NEW YORK (Reuters Health) - An investigational nonsteroidal topical cream (PAC-14028, or Asivatrep) may be a safe, effective treatment for atopic dermatitis, Korean researchers suggest.
The medication reportedly reduces pruritus and inflammation by blocking transient receptor potential vanilloid subfamily, member 1 (TRPV1), a cation channel involved in the perception of pain.
In a randomized, double-blind, placebo-controlled multicenter phase IIb trial, PAC-14028 applied topically as a 0.1%, 0.3% or 1.0% cream significantly improved the signs and symptoms of patients with atopic dermatitis (AD), according to a report online January 8 in the British Journal of Dermatology.
"Asivatrep (PAC-14028) is a novel and potent TRPV1 antagonist with anti-inflammatory, anti-pruritic, and epidermal barrier recovery activities," corresponding author Dr. Miyoung Park, of the AmorePacific Corp. R&D Unit, in Yongin told Reuters Health by email.
The researchers expect the new drug to show advantages over other classes of AD drugs, such as topical calcineurin inhibitors or a PDE4 inhibitor, in terms of efficacy and safety profiles, Dr. Park added.
The 194 patients in the trial (mean ages 26-28) applied the product (or a placebo cream) to AD-affected areas twice daily.
All participants had an Investigator's Global Assessment (IGA) score of 2 or 3 (on a scale of 0-5), indicating mild to moderate AD. The primary outcome was the percentage of patients whose IGA score was 0 or 1 after eight weeks of treatment.
IGA success rates were 14.6% for placebo, 42.6% for PAC-14028 cream 0.1% (P = 0.0025 vs. vehicle), 38.3% for 0.3% cream (P = 0.0087 vs. vehicle) and 57.5% for 1.0% (P < 0.001 vs. vehicle).
By week 8, the proportion of patients achieving treatment success, based on an IGA score with a two-grade improvement from baseline, was significantly higher in 0.1% (21.3%), 0.3% (27.7%) and 1.0% (38.3%) groups than in the placebo group (4.2%).
Use of the 1.0% cream was associated with improvements in patient-reported symptoms of AD, including pruritus and sleep.
Adverse events were mild or moderate, and there were no clinically meaningful differences in the rates of adverse events or adverse drug reactions among the treatment arms.
The report notes that a phase 3 trial is under way to assess the efficacy and safety of PAC-14028 topical cream 1.0% in adolescent and adult patients with mild to moderate AD.
Dr. Lawrence Eichenfield, chief of Pediatric and Adolescent Dermatology and vice chair of the Department of Dermatology, the University of California, San Diego and Rady Children's Hospital, San Diego, told Reuters Health by email that in eczema, "Transient receptor potential channels can be seen on sensory nerves, as well as other non-nerve cells in the skin. TRPV1 appears to be important in inflammation and itch in atopic dermatitis."
Though this was a small study, Dr. Eichenfield said, it "suggests an intriguing new potential therapy for atopic dermatitis. Having a non-steroid topical agent that is well tolerated and improves the rash and itch of eczema could be very helpful to minimizing eczema's impact."
Dr. Whitney A. High, director of dermatopathology/dermatology at the University of Colorado School of Medicine, told Reuters Health by email that the study was well designed but cautioned that AD "is, by and large, a disease chiefly of childhood, and the study examined adult atopic dermatitis . . . The degree to which this study would be similar, had it involved childhood atopic dermatitis, which differs somewhat from adult dermatitis, is unknown."
That the study drug seemed to be well tolerated, with few adverse effects, he said, is important because the backbone of treating atopic dermatitis is often topical corticosteroids, "and this class of medications often has diminished efficacy over time ... and some undesirable side-effects, like skin thinning, skin fragility, striae (stretch marks), and telangiectasias."
If it ultimately is approved and released, Dr. High said, "I could see PAC-14028 being used much like tacrolimus and pimecrolimus (topical calcineurin inhibitors). In fact, the direct antipruritic effect is appealing."
He cautioned, however, that like tacrolimus and pimecrolimus, PAC-14028 will be expensive, so "insurance companies will limit use in terms of both who may get the medication and how much medication they can have at once."
The study was funded by AmorePacific Corp. Dr. Kim is an AmorePacific employee, two of Dr. Kim's seven co-authors have been speakers or consultants for AmorePacific Corp. and other companies, and another author has multiple ties to various pharma companies.
SOURCE: https://bit.ly/2HpLEYE
Br J Dermatol 2019.
Correspondence information about the author PhD Wen-Qing Li
Email the author PhD Wen-Qing Li
Correspondence information about the author PhD Wen-Qing Li
Email the author PhD Wen-Qing Li
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