Combination therapy shows promising phase 2 results

Jul 28, 2016, 4:00am

Data suggest photodynamic therapy with the investigational topical methyl aminolevulinate may be an effective treatment for patients with severe facial acne.

A 12-week phase 2 study of 153 patients with severe facial acne suggests those using photodynamic therapy (PDT) with the investigational topical methyl aminolevulinate, or MAL, (Photocure ASA) had significantly reduced inflammatory acne lesion counts compared to PDT and vehicle.

PDT treatment with the photosensitizer MAL, 80 mg g−1, reduced acne lesions by an average 15.6 compared to 7.8 in the control group. That’s a percentage change of 37.3 percent in the active group, versus 16.2 percent among controls.

The decrease in noninflammatory lesions wasn’t significant in the two groups. And PDT/MAL treatment resulted in manageable pain and erythema comparable to the control group, according to the study.

This is a promising finding for patients with moderate to severe acne, according to the study’s lead author David M. Pariser, M.D., professor of dermatology at Eastern Virginia Medical School, Norfolk, Virginia, and past president of the American Academy of Dermatology.

Dr. Pariser“There have been a lot of attempts at using PDT for treatment of acne, particularly the severe acne, which is usually managed by antibiotics or even systemic use of isotretinoin,” he says. “This is among the first prospective controlled trials of acne treatment versus placebo treatment, where we were really able to demonstrate clearly over placebo the effect of [PDT] treatment.”

While MAL is an investigational drug, not yet available in the United States but widely used in Europe, there are PDT agents that are available in the United States for treatment of actinic keratoses. Levulan (aminolevulinic acid (ALA) HCl, Dusa) is one. And Ameluz (ALA, hydrochloride, Biofrontera Pharma) was FDA approved in May 2016 for treatment of actinic keratoses. The Leverkusen, Germany-based pharma company announced May 11, 2016 that the FDA approved its combination topical prescription drug Ameluz (BF-200 ALA) and medical device BF-RhodoLED for PDT treatment of mild to moderate AK on the face and scalp.

The way a PDT agent works in acne is the drug, when applied to the skin’s surface, is absorbed preferentially in sebaceous glands. When in those cells, it converts to protoporphyrin IX. Then, when exposed to a bright light of a certain wavelength, a photochemical reaction occurs, destroying the cell in which the drug has been absorbed, according to Dr. Pariser.

“The light, by itself, doesn’t do much of anything; the drug, by itself, doesn’t do anything. The combination is what works,” Dr. Pariser says.

NEXT: Future application

 

Future applications

Completion of a phase 3 trial and potential FDA approval for MAL in the treatment of acne could be years away, but the fact that there is are similar drugs on the market for a different indication means that doctors are and will use those, off label, for acne treatment, Dr. Pariser says.

Dr. Pariser says that he sees PDT with MAL as a potential option in treatment of moderate to severe acne. The drug didn’t work on noninflammatory acne, he says, because there are no abnormal skin cells in the noninflammatory lesions to attract the topical. Noninflammatory lesions are just blocked pores, basically.

“We have plenty of treatments for mild to moderate acne, including many different topical agents, which are pretty effective,” he says. “For moderate acne, we generally use systemic antibiotics. But there has been a move in general medicine to try to get away from overuse of systemic antibiotics, where possible. So, this treatment would provide a potential option there, but it really isn’t proven yet.”

The other place for MAL might be in patients with severe acne who don’t respond to systemic antibiotics and who generally go onto using an isotretinoin.

“That’s a very heavy duty drug with lots of hassles in terms of the iPLEDGE program to prescribe,” Dr. Pariser says. “If this new PDT treatment were to work well enough, it may prevent some patients from having to go onto the more involved treatment of isotretinoin, more hassle and more toxicity.”

Still, PDT for acne is not there yet, according to Marisa Taylor M.B.B.S., M.Sc., a doctor of medicine (dermatology) in Wales, UK, who wrote the accompanying commentary “Photodynamic therapy for acne: are we there yet?” in the April issue of the British Journal of Dermatology.

“…we aren't there yet with regards to recommending a reproducibly successful, efficacious regime in the use of photodynamic therapy for acne. But, as stated in my commentary, if dermatologists seek to focus on refining the questions asked of this treatment, I am sure a clinically useful evidence-based consensus can be made,” Dr. Taylor tells Dermatology Times.

Disclosure: Dr. Pariser has been a consultant and researcher for Photocure, as well as a consultant for Dusa and Biofrontera Pharma. Dr. Taylor reports no conflicts. This study was funded by Photocure ASA.

References:

Pariser, D.M., Eichenfield, L.F., Bukhalo, M., Waterman, G., Jarratt, M., the PDT Study Group (2016), Photodynamic therapy with methyl aminolevulinate 80 mg g−1 for severe facial acne vulgaris: a randomized vehicle-controlled study. British Journal of Dermatology, 174: 770–777.

Taylor M. Photodynamic therapy for acne: are we there yet? Br J Dermatol. 2016 Apr;174(4):712-3.