- Double-blind, placebo-controlled study aims to measure
safety and efficacy of INDV-2000 over 3 months in participants with
moderate to severe Opioid Use Disorder.
- INDV-2000 is an investigational non-opioid treatment that
acts through the orexin pathway, shown to play a key role in the
neurobiology of substance use disorder in animals.
- Recent animal studies have demonstrated that selective
Orexin-1 receptor antagonism can reduce self-administration of
opioids and synthetic opioids such as fentanyl and
remifentanil.
RICHMOND, Va., June 10,
2024 /PRNewswire/ -- Indivior PLC (LSE/Nasdaq:
INDV) today announced the dosing of the first subject with
INDV-2000 in a Phase 2 double-blind, placebo controlled,
randomized, dose-ranging study to assess the safety and efficacy of
INDV-2000 over 3 months in treatment-seeking individuals with
Opioid Use Disorder (OUD) (NCT06384157). The purpose of this
proof-of-concept study is to measure safety and efficacy and to
determine the dose-response relationship for INDV-2000 in
participants with moderate to severe OUD who are treatment-naïve,
have recently initiated or completed short-term medically
supervised opioid withdrawal with transmucosal (TM) buprenorphine,
and are interested in transitioning to a non-opioid treatment.
This milestone is another step in Indivior's mission to develop
new treatment options for patients with OUD and other substance use
disorders. With the support of an NIH-HEAL grant
(1R01DA043898-01A1) titled "Clinical Evaluation of INDV-2000
(C4X3256), a Non-Opioid, Highly Selective Orexin-1 Receptor
Antagonist for the Treatment of Opioid Use Disorder" the study
was initiated for the clinical development of INDV-2000, a potent
and selective oral orexin-1 receptor (OX1R) antagonist, with
demonstrated activity in rodent models of addiction and a safety
profile suitable for therapeutic administration in clinical
studies.1 More recently, animal studies also have
shown that selective antagonism of the OX1R can reduce heroin
intake and oxycodone self-administration2 and reduce the
consumption of synthetic opioids including remifentanil3
and fentanyl.4
"INDV-2000 provides Indivior with a unique opportunity to
further address unmet patient needs in the treatment of OUD with
potentially the first non-opioid orexin-targeted therapy," said
Christian Heidbreder, Chief
Scientific Officer. "By providing a potential therapeutic option
for patients who might benefit from a non-opioid alternative,
INDV-2000 may broaden the spectrum of care for OUD treatment."
The orexin-A and orexin-B neuropeptides are agonists of the
orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R),
respectively. The OX1R and OX2R are thought to play differential
physiological roles with the OX1R mainly involved in motivation and
reward and the OX2R in the modulation of the sleep/wake cycle and
energy homeostasis.3 The completion of clinical
Phase 1 Single Ascending Dose (NCT04413552) and Multiple Ascending
Dose (NCT04976855) studies happened after an end-of-Phase 1 meeting
with the FDA on November 3, 2023,
paving the way for the preparation and initiation of this clinical
Phase 2 proof-of-concept (PoC) study.
Opioid use disorder (OUD) involves disruption of brain circuits
engaged in reward, decision-making, learning, and self-control. The
magnitude of OUD worldwide highlights the need for novel
molecular entities ultimately translating into new medications for
the treatment of OUD. In the United
States, among people aged 12 or older in 2022, 3.2% (or 8.9
million people) misused opioids in the past year.5
"As the opioid epidemic continues to escalate, it is important
to develop more treatment options," said Dr. Heidbreder. "This
milestone highlights Indivior's commitment to developing a wider
range of therapeutics in both the opioid and non-opioid treatment
category, ultimately providing more choices for the patient."
About the Study
The purpose of this Phase 2 study is to measure safety and
efficacy and to determine the dose-response relationship for
INDV-2000 in participants with moderate to severe Opioid Use
Disorder (OUD) who are new to treatment, have recently initiated or
completed short-term medically supervised opioid withdrawal with
TM buprenorphine, and are interested in transitioning to a
non-opioid treatment.
On Day 1, trial participants will be randomized to the INDV-2000
or placebo group and receive the treatment in conjunction with TM
buprenorphine until Day 7. From Day 8 onward, INDV-2000 or placebo
will be administered as a standalone. The randomized treatment
period starts when the participant receives randomized treatment
(at Day 1) and ends at his/her last study visit after 3 months on
INDV-2000 or placebo. Alternatively, the treatment period ends when
participants initiate buprenorphine rescue therapy due to a relapse
in illicit opioid use.
About Indivior
Indivior is a global pharmaceutical company working to help
change patients' lives by developing medicines to treat substance
use disorders (SUD), opioid overdose and serious mental illnesses.
Our vision is that all patients around the world will have access
to evidence-based treatment for the chronic conditions and
co-occurring disorders of SUD. Indivior is dedicated to
transforming SUD from a global human crisis to a recognized and
treated chronic disease. Building on its global portfolio of opioid
use disorder treatments, Indivior has a pipeline of product
candidates designed to both expand on its heritage in this category
and potentially address other chronic conditions and cooccurring
disorders of SUD. Headquartered in the
United States in Richmond,
VA, Indivior employs more than 1,100 individuals globally
and its portfolio of products is available in 37 countries
worldwide. Visit www.indivior.com to learn more. Connect with
Indivior on LinkedIn by visiting
www.linkedin.com/company/indivior.
Important Cautionary Note Regarding Forward-Looking
Statements
This news release contains certain statements that are
forward-looking. Forward-looking statements include, among other
things, statements regarding potential new productor or
therapies, express or implied statements about their safety and
efficacy, and other statements containing the words "believe",
"anticipate", "plan", "expect", "intend", "estimate", "forecast,"
"strategy," "target," "guidance," "outlook," "potential",
"project", "priority," "may", "will", "should", "would", "could",
"can", "outlook," "guidance", the negatives thereof, and variations
thereon and similar expressions. By their nature, forward-looking
statements involve risks and uncertainties as they relate to events
or circumstances that may or may not occur in the future.
Actual results may differ materially from those expressed or
implied in such statements because they relate to future events.
Various factors may cause differences between Indivior's
expectations and actual results, including, among others, the risk
that the clinical trial may fail to demonstrate the safety or
efficacy of the treatment; that the FDA will require one or more
Phase 3 trials before approving INDV-2000 for individuals with
opioid use disorder; that the FDA may decline to approve INDV-2000
for individuals with opioid use disorder for many other reasons;
and the material risks described in the most recent Indivior
PLC Annual Report and in subsequent releases.
Forward-looking statements speak only as of the date that they
are made and should be regarded solely as our current plans,
estimates and beliefs. Except as required by law, we do not
undertake and specifically decline any obligation to update,
republish or revise forward-looking statements to reflect future
events or circumstances or to reflect the occurrences of
unanticipated events.
References
- Murray CM, Fox JC, Heidbreder C, Young M. A Novel, Non-Opioid, Selective
Orexin-1 Receptor Antagonist for the Treatment of
Substance Use Disorders. Neuroscience Applied, Volume 3, 2024,
104053. https://doi.org/10.1016/j.nsa.2024.104053. Epub ahead of
print.
- Smith, R.J., Aston-Jones, G., 2012. Orexin / hypocretin 1
receptor antagonist reduces heroin self-administration and
cue-induced heroin seeking. Eur. J. Neurosci. 35, 798–804.
https://doi.org/10.1111/j.1460-9568.2012.08013.x
- Mohammadkhani, A., James, M.H., Pantazis, C.B., Aston-Jones,
G., 2020. Persistent effects of the orexin-1 receptor antagonist
SB-334867 on motivation for the fast-acting opioid remifentanil.
Brain Res. 1731:146461.
https://doi.org/10.1016/j.brainres.2019.146461
- Fragale, J E., Pantazis, C.B., James, M.H., and Aston-Jones,
G., 2019. The role of orexin-1 receptor signaling in demand for the
opioid fentanyl. Neuropsychopharmacology. 44, 1690–1697.
https://doi.org/10.1038/s41386-019-0420-x
- Substance Abuse and Mental Health Services Administration.
(2022) Highlights for the 2022 National Survey on Drug Use and
Health1. Retrieved from Highlights for the 2022 National Survey on
Drug Use and Health (samhsa.gov)
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SOURCE Indivior PLC