Although it has been used off-label for decades, the photosensitizing agent aminolevulinic acid (ALA) hydrochloride could see greater uptake in the wake of the FDA approval of Biofrontera’s Ameluz for superficial basal cell carcinoma (BCC), said dermatologists.

The agency approved Ameluz (ALA hydrochloride) topical gel, 10%, used with Biofrontera’s BF-RhodoLED lamp, for treating superficial BCC in adults — making this the first photodynamic therapy (PDT) drug approved in the US for skin cancer. It has been approved for the treatment of actinic keratoses since 1999.

ALA-based PDT is a go-to skin cancer treatment in many other nations — in South America and Europe and other regions — where Mohs surgeons are not as prevalent.

Having FDA approval for BCC is key to securing insurance coverage, but it also gives the treatment “even more substantiated validity,” Anthony Rossi, MD, attending dermatologist at Memorial Sloan Kettering Cancer Center in New York City, told Medscape Medical News.

“We’ve always used [PDT] in difficult cases,” said M. Shane Chapman, MD, MBA, chair and professor in the Department of Dermatology at Dartmouth Hitchcock Medical Center in Lebanon and the Dartmouth Geisel School of Medicine in Hanover, New Hampshire. The approval provides outcomes data and reassurance, said Chapman, who was an investigator on Biofrontera’s pivotal phase 3 trial.

Ameluz PDT is “going to be a great FDA-approved option going forward,” especially for patients who can’t or would prefer not to undergo surgical removal, Chapman told Medscape Medical News.

‘Elegant’ Therapy

Rossi calls Ameluz an “elegant therapy” that precisely targets cancerous cells. ALA is made in blood and “gets preferentially taken up into more metabolically active cells such as precancers or skin cancers,” he said. It is converted to protoporphyrin IX, a photosensitizing factor that creates reactive oxygen in response to the red light, killing the atypical cells.

In Biofrontera’s pivotal double-blind, randomized, placebo-controlled phase 3 study, 66% (n = 95) of the patients who received the therapy achieved the primary endpoint: a composite of clinical and histologic complete response of the main target lesion 12 weeks after the start of the last PDT cycle.

According to the FDA label, all trial participants had at least one adverse reaction at the application site, with the most common being application site pain that may be severe, erythema, pruritus, edema, paresthesia, scab, induration, and exfoliation.

The label also advises against use around mucous membrane areas.

Rossi said he has used PDT “in almost every part of the body,” including the genital mucosal areas, because it is less invasive and many patients prefer not to have surgery on their genitals if it’s not necessary. If a lesion is “superficial and very early, you have this option, and we’re not losing control of the disease because we’re going to keep following you,” he said.

Chapman also generally does not restrict use. Often, “where we’re going to use photodynamic therapy are in places where you don’t want to have surgery,” which might include near an eyelid or around the lip, he said.

Many May Choose Nonsurgical Option

Rossi said patient selection and assessing tumor biology are important, noting that PDT might not be able to reach some BCCs that have a deeper component.

For patients with BCC, he engages in shared decision-making, he said. “Some patients really do have anxiety about the word cancer, even if it’s a very early cancer or a low-risk cancer like a basal cell or a superficial basal cell, and they want to know that it’s completely out, so they choose surgery,” he noted.

Others may want to avoid scars or have fears about surgery and will elect PDT, Rossi said.

The FDA label describes a lengthy treatment process, including a 3-hour period for Ameluz to be taken up before the red light is applied. It may take multiple treatments.

“It’s not usually a one-and-done,” Rossi said.

Chapman said he usually employs an incubation period of 30 minutes to 1 hour, followed by 10-15 minutes under the light. The total time is comparable to that of a Mohs procedure, he said.

He has used Ameluz off-label in immunocompromised patients — including those who have had solid organ transplants or are living with chronic lymphomas and leukemias. Those patients are vulnerable to BCC and may have multiple lesions at once, requiring many Mohs procedures.

“They get tired of the bandages, and the wounds, and the procedures,” Chapman said.

Another group of patients susceptible to multiple BCCs — those with hereditary Gorlin syndrome — will also benefit from Ameluz, and finally, some patients just don’t want surgery, he said.

Chapman reported having no relevant disclosures. Rossi reported being a consultant for Biofrontera and Sun Pharma, which makes a competing PDT for actinic keratoses.

Alicia Ault is a St. Petersburg, Florida-based freelance journalist whose work has appeared in many health and science publications, including Smithsonian.com. You can find her on X @aliciaault and on Bluesky @aliciaault.bsky.social.