Treatment Pipeline for Rosacea

Linda Stein Gold, MD, presented the session, “Rosacea: What’s New and What’s Coming,” at Dermatology Week 2022, with a review of rosacea pathogenesis and a discussion of novel topical and systemic treatment approaches.

“In order to understand the best treatment options, it’s important to understand the pathogenesis of the disease,” Dr Gold began. “When we think about the treatment options, often patients manifest with a number of different signs and symptoms of rosacea, so often we’ll mix and match treatments in order to really get a more comprehensive approach to treatment.”

She explained how mast cells are increased in the dermis of patients with rosacea, “This is a cell that has a lot of different properties and potentially could be a target of treatment that would help in the underlying pathogenesis of the disease.”

Dr Gold spoke about how rosacea is “characterized by severe skin dryness, elevated pH, trans-epidermal water loss, and decreased hydration levels.” She stated, “We have to pay attention to repairing the skin barrier in any treatment regimen we put in place for our rosacea patients.”

She then delved into what is new and what is coming in rosacea treatment, “When we look at antibiotics for the treatment of rosacea, you might think, ‘Why does this make sense?’ When we look at the properties of minocycline, we find that minocycline has been shown to decrease LL-37 and we know LL-37 is central to the pathogenesis of rosacea.” Tetracycline antibiotics are associated with numerous nonantibiotic properties that are important for rosacea pathophysiology, including decreasing inflammation.

Dr Gold indicated that “minocycline is a large molecule that is challenging to deliver topically;” however, there is a minocycline foam 1.5% available. This foam was studied in 1522 patients with moderate to severe papulopustular rosacea using it once a day for 12 weeks. “The proportion of patients achieving IGA [Investigator’s Global Assessment scale] treatment success in both treatment groups was statistically significant as compared with [the] vehicle at week 12,” she reported. The drug was well-tolerated and “any hyperpigmentation that was seen was thought to be post-inflammatory hyperpigmentation.” An open-label, 40-week extension study was also conducted, which showed no serious treatment adverse events.

Low-dose oral minocycline has shown early treatment success at week 4 in a phase 2, randomized trial, with statistically significant results for the 40-mg, extended-release dose. This dose “had the highest improvement in quality of life as compared with the other treatments [trialed],” Dr Gold pointed out.

She asked the question: Is low-dose minocycline antibacterial? Plasma levels remain below the minimum inhibitory concentration. “That’s good news because it tells us there’s a good likelihood that this drug might be just anti-inflammatory and hopefully not antimicrobial as well,” she remarked.

Dr Gold also asked: Can we use benzoyl peroxide (BPO) to treat rosacea? “Microencapsulation stabilizes the BPO and reduces direct exposure to the skin, theoretically reducing irritation,” she noted. Microencapsulated BPO (E-BPO) was studied in adults ages 18 and older who had moderate to severe rosacea using it once daily for 12 weeks. The findings showed 50% of patients getting to clear, with an improvement being seen as early as week 2 and an increase in skin tolerability using 5% E-BPO.

Oral sarecycline, which is FDA approved for the treatment of acne, has also been studied for patients with papulopustular rosacea. After taking the sarecycline as monotherapy once daily for 12 weeks, 75% of patients got to clear or almost clear at week 12. And sarecycline does not appear to cross the blood-brain barrier.

“The bottom line is, it’s really an exciting time for rosacea [and] there is an active treatment pipeline. Aim for clear skin!” Dr Gold concluded.

Reference

Gold LS. Rosacea: what’s new and what’s coming. Presented at: Dermatology Week 2022; May 11–14, 2022; Virtual.