WASHINGTON, Dec. 3, 2018 /PRNewswire/ -- Vanda
Pharmaceuticals Inc. (Vanda) (Nasdaq:VNDA) today announced that
tradipitant met the primary endpoint in VLY686-2301, a Phase II
clinical study in patients with idiopathic and diabetic
gastroparesis. The study also showed that tradipitant was
well tolerated with comparable rates of adverse events between the
tradipitant and placebo groups.
"The results of the VLY686-2301 study pave the way for further
development of tradipitant as potentially the first new drug for
gastroparesis in almost 40 years. The highly clinically
meaningful and significant improvements observed in the primary
endpoint of nausea, the significant increase in nausea free days,
and the reported overall symptom improvement, suggest a potential
breakthrough discovery in the treatment of the millions of people
estimated to have gastroparesis" said Mihael H. Polymeropoulos MD, Vanda's President
and Chief Executive Officer.
VLY-686-2301 was a Phase II clinical trial that studied the
effects of tradipitant (85 mg twice a day) versus placebo in 141
patients in an Intent To Treat (ITT) population with gastroparesis
over a period of 4 weeks. Several symptom severity scales were used
to assess gastroparesis symptoms, including the Gastroparesis
Symptom Index (GCSI), Patients Assessment of Upper Gastrointestinal
Disorders–Symptoms (PAGI-SYM), and Patient Global Impression of
Change (PGI-C) as well as a Clinician Global Impression of Severity
(CGI-S).
Tradipitant met the primary endpoint of the study of change in
nausea score as measured by patient daily diaries (change of -1.2
for tradipitant versus -0.7 for placebo, p=0.0099) and also met the
related endpoint of improvement in the number of nausea free days
(an addition of 28.8% of days for tradipitant versus 15.0% for
placebo, p=0.0160). Tradipitant also showed significant improvement
in most of the secondary endpoints studied, including the several
key scales reflecting overall gastroparesis symptoms; GCSI
(p=0.0223); PAGI-SYM (p=0.0497); CGI-S (p=0.0207); PGI-C
(p=0.0429). See Table 1.
In a subgroup analysis of patients that experienced both nausea
and vomiting at baseline (n=101), tradipitant showed highly
significant effects on the primary endpoint of change in nausea
score (change of -1.4 for tradipitant versus -0.4 for placebo,
p=0.00002) as well as the number of nausea free days (an addition
of 32.3% for tradipitant versus 7.6% for placebo,
p=0.0003).
Importantly, improvements were also seen in most of the core
gastroparesis symptoms including nausea, vomiting, bloating, and
fullness after meals consistent with an overall improvement and no
associated worsening of any of the core symptoms. Most effects were
apparent by the second week of treatment although improvements
continued through the fourth and last week of treatment in the
tradipitant group. Adverse events were similar in the tradipitant
and placebo arms which confirms prior studies' findings that
tradipitant is well tolerated.
Vanda believes that if these robust efficacy results with a
well-tolerated chronic treatment safety profile are further
confirmed in future studies, tradipitant has the potential to
become a first line pharmacological option in the treatment of
patients with gastroparesis. The detailed results of this study are
expected to be presented in upcoming meetings and peer reviewed
publications.
In addition, Vanda expects to meet with regulatory authorities
in the near future to further define and confirm the path towards
registration of tradipitant in the treatment of patients with
gastroparesis.
Table 1. Study VLY-686-2301 Results Summary*
ITT Population
(n=141)
|
|
Tradipitant
n=73
|
Placebo
n=68
|
p-value
|
Primary End
Point
|
|
|
|
|
|
|
|
DD-Nausea
|
-1.25
|
-0.73
|
0.0099
|
|
|
|
|
Secondary End
Points
|
|
|
|
|
|
|
|
DD-% Nausea Free
Days
|
28.8
|
15.0
|
0.0160
|
|
|
|
|
GCSI
|
-0.93
|
-0.58
|
0.0223
|
|
|
|
|
PAGI-SYM
|
-0.93
|
-0.65
|
0.0497
|
|
|
|
|
CGI-S
|
-1.13
|
-0.74
|
0.0207
|
|
|
|
|
PGI-C
|
2.66
|
3.06
|
0.0429
|
|
|
|
|
|
|
|
|
Vomiting
Population (n=101)
|
|
Tradipitant
n=58
|
Placebo
n=43
|
p-value
|
Primary End
Point:
|
|
|
|
|
|
|
|
DD-Nausea
|
-1.43
|
-0.42
|
<0.0001
|
|
|
|
|
Secondary End
Points:
|
|
|
|
|
|
|
|
DD-% Nausea Free
Days
|
32.3
|
7.6
|
0.0003
|
|
|
|
|
GCSI
|
-1.10
|
-0.60
|
0.0078
|
|
|
|
|
PAGI-SYM
|
-1.06
|
-0.69
|
0.0294
|
|
|
|
|
CGI-S
|
-1.24
|
-0.79
|
0.0229
|
|
|
|
|
PGI-C
|
2.52
|
3.24
|
0.0018
|
|
|
|
|
|
|
|
|
*For DD-Nausea, DD-% Nausea Free Days, GCSI, PAGI-SYM and CGI-S,
the values shown are changes from baseline.
Conference Call
The Vanda management team will host a conference call and live
webcast today, Monday, December 3,
2018, 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 47969899. A
replay of the call will be available on Monday, December 3, 2018, beginning at
11:00 AM ET and will be accessible
until Monday, December 10, 2018, 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 47969899.
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 Gastroparesis
Gastroparesis is a serious medical condition characterized by
delayed gastric emptying associated with the symptoms of nausea,
vomiting, bloating, fullness after meals and abdominal pain, along
with significant impairment of social and occupational
functioning. The estimated prevalence of gastroparesis in the
U.S. is over 5 million patients many of whom remain
undiagnosed.2 Gastroparesis affects mostly women
and it can be of diabetic, idiopathic or other etiology. The
only U.S. Food and Drug Administration approved treatment for
gastroparesis is metoclopramide, approved in 1979, which due to its
potential of severe side effects carries a black box warning and
limitations of use of no more than 3 months. Patients are
faced with limited therapeutic options and clinical guidelines
recommend, in addition to metoclopramide, the off label use of
different drugs including erythromycin, domperidone (not approved
in the U.S.), botulinum toxin injections, gastric stimulators and a
variety of surgical procedures in an effort to relieve even
temporarily some of the symptoms of the disease3.
Gastroparesis treatment represents a significant unmet medical need
as underscored by the testimonies of interested parties and
advocacy organizations including the International Foundation for
Gastrointestinal Disorders (IFFGD) and Gastroparesis Patient
Association for Cures and Treatments, Inc. (G-Pact).
The precise underlying mechanisms leading to gastroparesis are
currently poorly understood and are believed to be diverse in
nature. The consensus suggests that gastroparesis arises from
a dysregulation of the neuromuscular control of gastric movements
that result in the timely emptying of stomach contents. The
two key stimulatory neurotransmitters of the digestive system are
acetylcholine and the neuropeptide substance P. Substance P
acts by binding the neurokinin 1 receptor (NK-1R) at the gastric
neuromuscular junction and it is believed that there is a
functional interplay between the acetylcholine and NK-1R
systems. Moreover gastroparesis symptoms are also associated
with aberrant physiology of the vagus nerve which constitutes the
major connection between the stomach and the central nervous
system.1 Vanda believes that blockade of the
NK-1Rs may have a dual and potentially therapeutic effect in
gastroparesis by affecting gastric motility through a local action
as well as affecting nausea and vomiting via a direct effect in the
brain regions responsible for nausea and vomiting.
About Tradipitant
Tradipitant is an NK-1R antagonist licensed by Vanda from Eli
Lilly and Company in April 2012.
Tradipitant is currently in clinical development for gastroparesis
as well as in Phase III for atopic dermatitis. 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.
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
DD-Nausea: Daily Diary Nausea score (0-5)
DD-% Nausea Free Days: Daily Diary Nausea Free Days percent
(0-100)
ITT: Intent To Treat
GCSI: Gastroparesis Cardinal Symptom Index
PAGI-SYM: Patient Assessment of Gastrointestinal Disorders –
Symptoms
CGI-S: Clinician Global Impression of Severity
PGI-C: Patient Global Impression of Change
References
1. 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.
2. Rey E., Choung RS, Schleck CD, Zinsmeister
AR, Talley NJ, Locke GR 3rd. Prevalence of hidden
gastroparesis in the community: the gastroparesis "iceberg." J
Neurogastroenterol Motil. Vol. 18 No. 1 (2012).
3. Camilleri, M., Chedid, V., Ford, A.C., Haruma, K.,
Horowitz, M., Jones, K.L., Low, P.A., Park, S., Parkman, H.P. and
Stanghellini V. Gastroparesis. Nature Reviews Disease
Primers. 4:14 (2018).
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 gastroparesis and 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; tradipitant's
potential to become a first line pharmacological option in the
treatment of patients with gastroparesis; 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, 2017 and quarterly
report on Form 10-Q for the quarter ended September 30, 2018, which are on file with the
Securities and Exchange Commission (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.