WASHINGTON, Aug. 31, 2020 /PRNewswire/ -- Vanda
Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today provided an
update on its development program for tradipitant.
- Enrollment in Vanda's Phase III clinical study
(VP-VLY-686-3303) in gastroparesis is expected to be completed in
the first half of 2021
- The article "Efficacy and Safety of Tradipitant in Patients
with Diabetic and Idiopathic Gastroparesis in a Randomized,
Placebo-Controlled Trial" was accepted for publication in
Gastroenterology1
- A new gastroparesis therapy could present a significant
commercial opportunity, with an estimated 6 million people in the
U.S. suffering from gastroparesis
- Interim analysis from ODYSSEY study shows tradipitant may
accelerate clinical improvement in patients with COVID-19
pneumonia2
- Vanda is pursuing multiple short-term and long-term indications
for tradipitant, including treatment of gastroparesis, COVID-19
pneumonia, motion sickness, and atopic dermatitis
Clinical progress of tradipitant in gastroparesis
Tradipitant is advancing in a Phase III study for the treatment
of both diabetic and idiopathic gastroparesis. This study is
30% enrolled at a target of 200 randomized patients, and is
expected to complete enrollment in the first half of 2021.
The previous Phase II study showed significant improvement in
nausea, the key symptom of gastroparesis, as well as significant
improvement in the number of nausea-free days, in patients treated
with 85 mg of tradipitant twice a day for 4 weeks. The Phase
III study is a 12-week study of similar design to the Phase II
study in both target population and endpoints.
The article "Efficacy and Safety of Tradipitant in Patients with
Diabetic and Idiopathic Gastroparesis in a Randomized,
Placebo-Controlled Trial" was accepted for publication in
Gastroenterology. A preprint is available online here.
The article describes the results of Vanda's Phase II double-blind
trial of 152 adults with gastroparesis at 47 sites in the U.S. from
November 2016 through December
2018. Patients receiving tradipitant had a significant
decrease in nausea score (reduction of 1.2) at week 4 compared with
placebo (reduction of 0.7) (p=.0099), and a significant increase in
of nausea-free days at week 4 (28.8% increase on tradipitant vs
15.0% on placebo; p=.0160). Patients with nausea and vomiting at
baseline (n=101) had an even greater decrease in nausea when given
tradipitant (reduction of 1.4) compared with those given placebo
(reduction of 0.4) (p<.0001), as well as an increase in
nausea-free days at week 4 (32.3% improvement on tradipitant vs
7.6% on placebo; p=.0003). The average nausea score was 1 or less
at week 4 in 32.9% of patients given tradipitant compared with
11.8% of patients given placebo (p=.0013). A greater than 1-point
improvement in the gastroparesis cardinal symptom index score was
observed in 46.6% of patients given tradipitant compared with 23.5%
of patients given placebo (p=.0053).
In July 2020, the U.S. Food and Drug Administration (FDA)
approved the use of tradipitant for up to 6 months with an option
of renewal for an individual patient who requested expanded
access. Since then, other patients who experienced a unique
benefit in tradipitant studies have requested expanded access and
their applications are currently under review by the FDA. Although
this expanded access program is not intended primarily for data
collection, Vanda will collect safety data from this cohort of
expanded access patients and include this data in its New Drug
Application (NDA) for gastroparesis.
Preclinical and safety data for tradipitant
A robust package of preclinical work for tradipitant has been
completed, including a 2-year carcinogenicity study, depicted in
Figure 1. Figure 1 also includes a summary of the human
studies through Phase II.
The results from these animal and human studies demonstrate
tradipitant's extensive animal and human testing, and
well-established safety profile. No significant safety signals were
observed in these studies that would be both predictive of clinical
safety and would preclude all further clinical development.
In the human studies, tradipitant was well tolerated in individuals
who received daily doses of tradipitant ranging from less than 50
mg/day to over 170 mg/day.
Vanda believes this entire preclinical package is adequate to
support NDA filings for the short-term indications being
pursued. The FDA has communicated, however, that for treating
patients beyond 12 weeks, it is requiring Vanda to conduct what it
considers to be a standard 9-month non-rodent chronic toxicity
study, which currently limits Vanda's ability to collect safety
data in humans for more than 12 weeks.
The FDA-required study design necessitates the sacrifice of
dozens of animals and Vanda has disputed the necessity of a 9-month
non-rodent chronic toxicity study. Vanda has taken a public
position that unnecessary lethal animal studies should not be
conducted, especially in dogs, as such studies are not
scientifically justified and would not be consistent with Vanda's
scientific and ethical principles, which are shared by many
Americans. Vanda is working with the FDA to resolve this
disagreement.
Despite the disagreement with the FDA, the preclinical package
has allowed Vanda to continue to conduct all the efficacy studies
necessary for NDA filing. The lack of long-term (>12 weeks
in humans) safety data would likely impact the FDA's willingness to
approve tradipitant for a chronic indication. However,
because long-term safety data is not normally a requirement for
short-term indications, and with a preclinical profile that has not
precluded clinical development, Vanda believes the package is
complete for any NDA filing to treat patients for 12 weeks or
less. In gastroparesis, for example, the FDA has communicated
to Vanda that it is considering an indication for the short-term
relief of nausea in gastroparesis. While this short-term
indication is not preferred, Vanda would consider accepting this
limited indication while continuing to pursue a chronic
indication. The chronic treatment of itch in atopic
dermatitis would be expected to have a similar issue in review as
gastroparesis.
The indications of motion sickness and the acute respiratory
distress (pneumonia) associated with COVID-19 are both short-term
indications covering either short-term travel, in the case of
motion sickness, or a week to several weeks course of treatment in
the case of COVID-19 pneumonia. At this time, the COVID-19
pneumonia program is recruiting patients in the Phase III ODYSSEY
study. Preparations for the motion sickness study have
resumed and the study will commence when local restrictions related
to the global COVID-19 pandemic are lifted. Recruiting in the
atopic dermatitis study remains on hold.
Potential market opportunity for gastroparesis
Gastroparesis is a severe, significantly underdiagnosed disease
with increased morbidity and mortality, representing a significant
unmet medical need. The only FDA approved treatment currently
available is metoclopramide, which carries a label restriction of
up to 3 months treatment because of increased risk of
Parkinson's-like symptoms that can be permanent. Off label
treatments include erythromycin, botulinum toxin injections and
gastric stimulators, none of which provide a significant
benefit. Anti-nausea agents, including ondansetron, are also
used as needed, although with incomplete relief.
As a result of this lack of effective therapeutic options,
patients with gastroparesis experience a significant adverse impact
on their social and occupational functioning in addition to
physical symptoms. Given the magnitude of improvements seen
in the Phase II study, tradipitant has the potential to become the
first line option for the treatment of gastroparesis. As a
result of underdiagnosis, it is difficult to estimate with any
precision the number of patients that could be treated with
tradipitant. IQVIA reports more than 300,000 monthly
metoclopramide prescriptions, the equivalent of 300,000 patients
treated with this drug, which is primarily used in the treatment of
gastroparesis. However, the concentrated base of
gastroenterology specialists and the development of new and easy to
use diagnostics, such as a recently approved breath test that can
be performed at home, along with Vanda's significant experience
with patient-based marketing and direct-to-consumer awareness
campaigns, could represent a large commercial opportunity for
Vanda.
Potential timeline and estimated milestones for
tradipitant in gastroparesis
- Q3 2020, Expanded Access individual patient program
- First Half 2021, Enrollment completion of the Phase III
study
- Second Half 2021, NDA submission for tradipitant in
gastroparesis
- Second Half 2022, Commercial launch of tradipitant for the
treatment of gastroparesis, if approved
About Tradipitant
Tradipitant is an NK-1R antagonist licensed by Vanda from Eli
Lilly and Company. Tradipitant is currently in clinical
development for gastroparesis, COVID-19 pneumonia, motion sickness
and atopic dermatitis. The FDA has imposed a partial clinical
hold on tradipitant clinical protocols of longer than 12 weeks
duration.
References
1 Carlin, J. L., Lieberman, V. R., Dahal, A.,
Keefe, M. S., Xiao, C., Birznieks, G., Abell, T. L., Lembo, A.,
Parkman, H., & Polymeropoulos, M. H. (2020). Efficacy and
safety of tradipitant in patients with diabetic and idiopathic
gastroparesis in a randomized, placebo-controlled trial.
Gastroenterology. Advance online publication.
https://doi.org/10.1053/j.gastro.2020.07.029
2 Refer to Company press release titled "Vanda
Pharmaceuticals' Interim Analysis from ODYSSEY Study Shows
Tradipitant may Accelerate Clinical Improvement in Patients with
COVID-19 Pneumonia" issued on August 18,
2020.
https://vandapharmaceuticalsinc.gcs-web.com/node/14256/pdf
About Vanda Pharmaceuticals Inc.
Vanda is a leading 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 and follow us on Twitter @vandapharma.
CAUTIONARY NOTE REGARDING FORWARD LOOKING STATEMENTS
Various statements in this press release, including, but not
limited to statements regarding the completion of Vanda's Phase III
study of tradipitant for the treatment of gastroparesis, the
potential commercial opportunity for tradipitant, the ability of
tradipitant to be a first line treatment option for patients with
gastroparesis, the adequacy of Vanda's safety data and Vanda's
pursuit of both long-term and short-term indications for
gastroparesis, 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, Vanda's ability
to complete enrollment for its Phase III study of tradipitant for
the treatment of gastroparesis, Vanda's ability to complete the
clinical development of, submit NDAs for and obtain regulatory
approval of tradipitant in the treatment of gastroparesis, motion
sickness and atopic dermatitis, Vanda's ability to resolve its
disagreement with the FDA regarding the conduct of a 9-month
non-rodent chronic toxicity study, and the FDA's assessment of the
adequacy of Vanda's safety and efficacy data. 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.
Forward-looking statements in this press release should be
evaluated together with the various risks and uncertainties that
affect Vanda's business and market, particularly those identified
in the "Cautionary Note Regarding Forward-Looking Statements",
"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, 2019, as updated by Vanda's
subsequent Quarterly Reports on Form 10-Q, Current Reports on Form
8-K and other filings with the U.S. Securities and Exchange
Commission, which are available at www.sec.gov.
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 press release is
provided only as of the date of this press 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,
except as required by law.
Corporate Contact:
AJ Jones II
Chief Corporate Affairs and Communications Officer
Vanda Pharmaceuticals Inc.
202-734-3400
pr@vandapharma.com
Elizabeth Van Every
Head of Corporate Affairs
Vanda Pharmaceuticals Inc.
202-734-3400
pr@vandapharma.com
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SOURCE Vanda Pharmaceuticals Inc.