SLOUGH, England, May 5, 2015
/PRNewswire/ -- Indivior PLC (LON: INDV) today announced
top-line results from its phase 3 clinical trial of RBP-7000, an
investigational drug in development for the treatment of
schizophrenia. In this pivotal study, both doses of RBP-7000
tested, 90 mg and 120 mg administered once-monthly, met the primary
endpoint with statistically and clinically significant reductions
in the symptoms of acute schizophrenia over an 8-week treatment
period. Symptom reduction was measured using the change from
baseline to end of treatment in the total Positive and Negative
Syndrome Scale (PANSS) scores. RBP-7000 also met the key secondary
endpoint with statistically significant improvements in the
Clinical Global Impression-Severity of Illness (CGI-S) scale
compared with placebo over the 8-week treatment period using change
from baseline to end of treatment.
"With these positive phase 3 data in hand, we are moving forward
expeditiously to complete the open-label long-term assessment of
the safety and tolerability of RBP-7000," said Christian Heidbreder, Ph.D., Chief Scientific
Officer of Indivior. "We understand there is a great unmet need
among patients living with this chronic disease, and we hope to
bring a new, long-acting treatment option to those individuals and
the physicians who treat them."
Based on the success of the open-label phase of the trial,
Indivior expects to submit a New Drug Application (NDA) to the U.S.
Food and Drug Administration for potential approval in 2017.
During the 8-week, double-blind treatment period, patients
treated once-monthly with either 90 mg or 120 mg of RBP-7000
demonstrated statistically and clinically significant mean
reductions from baseline in PANSS total scores (-9.2 points for
placebo; -15.4 points for RBP-7000, 90 mg, p=0.0004 vs. placebo;
and -16.4 points for RBP-7000, 120 mg, p<0.0001 vs. placebo). In
addition to meeting the pre-specified primary efficacy endpoint of
PANSS total score reduction, the study also met the pre-specified
key secondary endpoint of improvement on the CGI-S scale for each
RBP-7000 group vs. placebo at Week 8 (p=0.0002 vs. placebo for
RBP-7000, 90 mg; and p<0.0001 vs. placebo for RBP-7000, 120 mg).
RBP-7000 was generally well tolerated in the study, and the
observed safety profile of RBP-7000 was similar to that reported
with oral risperidone.
Schizophrenia is a chronic, severe and disabling brain
disorder1 that affects an estimated 26 million people
worldwide.2 Treatment is aimed at reducing or
eliminating the symptoms of the disease and often includes
antipsychotic medications and various psychosocial
treatments.1
About the Study Design
The phase 3, randomized,
multicenter, double-blind, placebo-controlled study was designed to
assess the efficacy, safety and tolerability of RBP-7000 (90 mg and
120 mg) in patients experiencing acute exacerbation of
schizophrenia. The trial included adult male and female patients
between the ages of 18 to 55 years who met the Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition, Text
Revision (DSM-IV-TR®) criteria for schizophrenia and had
a PANSS total score between 80 and 120 at the initial screening
visit, and a score of 4 or greater on at least two of the following
four items of the PANSS positive subscale: hallucinatory behavior,
delusions, conceptual disorganization or suspiciousness.
A total of 354 patients were randomized to receive once-monthly
subcutaneous injections of RBP-7000, 90 mg; RBP-7000, 120 mg; or a
matching placebo injection for 8 weeks. Following randomization,
patients received their first injection of RBP-7000.
The primary efficacy endpoint of the study was the mean change
from baseline at Week 8 in PANSS total score. Statistical analyses
of the effect of study treatment vs. placebo on the primary
efficacy endpoint were conducted using a mixed effects model for
repeated measures taking into account all available observations of
the primary efficacy endpoint at various visits, and including
terms for treatment (RBP-7000 [90 mg], RBP-7000 [120 mg], placebo),
baseline total PANSS score, visit (5, 6, 8, 9) and
treatment-by-visit interaction as fixed effects. The unstructured
covariance type was used to model the variance-covariance matrix.
Dunnett's procedure was used to adjust for the comparison between
two levels of study treatment (RBP-7000 [90 mg and 120 mg]) with a
single placebo.
All participants who completed the double-blind portion of the
study and met some additional inclusionary/exclusionary criteria
were eligible to continue in an open-label phase and receive
RBP-7000 for a total of 13 injections (2 in the double-blind phase
and 11 in the open-label phase). The objective of the extension
phase of the study is to assess the safety and long-term
tolerability of once-monthly RBP-7000.
About RBP-7000
RBP-7000 is a novel sustained-release
product using the Atrigel® delivery system for the
subcutaneous administration of risperidone once every
month.3 RBP-7000 consists of a two-syringe system, whose
contents are mixed immediately prior to administration. One syringe
contains the Atrigel® delivery system, and the other
contains the powder-filled drug substance risperidone. These phase
3 clinical trial results further emphasize the compatibility of our
Atrigel® drug delivery platform with a range of
pharmaceutical compounds for their safe, sustained release over
targeted time period through an easy biodegradable and
biocompatible process.
About Schizophrenia
Schizophrenia is a chronic
disorder characterized by a life-long pattern of acute psychotic
episodes superimposed upon chronically poor psychosocial
adjustment. The symptoms can be grouped into four domains: positive
(e.g., delusions, hallucinations, disorganized speech and
behavior); negative (e.g., social withdrawal, avolition, blunted
affect); cognitive (e.g., impaired sustained attention, executive
function and working memory) and affective (e.g., anxiety and
depression, hostility and aggression, increased risk of suicide)
symptoms. These occur in different combinations and to a different
degree in each patient. Given the extensive heterogeneity of
symptoms among individual patients, schizophrenia can be considered
a clinical syndrome rather than a single disease entity.
Schizophrenia leads to high direct and indirect costs and accounts
for 1.5-3 percent of national healthcare expenditures across
countries.3
About Indivior
Indivior is a global specialty
pharmaceutical company with a 20-year legacy of leadership in
patient advocacy, health policy and evidence-based best practice
models that have revolutionized modern addiction treatment. The
name is the fusion of the words individual and endeavor, and the
tagline "Focus on you" makes the company's commitment clear.
Indivior is dedicated to transforming addiction from a global human
crisis to a recognized and treated chronic disease. Building on its
robust, global opioid dependence portfolio featuring
SUBOXONE® (buprenorphine and naloxone) Sublingual Film
(CIII), SUBOXONE® (buprenorphine and naloxone)
Sublingual Tablet, and SUBUTEX® (buprenorphine)
Sublingual Tablet, Indivior has a strong pipeline of product
candidates designed to both expand on its heritage in this category
and address other chronic diseases of addiction – including opiate
overdose, alcohol use disorders and cocaine intoxication. It also
is pursuing novel product candidates in related mental health
disorders such as schizophrenia. Headquartered in the United States in Richmond, Va., Indivior employs more than 700
individuals globally and its portfolio is available in over 40
countries worldwide. Visit www.Indivior.com to learn more.
Forward-Looking Statements
This press release contains
forward-looking statements. We may, in some cases, use terms such
as "predicts," "believes," "potential," "proposed," "continue,"
"estimates," "anticipates," "expects," "plans," "intends," "may,"
"could," "might," "will," "should" or other words that convey
uncertainty of future events or outcomes to identify these
forward-looking statements. Forward-looking statements include,
among other things, statements regarding our financial guidance for
2015 and our medium- and long-term growth outlook, our operational
goals, our product development pipeline and statements regarding
ongoing litigation.
Various factors may cause differences between Indivior's
expectations and actual results, including: factors affecting sales
of Suboxone Tablet, Suboxone Film, Subutex Tablet and any future
products; the outcome of research and development activities;
decisions by regulatory authorities regarding the Indivior Group's
drug applications; the speed with which regulatory authorizations,
pricing approvals and product launches may be achieved; the outcome
of post-approval clinical trials; competitive developments;
difficulties or delays in manufacturing; the impact of existing and
future legislation and regulatory provisions on product
exclusivity; trends toward managed care and healthcare cost
containment; legislation or regulatory action affecting
pharmaceutical product pricing, reimbursement or access; claims and
concerns that may arise regarding the safety or efficacy of the
Indivior Group's products and product candidates; risks related to
legal proceedings; the Indivior Group's ability to protect its
patents and other intellectual property; the outcome of the
Suboxone Film patent litigation relating to the three ongoing ANDA
lawsuits; changes in governmental laws and regulations; issues
related to the outsourcing of certain operational and staff
functions to third parties; uncertainties related to general
economic, political, business, industry, regulatory and market
conditions; and the impact of acquisitions, divestitures,
restructurings, internal reorganizations, product recalls and
withdrawals and other unusual items.
Any forward-looking statements that we make in this press
release speak only as of the date of this press release. We assume
no obligation to update our forward-looking statements whether as a
result of new information, future events or otherwise, after the
date of this press release.
References
1 U.S. Department of Health and Human Services.
National Institutes of Health. National Institute of Mental Health.
Schizophrenia. NIH Publication No. 09-3517. Revised 2009.
2 Whiteford HA et al. Global burden of disease
attributable to mental and substance use disorders: Findings from
the Global Burden of Disease Study 2010. The Lancet. 382:
1575-1586 (2013).
3 Achilla E, McCrone P. The cost effectiveness of
long-acting/extended-release antipsychotics for the treatment of
schizophrenia: A systematic review of economic evaluations. Appl
Health Econ Health Policy. 11: 95–106 (2013).
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