"Although we are disappointed that EPIONE did not meet its primary endpoint, the profile of efficacy demonstrated in this study potentially addresses a highly unmet need of treating intractable pruritus for a large portion of AD patients," said
EPIONE was a randomized, placebo-controlled Phase III study (n=341) in AD patients with severe pruritus with a range of disease severity presentation from mild (23%) to moderate (64%) and severe (13%) as determined by the Investigator's Global Assessment scale (IGA). Patients were randomized 1:1 to receive either tradipitant or placebo for a treatment period of 8 weeks. Patients were assessed at baseline and post-randomization with a number of symptomatic and disease severity scales at regular intervals.
The EPIONE study examined the hypothesis that tradipitant dosed at 85 mg twice a day offers improvement of the disease symptoms and signs of AD over the evaluation period. At week 8, tradipitant and placebo patients demonstrated significant and meaningful improvement in pruritus as measured by the Worst Itch Numeric Rating Scale (WI-NRS), but while the tradipitant magnitude of improvement was greater than that of placebo, the difference between treatment groups was not statistically significant. A significant interaction was observed between baseline disease severity (IGA 1-4) and treatment (p=0.0004). This suggests that study participants with different baseline disease severity experienced different treatment outcomes. When accounting for baseline disease severity and treatment interaction, a significantly larger improvement in WI-NRS was seen with tradipitant at the pre-specified endpoint of Week 8 in the full trial population (p=0.0217). Similar effects were seen throughout the treatment periods at all post-randomization visits comprising weeks 2, 4, 6 and 8 (Table 1).
Given the observed significant interaction between baseline disease severity and treatment, a subgroup analysis showed that patients with mild disease severity (23% of study patients, IGA 1, 2) experienced the largest improvement over placebo. Specifically, in the mild AD group, tradipitant significantly improved WI-NRS over placebo at every visit (Table 1, Figure 1). The categorical WI-NRS responder analysis (>4 point improvement) showed that 72.5% of tradipitant patients had a clinically meaningful response as compared to 33.3% of placebo patients.
These results suggest a large and significant antipruritic effect of tradipitant in mild AD, and were confirmed with patient daily diary entries. For mild AD patients, a time course of response also showed that the antipruritic effect was seen immediately after the first full day of tradipitant dosing, suggesting a large and immediate therapeutic effect. Similar improvement was observed for nighttime sleep, often disrupted in patients with severe pruritus.
Results from the EPIONE study (Figure 2) and scientific literature suggest that mild and severe AD appear to be distinct endotypes with different sets of causative factors and course.3, 4
"The majority of AD patients across all age groups from children to seniors suffer from a form of atopic dermatitis characterized by mild lesions. Yet these patients might still have severe pruritus and suffer from impacts to quality of life, as well as sleep. With a beneficial safety profile and assuming this significant improvement in itch in the mild-type atopic dermatitis is confirmed in a future study, this therapy would be of interest to all these mild-type AD patients," said Dr.
The results of the EPIONE study suggest that tradipitant can produce a large and rapid antipruritic effect in mild AD. Currently,
The results of the EPIONE study will need to be confirmed in a follow up study. Vanda plans to reassess the ongoing EPIONE2 study of pruritus in AD as it continues to analyze the results and determines next steps.
About
Vanda is a global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on
Corporate Contact:
AJ Jones II
Chief Corporate Affairs and Communications Officer
202-734-3400
pr@vandapharma.com
CAUTIONARY NOTE REGARDING FORWARD LOOKING STATEMENTS
Various statements in this release, including, without limitation, statements regarding the efficacy of traidipitant in the treatment of pruritus in patients with mild atopic dermatitis and the potential commercial opportunity for tradipitant, are "forward-looking statements" under the securities laws. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others: the ability of tradipitant to provide significant benefit in the treatment of pruritus in patients with mild atopic dermatitis; the results of Vanda's clinical development activities for tradipitant; delays in the completion of Vanda's clinical development of tradipitant; a failure of tradipitant to be demonstrably safe and effective; tradipitant's potential to become a first line pharmacological option in the treatment of pruritis in patients with mild atopic dermatitis; and other factors that are set forth in the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's annual report on Form 10-K for the fiscal year ended
Table 1. EPIONE Summary Results
Endpoints1 |
Visit |
Tradipitant |
Placebo |
Diff |
P-value |
WI-NRS |
Week 2 |
-1.68 |
-1.44 |
0.23 |
0.3092 |
ITT (n=341) |
Week 4 |
-2.58 |
-2.20 |
0.39 |
0.1664 |
Tradipitant (n=171) |
Week 6 |
-3.00 |
-2.89 |
0.11 |
0.7105 |
Placebo (n=170) |
Week 8 |
-3.61 |
-3.43 |
0.18 |
0.5667 |
WI-NRS Adjusting for IGA Severity |
Week 2 |
-2.43 |
-1.29 |
1.14 |
0.0069 |
ITT (n=341) |
Week 4 |
-3.34 |
-2.05 |
1.29 |
0.0042 |
Week 6 |
-3.75 |
-2.74 |
1.01 |
0.0284 |
|
Week 8 |
-4.36 |
-3.28 |
1.08 |
0.0217 |
|
WI-NRS |
Week 2 |
-2.59 |
-0.98 |
1.61 |
0.0003 |
IGA 1, 2 (n=79) |
Week 4 |
-3.39 |
-1.48 |
1.92 |
0.0005 |
Tradipitant (n=40) |
Week 6 |
-4.18 |
-2.32 |
1.86 |
0.0024 |
Placebo (n=39) |
Week 8 |
-4.74 |
-3.14 |
1.60 |
0.0152 |
Diary WI-NRS |
Week 2 |
-1.54 |
-0.36 |
1.18 |
0.0002 |
IGA 1, 2 (n=79) |
Week 4 |
-2.78 |
-1.07 |
1.71 |
0.0002 |
Week 6 |
-3.48 |
-1.72 |
1.76 |
0.0011 |
|
Week 8 |
-4.23 |
-2.14 |
2.09 |
0.0010 |
|
Responder Analysis (%)2(n=79) |
|||||
WI-NRS ≥4 Improvement |
Week 8 |
72.5 |
33.3 |
39.2 |
0.0007 |
SCORAD 50% Improvement |
Week 8 |
55.0 |
30.8 |
24.2 |
0.0411 |
IGA 0 or 1 |
Week 8 |
60.0 |
38.5 |
21.5 |
0.0729 |
1. |
P-values are from MMRM analysis. |
2. |
P-values are from Fisher's exact test. |
References:
- Chiesa Fuxench ZC, Block J, Boguniewicz M, et al. Atopic Dermatitis in America Study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. J Invest Dermatol. 2019 Mar; 139(3): 583-590.
- Silverberg JI, Simpson EL. Associations of childhood eczema severity: a US population-based study. Dermatitis. 2014; 25(3): 107–114.
- Czarnowicki T, He H, Krueger, JG,
Guttman-Yassky E . Atopic Dermatitis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol. 2019 Jan; 143(1): 1-11. - Brown SJ, McLean WHI, Eczema Genetics: Current State of Knowledge and Future Goals. J Invest Dermatol. 2009; 129: 543–552.
- Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: Section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014; 70: 338–51.
- Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: Section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014; 71: 327–49.
- Yosipovitch G, Berger T, Fassett MS. Neuroimmune interactions in chronic itch of atopic dermatitis. J Eur Acad Dermatol Venereol. 2020 Feb; 34(2): 239-250.
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