Novel PPARγ modulator reduces acne manifestations

The novel PPARγ modulator NAC-GED 5% was associated with improved acne manifestations in patients with moderate-to-severe acne in a phase 2b study. With an accompanying favourable safety profile, this result warrants the evaluation of NAC-GED 5% in a phase 3 trial.

N-acetyl-GED-0507-34-levo (NAC-GED) is a small molecule developed for the topical treatment of acne. It is formulated as a hydrophilic, non-alcoholic gel. The phase 2b GEDACNE study (EudraCT 2018-003307-19) randomised 450 patients with moderate-to-severe facial acne vulgaris 1:1:1 to treatment with NAC-GED 5% gel, NAC-GED 2% gel, or a placebo. The primary endpoints were the percentage change from baseline in total lesion count and success on the Investigator’s Global Assessment (IGA) scale for acne, defined as a 0 or 1 score (i.e. clear or almost clear skin) or a reduction of at least 2 points. Prof. Mauro Picardo (International Medical University, Italy) presented the primary findings [1,2].

After 12 weeks of treatment, the percentage change from baseline in total lesion count was -57.1% in the NAC-GED 5% arm, -44.7% in the NAC-GED 2% arm, and -33.7% in the placebo arm. Both experimental arms significantly outperformed the placebo arm and the higher dose regimen significantly outperformed the lower dose regimen (P<0.001 for all). The IGA success rates were 45%, 33%, and 24%, respectively, and the differences between the NAC-GED 5% arm and the other 2 arms were significant (P<0.001 for all). Furthermore, significant changes were observed for both inflammatory lesions and non-inflammatory lesions (see Figure). The investigational agent was well tolerated and neither gender nor age influenced responsiveness.

Figure: Changes in inflammatory and non-inflammatory lesion count after 12 weeks of treatment [1]

LC, lesion count; NAC-GED, N-acetyl-GED-0507-34-levo.

“The PPARγ modulator NAC-GED 5% gel achieved both primary endpoints in a population of patients with moderate-to-severe facial acne vulgaris and will therefore be studied in a phase 3 trial,” concluded Prof. Picardo.

1. Picardo M, et al. Successful modulation of the PPARγ-receptor in the treatment of acne vulgaris: results of an international phase 2b study with NAC-GED-0507 gel. The GEDACNE study. Session Acne, Hidradenitis Suppurativa, Rosacea 1, WCD 2023, 3–8 July, Singapore, Singapore.
2. Picardo M, et al. Br J Dermatol. 2022;187(4):507–514.