Tradipitant was shown to improve the intensity of the worst itch patients experienced, as well as atopic dermatitis disease severity.
Atopic dermatitis is a very common skin disorder affecting millions of people worldwide. Treatment in atopic dermatitis often begins with non-pharmacologic measures and progresses to the use of topical corticosteroids, topical calcineurin inhibitors and topical PDE4 inhibitors.
Systemic treatments approved by the U.S. Food and Drug Administration (the FDA) include corticosteroids and recently dupilumab, an IL-4 receptor alpha inhibitor, for moderate and severe disease.
The American Academy of Dermatology (AAD) recommends that systemic corticosteroid treatment should be generally avoided because of the potential of short-term and long-term adverse reactions to these agents.
At this time, there are very few safe systemic treatments for atopic dermatitis. Vanda designed this Phase II study to assess whether the systemic administration of the oral neurokinin-1 receptor (NK-1R) antagonist, tradipitant could improve chronic pruritus and the severity of atopic dermatitis.
Tradipitant demonstrated significant and clinically meaningful improvement in a number of measures of itch. Specifically, significant improvements were observed in the measurement of Worst Itch Visual Analog Scale (VAS) (p=0.019). Tradipitant also showed significant effects in a responder analysis for Worst Itch in patients who achieved improvements of greater than or equal to 40 points improvement from baseline in Worst Itch VAS scores (p=0.037) or greater than or equal to 30 points (p=0.049).
On the pre-specified primary endpoint of Average Itch VAS, tradipitant showed improvement over placebo, but this improvement was not significant due to high placebo effect and the lack of sensitivity of this measure.
Consistent with the observed improvements in Worst Itch, which is associated with scratching behavior, tradipitant also demonstrated disease modifying properties by showing significant improvement in the Total SCORAD scale (p=0.008) and Objective SCORAD scale (p=0.005).
Specifically, tradipitant showed significant improvements in several clinical features of severity of atopic dermatitis, including excoriation, erythema, oozing and dryness.
These clinically meaningful effects were also accompanied by significant improvements in the Clinical Global Impression scale – Change (CGI-C) (p=0.007), the Patient Global Impression scale (PGI-C) Itch (p=0.024) the PGI-C AD (p=0.007). Similarly, tradipitant also showed direct patient reported benefits as measured by the Patient Benefit Index scale (PBI) (p=0.037).
"We are extremely pleased with the outcome of this study where clinically meaningful differences were observed not just in the symptom of the worst itch in patients suffering from atopic dermatitis but also in measures of disease severity. We believe that tradipitant's ability to significantly help the underlying pathophysiology of atopic dermatitis represents a potentially significant medical advance in treating these patients," said Mihael H. Polymeropoulos, MD, Vanda's President and CEO.
"It's exciting to see results here with significant and highly meaningful improvements in both worst itch as well as a recovery in the lesions for patients in the study," said Gil Yosipovitch, MD, Professor of Dermatology, Miller School of Medicine, and Director of the Miami Itch Center at the University of Miami as well as an investigator in this study.
"These results over 8 weeks provide further confirmation that breaking the itch-scratch cycle causing neural sensitization can have a profound benefit for patients and help ameliorate atopic dermatitis itself. Today, there are limited treatment options for the many patients who suffer from atopic dermatitis, making this study outcome a very promising step towards becoming a major advancement in the armamentarium for physicians."
In this Phase II study, 168 patients were randomized 1:1 to receive either tradipitant 85 mg BID or placebo for a period of 8 weeks. Entry criteria included patients suffering from moderate or severe itching with mild to severe atopic dermatitis excluding only the most severe patients with an upper limit of 80 on total SCORAD (average baseline total SCORAD=47).Tradipitant was found to be safe and well tolerated with minimal adverse events recorded.
Vanda believes that if these results are further confirmed in future studies, tradipitant has the potential to become a first line pharmacological option in the treatment of patients with atopic dermatitis in need of systemic treatment. The detailed results of this study are expected to be presented in upcoming meetings and prepared for peer reviewed publications.
In addition, Vanda expects to meet with the FDA in the near future to further define and confirm the clinical development path towards registration of tradipitant in the treatment of patients with atopic dermatitis.