patients with AK. The big question? Duration of effect – something that can’t be determined in the 21-week study. The company is aiming to launch a phase 3 trial next year.

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