WASHINGTON, Feb. 25, 2020 /PRNewswire/ -- Vanda
Pharmaceuticals Inc. (Vanda) (Nasdaq:VNDA) today announced results
from a Phase III clinical trial (EPIONE) of tradipitant for the
treatment of pruritus in atopic dermatitis (AD) in adults. The
EPIONE study did not meet its primary endpoint in reduction of
pruritus across the overall study population. However, the
antipruritic effect of tradipitant was robust in the mild AD study
population. Mild AD represents over 60% of the total AD population
in the U.S.1, 2 The EPIONE study continued to
demonstrate that tradipitant is safe and well-tolerated.
"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
Mihael H. Polymeropoulos, M.D.,
Chief Executive Officer of Vanda. "Due to their potent
immuno-suppressive effects, current systemic therapies for AD are
typically only used in moderate to severe AD. The safe profile of
tradipitant, coupled with a significant and immediate onset of itch
reduction by the first full day of treatment, may provide a
much-needed therapy for the majority of AD patients that experience
mild AD lesion severity but still suffer from significant
pruritus."
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 American Academy of Dermatology (AAD)
atopic dermatitis guidelines lists pruritus as an essential feature
of atopic dermatitis.5 The significant pruritus
associated with mild AD and the worsening of lesions through
scratching, along with the sleep disruption, continue to represent
a significant unmet medical need.
"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. Sonja Stander, professor of Dermatology and
Neurodermatology at the Department of Dermatology, and head of the
Interdisciplinary Center for Chronic Pruritus (KCP) of the
University Hospital Münster, Germany.
Dr. Stander added, "we also see patients with moderate-to-severe
disease where immunomodulatory therapies may have a profound effect
on healing lesions in the short term but they still suffer from
significant itch. The NK-1 antagonist mechanism may work well for
this population where only the severe itch is left and their
disease is mild or almost clear after steroids, an interleukin
inhibitor, or another immunomodulatory therapy has been
used."
The results of the EPIONE study suggest that tradipitant can
produce a large and rapid antipruritic effect in mild AD.
Currently, American Academy of Dermatology (AAD) treatment
guidelines indicate and recommend immunomodulatory medications only
after topical regimens and phototherapy are found to not adequately
control the disease.6 A well-tolerated, systemic
antipruritic agent with rapid onset of action, like tradipitant,
could add significant value to patients and take a primary place in
the treatment algorithm of atopic dermatitis.
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 Pharmaceuticals Inc.
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 Vanda
Pharmaceuticals Inc., please visit www.vandapharma.com.
Corporate Contact:
AJ Jones II
Chief Corporate Affairs and Communications Officer
Vanda Pharmaceuticals Inc.
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 December 31, 2018 and quarterly report on Form
10-Q for the fiscal quarter ended September
30, 2019, which are on file with the SEC and available on
the SEC's website at www.sec.gov. Additional factors may be set
forth in those sections of Vanda's annual report on Form 10-K for
the fiscal year ended December 31,
2019, to be filed with the SEC in the first quarter of 2020.
In addition to the risks described above and in Vanda's annual
report on Form 10-K and quarterly reports on Form 10-Q, other
unknown or unpredictable factors also could affect Vanda's results.
There can be no assurance that the actual results or developments
anticipated by Vanda will be realized or, even if substantially
realized, that they will have the expected consequences to, or
effects on, Vanda. Therefore, no assurance can be given that the
outcomes stated in such forward-looking statements and estimates
will be achieved. All written and verbal forward-looking statements
attributable to Vanda or any person acting on its behalf are
expressly qualified in their entirety by the cautionary statements
contained or referred to herein. Vanda cautions investors not to
rely too heavily on the forward-looking statements Vanda makes or
that are made on its behalf. The information in this release is
provided only as of the date of this release, and Vanda undertakes
no obligation, and specifically declines any obligation, to update
or revise publicly any forward-looking statements, whether as a
result of new information, future events or otherwise.
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.
View original content to download
multimedia:http://www.prnewswire.com/news-releases/vanda-reports-results-from-the-epione-study-of-tradipitant-in-the-treatment-of-pruritus-in-atopic-dermatitis-301011169.html
SOURCE Vanda Pharmaceuticals Inc.