While many are in early phase studies, most of the new topical options are targeting sebum reduction, a novel pathway to controlling acne, and the data are exciting, one expert says.
New and emerging prescription topical and over-the-counter acne treatments offer a new drug target, better penetration of the active drugs and, potentially, better outcomes than traditional acne treatment options, according to Leon H. Kircik, M.D., clinical associate professor of dermatology at Indiana University School of Medicine, Louisville, Ky.
Dr. Kircik spoke on the topic of emerging therapies at the Orlando Dermatology Aesthetic and Clinical Conference (Orlando, Fla., January 2016).
Dr. KircikRecent research on severe and moderate acne patients with inflammatory acne helps to confirm the strength and efficacy of fixed dose combination gel adapalene/benzoyl peroxide 0.3%/2.5% (Epiduo Forte, Galderma), according to Dr. Kircik.
The once-daily topical’s phase 3, multicenter, randomized, double-blind, 12-week study included 50% severe and 50% moderate patients. Among the study’s findings: Epiduo Forte demonstrated superiority in the overall study population at 33.7% versus 11.0% for placebo gel at week 12 for the Investigator’s Global Assessment (IGA) Success Rate and for changes in inflammatory (-68.7% vs -39.2% ) and non-inflammatory lesion count (-68.3% vs -37.3% ). To be considered treatment successes, subjects who were severe at baseline had to finish the 12 weeks at clear or almost clear.
It’s not an easy task for any acne drug, according to Dr. Kircik.
“When you look at the IGA scale, it’s a very high bar that was put up by the FDA,” Dr. Kircik says. ”If you start severe, you have to become almost clear, and that means you have a three-grade improvement. If you start moderate, you have to be at least almost clear and have a two-grade improvement.”
Many of the patients in the study were so severe, according to Dr. Kircik, that dermatologists might want to start them on isotretinoin.
“In the study, the mean inflammatory lesion count was about 38 and noninflammatory was about 59. Average total lesion count was close to 100,” Dr. Kircik says. “I’ve done a lot of clinical studies but [this study had particularly high lesion count numbers]”.
The result: Inflammatory lesion count reduction was about 68%.
“Now, this is on the overall population, both severe and moderate,” Dr. Kircik says. “What’s impressive here, when you look at the severe population, the mean percent decrease in inflammatory lesion count was about 72% at twelve weeks.”
Even the patients in the study who were considered treatment failures by FDA standards would be happy patients, according to Dr. Kircik. The dermatologist explained IGA always trails lesion reduction.
“The problem with the IGA scale is the overall impression is very subjective, unlike the lesion count, which is objective. Here there is no counting. You walk in and look at the patient and make a decision: moderate, mild, severe. FDA tells us you cannot count the lesions. You have to do the IGA first; then, you count the lesions,” he says.
One OTC product that appears to show efficacy in studies is a combination of lipohydroxy acid (LHA) and micronized benzoyl peroxide (BP) (Efficlar Duo, La Roche Posay). The combination penetrates the pilosebaceous unit, which is where BP, alone, falls short.
“As we all know, BP is a great antimicrobial. It’s a great anti-comedogenic, anti-keratolytic, as well as anti-inflammatory. So, BP does a lot of heavy lifting in acne treatment,” he says. “But if you buy the BP from Walgreens or CVS, it’s going to sit on the skin and crystalize. It’s not going to go anywhere, unless you have a nice vehicle. If you don’t, it’s going to irritate the patient.”
LHA, he says, is a derivative of salicylic acid. The LHA molecule has been found to separate transmembrane glycoproteins at the corneosome/corneocyte, cleanly detaching individual corneosomes from one another. It also has antimicrobial and anti comedogenic effects.
Researchers were “gutsy,” Dr. Kircik says, and studied Efficlar Duo against a combination of 5% BP and clindamycin. The treatment regimen was either Efficlar Duo in the morning with a retinoid .025% in the evening versus the market leader of benzoyl peroxide 5% with clindamycin in the morning and retinoid .025% in the evening.
“Guess what? This was a [12-week] non-inferiority study and this product did as well as the prescription regimen. Really, sometimes, simple things work, as well as the prescription product…,” Dr. Kircik says.
On the horizon, there’s BPX-01. Dermatologists are familiar with oral minocycline but topical minocycline has been difficult to stabilize and it’s a very lipophilic product, according to Dr. Kircik.
The drug’s maker overcame the challenge by putting minocycline in a hydrophilic environment. Once it’s applied, it goes back to its original lipophilic state, then, gets absorbed into the pilosebaceous unit where the action takes place.
“That’s where you need your medication. This is the first stable hydrophilic topical minocycline. This is very early phase. The studies are just going to start,” Dr. Kircik says.
Preclinical data show delivery of minocycline directly to the epidermis and pilosebaceous unit. There is about 15% penetration into the pilosebaceous unit with a considerable reservoir within the epidermis and minimal distribution beyond the application site.
The line-up of new topicals for acne is exciting, with most of these new drugs targeting sebum reduction, according to Dr. Kircik.
“That is sort of where the science is going - rather than killing the p. acnes…,” he says.
Acetyl coenzyme A carboxylase inhibitor, which is a prodrug of TOFA (5 tetradecyloxy-2-furoic acid) (DRM01, Dermira) inhibits synthesis of sebum lipids in sebocyte cultures and reduces sebaceous gland size in the hamster ear model.
In an early phase study, lesion count reduction for DRM01 was 64% lesion versus 46% for the vehicle. The active had a 48% noninflammatory lesion count reduction versus 25% for vehicle, as well as about a two grade improvement, or 24.5% , active versus 7.3% vehicle.
“This is another product that will hopefully be on the market soon. We’re doing the phase 2 studies now,” Dr. Kircik says.
MTC896 (Mimetica Pty Limited), a melanocortin-5 receptor antagonist, is in early phases of research.
“Instead of looking at lesion count, they’re looking at sebum reduction. That’s fine and dandy but, if we’re going to use it to treat acne, eventually we’re going to need lesion count reduction,” Dr. Kircik says.
Yet another contender: nitric oxide in a nanotechnology vehicle (Novan).
“[It has multiple modes of antimicrobial function without antibacterial resistance so far, it is anti-inflammatory. It’s an interesting product. It does have good lesion count reduction. We are about to start phase 3 studies on it. In a phase 2 study, it does decrease sebum,” Dr. Kircik says.
The shift to inhibit sebum in acne treatment, versus killing p. acnes, is a new discovery and a novel pathway, according to Dr. Kircik.
It’s exciting, but we’re not there yet, he says.
Disclosure: Dr. Kircik has served as an advisor, investigator, consultant and speaker for Allergan, Bayer, Galderma, Promius Pharma, Quinnova, Stiefel/GSK, Valeant and Warner Chilcott, Dermira, Novan.