WASHINGTON, Sept. 13, 2017
/PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (NASDAQ: VNDA)
today announced results from an 8-week randomized Phase II clinical
study of tradipitant as a monotherapy in the treatment of chronic
pruritus in patients with atopic dermatitis. 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.
Study 2102 Results Summary
Continuous
|
ITT
population
|
|
|
|
|
|
|
Tradipitant
|
Placebo
|
Diff
|
p-value
|
A. Itch
Outcomes
|
Average Itch
VAS
|
-41.5
|
-35.8
|
-5.7
|
0.306
|
|
Worst Itch
VAS
|
-44.2
|
-30.6
|
-13.6
|
0.019
|
|
Worst Itch NRS
Night
|
-3.4
|
-2.4
|
-1.1
|
0.029
|
|
Worst Itch NRS
Day
|
-3.3
|
-2.5
|
-0.8
|
0.074
|
|
|
|
|
|
|
B. Disease
Outcomes
|
SCORAD
Total
|
-21.3
|
-13.6
|
-7.7
|
0.008
|
|
Objective
SCORAD
|
-13.3
|
-7.2
|
-6.1
|
0.005
|
|
Subjective
SCORAD
|
-8.1
|
-6.7
|
-1.4
|
0.157
|
|
|
|
|
|
|
C. General
Impression Outcomes
|
CGI-C
|
2.6
|
3.3
|
-0.7
|
0.007
|
|
PGI-C Itch
|
2.6
|
3.2
|
-0.6
|
0.025
|
|
PGI-C AD
|
2.7
|
3.4
|
-0.7
|
0.007
|
|
|
|
|
|
|
D. Quality of Life
Outcomes
|
PBI
|
1.7
|
1.2
|
0.5
|
0.038
|
|
SKINDEX 16
|
-34.8
|
-26.6
|
-8.2
|
0.102
|
|
|
|
|
|
|
Categorical
|
ITT
population
|
|
|
|
|
|
|
Tradipitant
|
Placebo
|
Diff
|
p-value
|
A. Itch
Outcomes
|
Worst Itch VAS
>=40
|
52.6%
|
34.7%
|
17.9%
|
0.037
|
|
worst Itch VAS
>=30
|
56.6%
|
38.9%
|
17.7%
|
0.049
|
|
|
|
|
|
|
B. Disease
Outcomes
|
SCORAD
>=50%
|
44.0%
|
20.8%
|
23.2%
|
0.004
|
|
EASI
>=75%
|
21.1%
|
11.1%
|
10.0%
|
0.067
|
Further data and tables can be found at
http://mma.prnewswire.com/media/555779/VLY_Plots_Final.pdf
Conference Call
The Vanda management team will host a conference call and live
webcast tomorrow, September 14, 2017,
at 8:30 AM ET to discuss these
updates. Investors can call 1-888-771-4371 (domestic) or
1-847-585-4405 (international) and use passcode 45656982. A replay
of the call will be available on Thursday,
September 14, 2017, beginning at 11:00 AM ET and will be accessible until
Thursday, September 21, 2017, at
11:59 PM ET. The replay call-in
number is 1-888-843-7419 for domestic callers and 1-630-652-3042
for international callers. The passcode number is 45656982.
The conference call will be broadcast simultaneously on Vanda's
website. Investors should click on the Investor Relations tab and
are advised to go to the website at least 15 minutes early to
register, download, and install any necessary software or
presentations. The call will also be archived on Vanda's website
for a period of 30 days.
About Atopic Dermatitis and Chronic Pruritus
Atopic dermatitis is a common chronic, relapsing inflammatory
skin disorder characterized by the symptom of intense and
persistent pruritus or itch. Other clinical features include
erythema, excoriation, edema, lichenification, oozing and
xerosis.
About the Neurokinin-1 Receptor and Substance P
The NK-1R is expressed throughout different tissues of the body,
with major activity found in neuronal tissue. SP and NK-1R
interactions in neuronal tissue regulate neurogenic inflammation
locally and the pain perception pathway through the central nervous
system. Other tissues, including endothelial cells and immune
cells, have also exhibited SP and NK-1R activity (2). The
activation of NK-1R by the natural ligand SP is involved in
numerous physiological processes, including the perception of pain,
behavioral stressors, cravings and the processes of nausea and
vomiting (1,2,3). An inappropriate over-expression of SP, either in
nervous tissue or peripherally, could result in pathological
conditions such as substance dependence, anxiety, nausea/vomiting
and pruritus (1,2,3,4). An NK-1R antagonist may possess the ability
to reduce this over-stimulation of the NK-1R, and as a result
address the underlying pathophysiology of the symptoms in these
conditions.
About Tradipitant
Tradipitant is an NK-1R antagonist licensed by Vanda from Eli
Lilly and Company (Lilly) in April
2012. Tradipitant is currently in clinical development for
chronic pruritus in patients with atopic dermatitis. Previous
research at Lilly focused on the potential of tradipitant as a
novel therapeutic in alcohol dependence (1). The patent describing
tradipitant as a new chemical entity is expected to expire in
the United States in June 2029 based on an anticipated Hatch-Waxman
patent term extension and expires worldwide in April 2023 absent any other applicable patent
term adjustments.
About Vanda
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.
Abbreviations
BID
|
Twice
daily
|
CGI-C
|
Clinical Global
Impression of Change
|
EASI
|
Eczema Area and
Severity Index
|
NK-1R
|
Neurokinin-1
Receptor
|
NRS
|
Numerical Rating
Scale
|
PBI
|
Patient Benefit
Index
|
PGI-C AD
|
Patient Global
Impression of Change Atopic Dermatitis specific
|
PGI-C Itch
|
Patient Global
Impression of Change Itch specific
|
SCORAD
|
SCORing Atopic
Dermatitis Index
|
SKINDEX
|
Brief Quality-of-Life
Measure for Patients with Skin Diseases
|
SP
|
Substance
P
|
VAS
|
Visual Analog
Scale
|
References
1. George DT, Gilman J, Hersh J, Thorsell A, Herion D, Geyer C,
Peng X, Keilbasa W, Rawlings R, Brandt JE, Gehlert DR, Tauscher JT, Hunt SP, Hommer D, Heilig M.
Neurokinin 1 receptor antagonism as a possible therapy for
alcoholism. Science. 2008; 319(5869):1536-9.
2. Almeida TA, Rojo J, Nieto PM, Pinto FM, Hernandez M, et al.
Tachykinins and tachykinin receptors: structure and activity
relationships. Current Medicinal Chemistry. 2004;11:2045-2081.
3. Hargreaves R, Ferreira JC, Hughes D, Brands J, Hale J,
Mattson B, Mill S. Development of aprepitant, the first
neurokinin-1 receptor antagonist for the prevention of
chemotherapy-induced nausea and vomiting. Annals of the New York
Academy of Sciences. 2011; 1222:40-48.
4. Staender S, Weisshaar E, Luger A. Neurophysiological and
neurochemical basis of modern pruritus treatment. Experimental
Dermatology. 2007;17:161-69.
FORWARD LOOKING STATEMENTS
Various statements in this release 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 NK-1R inhibition to provide significant
benefit in the treatment of chronic pruritus in patients with
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; and other factors that are
described 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, 2016 and quarterly
report on Form 10-Q for the quarter ended June 30, 2017, which are on file with the SEC and
available on the SEC's website at www.sec.gov. 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.
Corporate Contact:
Jim
Kelly
Executive Vice President and Chief Financial
Officer
Vanda Pharmaceuticals Inc.
(202) 734-3428
jim.kelly@vandapharma.com
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SOURCE Vanda Pharmaceuticals Inc.