The investigational sebum-inhibiting topical DRM01 had positive results in a phase 2b study, which paves the way for phase 3 trials planned for 2017.
DRM01 (Dermira) had positive results in a phase 2a safety and efficacy trial and, more recently, in a phase 2b study looking at dosing of the topical for patients with facial acne vulgaris.
âWhatâs interesting about this drug, in particular, is that this topical treatment for acne works by a unique mechanism of action in that itâs a topical therapy that reduces production of sebum. Excess sebum is one of the elements in the pathogenesis of acne. And this is something that we havenât been able to control with topical treatments â only with oral treatments for acne,â says phase 2b trial investigator Linda Stein Gold, M.D., director of dermatology clinical research and head of dermatology at Henry Ford Hospital, Detroit, Mich.
DRM01 is designed to inhibit acetyl coenzyme-A carboxylase, an enzyme involved in sebum synthesis, according to Dr. Stein Gold.
Dr. BauerDermiraâs cofounder and Chief Medical Officer Eugene A. Bauer, M.D., says DRM01 is a novel, small molecule designed to inhibit sebum production following topical application. Results of the phase 2b clinical show significant improvements in all primary endpoints compared to vehicle at the highest dose of 7.5%, twice daily. Primary endpoints were absolute changes from baseline in inflammatory and non-inflammatory lesion counts and the proportion of patients achieving at least a two-point improvement from baseline on the five-point Investigatorâs Global Assessment (IGA) scale. DRM01 demonstrated significant improvement in most primary endpoints at the two lower doses.
Phase 2b was randomized, multi-center, double-blind, parallel-group, vehicle-controlled study looking at 420 adults with moderate-to-severe facial acne vulgaris at 34 sites in the United States and Canada.
Subjects had a minimum of 20 inflammatory lesions and 20 non-inflammatory lesions and an IGA score of three or greater. Patients apply DRM01 at concentrations of 4.0% once daily, 7.5% once daily, 7.5% twice daily or vehicle once or twice daily for 12 weeks.
They found that in the highest dose active group inflammatory lesions decreased by an average of 15.0 compared to 10.7 in patients in the once and twice daily vehicle group, which equals an average percentage reduction of 55.6% compared to 40.0% in vehicle. The number of non-inflammatory lesions in the highest active group decreased an average 17.5 lesions compared to 9.3 in patients in the combined vehicle group, or an average percentage reduction of 47.8% compared to 28.7% in vehicle.
Nearly 26% of patients in the highest dose DRM01 group achieved a minimum two-grade improvement in IGA score compared to 9.8% of those in the combined vehicle group.
The topical was well tolerated, with 5.4% of subjects reporting nasopharyngitis and 2.5% getting an upper respiratory tract infection or application site itching during the 12-week study.
NEXT: Plans for phase 3
Dermira plans to start a phase 3 program in the first half of 2017, subject to an end-of-phase 2 meeting with the U.S. Food and Drug Administration (FDA), according to a Dermira press release.
Dr. Stein Gold says that she thinks that, if approved, the topical would be appropriate for most types of acne patients, except with nodular and cystic acne.
âSo, for any patient in which topical therapy would be appropriate, I would think this would be an appropriate treatment,â she says. âYou have to remember, in clinical trials you see monotherapy. [In practice], we combine drugs that work by different mechanisms of action.â
Dermira has much in the works to treat dermatology patients, according to Dr. Bauer.
âDermira has two separate phase 3 programs that are being developed for psoriasis and hyperhidrosis,â he says. âDRM04 is our proprietary topical anticholinergic product in phase 3 development for the treatment of primary axillary hyperhidrosis. We are also developing CIMZIA, with our collaboration partner UCB Pharma S.A., as a potential treatment option for patients with moderate-to-severe chronic plaque psoriasis.â