New topical agents on the horizon for eczema treatment
Two novel investigational topical agents show potential in improving symptoms of atopic dermatitis, according to early phase trials presented at the Inflammatory Skin Disease Summit (ISDS) in Vienna, Austria.
In the phase IIb double-blind ADVANTAGE trial, 326 adults with mild-to-moderate atopic dermatitis were randomized 1:1:1 to receive topical cream of a bioactive lipid immunomodulator DS107 5%, 1%, or vehicle cream twice daily for 8 weeks. The participants were assessed at week 10 during follow-up visits. [ISDS 2018, abstract 88]
Disease severity was improved after 8 weeks of treatment, with more patients in both the high-dose and low-dose DS107 groups achieving treatment success than the vehicle group (30.1 percent and 23.5 percent vs 18.8 percent), as defined by a ≥2-point improvement from baseline and scoring clear or almost clear on the Investigator’s Global Assessment (IGA).
During follow-up assessment at week 10, the high-dose DS107 group continued to demonstrate significantly better IGA response than the vehicle group (32 percent vs 16 percent; p=0.029), even though the treatment has been stopped for 2 weeks.
More patients in the high-dose group also achieved ≥75 percent improvement on the Eczema Area and Severity Index (EASI-75) compared with the vehicle group (41 percent vs 30 percent) at week 8. Similarly, follow-up at 10 weeks revealed significantly more patients achieving EASI-75 in the high-dose DS107 group vs the vehicle group (48.2 percent vs 30.9 percent; p=0.019), with the treatment effect showing no signs of plateauing.
“Topical DS107 was safe and well tolerated,” said the researchers, who observed no significant differences in treatment-emergent adverse events (TEAEs) between the treatment groups and the vehicle group.
“With significant clinical improvements in patients with mild‐to‐moderate AD, [topical DS107 thus] offers a new safe and effective treatment option [for these patients],” they concluded, suggesting that the findings may pave way for a phase III trial.
Another double-blind trial investigating the efficacy of topical nitric oxide-releasing cream SB414 showed similarly promising results in improving disease activity and itch in atopic dermatitis. Nitric oxide has been shown to suppress inflammation, which is associated with itchiness in skin conditions.
The phase Ib trial randomized 48 adults with mild-to-moderate atopic dermatitis to receive either topical cream of SB414 2% (n=17), 6% (n=17), or vehicle (n=14) twice daily for 2 weeks. [ISDS 2018, abstract 30]
After 2 weeks, more patients in the high-dose SB414 group had ≥50 percent improvement on EASI (EASI-50) compared with the vehicle group (24 percent vs 21 percent). EASI-50 was 18 percent in the low-dose SB414 group.
Itch symptom also reduced with both high- and low-doses of SB414 at week 2 compared with vehicle cream (59 percent and 41 percent vs 29 percent), as measured on the Itch Numeric Rating Scale.
No TEAEs were reported in the low-dose SB414 group, while application site reactions were observed in two patients each in the high-dose SB414 and the vehicle groups, of which three led to discontinuation of study. No deaths or serious AEs were reported during the study.
“Both SB414 2% and 6% were well tolerated, but the lower dose had a more favourable local tolerability profile,” the researchers pointed out.