REG - Indivior PLC - Buprenorphine-Fentanyl Interaction Study Results

IndiviorAnnouncement

28/01/2022 07:00

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20220128:nRSb9160Za&default-theme=true

RNS Number : 9160Z  Indivior PLC  28 January 2022

Research Indicates Sustained High Plasma Concentrations of Buprenorphine
Reduce

Fentanyl-Induced Respiratory Depression in Opioid-Tolerant Participants

 

Indivior Announces Publication of Results from Buprenorphine-Fentanyl
Interaction Study

in PLOS ONE Peer-Reviewed Journal

 

Slough, UK, and Richmond, VA, January 28, 2022 - Indivior PLC, (LON: INDV)
today announced the publication of data from a clinical pharmacology study
designed to assess the ability of buprenorphine to reduce respiratory
depression and apnea associated with escalating doses of fentanyl administered
in a clinical setting. The manuscript entitled "Effect of sustained high
buprenorphine plasma concentrations on fentanyl-induced respiratory
depression: a placebo-controlled crossover study in healthy volunteers and
opioid-tolerant patients," was published online
(https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256752) on
January 27, 2022, and will appear in an upcoming print issue of PLOS ONE.(1)
 

 

Provisional data from the Centers for Disease Control and Prevention (CDC)
estimate there were 101,263 predicted drug overdose deaths in the U.S. during
the 12-month period ending June 2021, with approximately 76,002 and 64,977 of
these deaths attributable to opioids and synthetic opioids (excluding
methadone), respectively.2 The majority of opioid-related overdose deaths in
the US are the result of synthetic opioids (mainly fentanyl and illicit
fentanyl analogs) that are more potent than heroin and that can unexpectedly
cause respiratory depression by being ingested as a substitute for heroin or
with drugs such as prescription opioids, cocaine, methamphetamine or
nonopioids with sedative or hypnotic properties (e.g., benzodiazepines,
gabapentin, and xylazine).(3,4,5 6)

 

"The nation's drug overdose epidemic is now largely driven by illicit fentanyl
and fentanyl analogs, often in combination or in adulterated forms, posing an
even greater risk of overdose to people struggling with addiction,(7)" said
Mark Crossley, Chief Executive Officer, Indivior. "In the 12-month period
ending in June 2021, 75 percent of the estimated 101,000 drug overdose deaths
were driven by opioids(2) - an average of more than 200 deaths per day, double
the number of fatalities resulting from motor vehicle traffic crashes.(8)"

 

This clinical pharmacology study, which was conducted in a medical center
anesthesiology department, was designed to assess the competitive interaction
of fentanyl and buprenorphine on respiratory depression. It evaluated the
ability of treatment-relevant plasma concentrations of buprenorphine to
prevent respiratory depression and resultant apnea (cessation of breathing)
induced by escalating doses of fentanyl.

 

The primary endpoint of the study was to measure the effects of escalating
fentanyl dosing on respiratory depression as measured by minute ventilation
(VE) under elevated carbon dioxide (CO2) conditions. VE is the volume of gas
inhaled or exhaled from a person's lungs per minute. VE is an important
parameter in respiratory medicine due to its relationship with blood carbon
dioxide (CO2) levels.

 

The maximum decrease in VE, induced by the highest dose of fentanyl, was
nearly 60 percent less with a steady-state plasma buprenorphine concentration
of 2.0 ng/mL compared with placebo (33.7 percent vs 82.3 percent decrease in
VE, respectively). The risk of experiencing apnea requiring verbal stimulation
after fentanyl dosing was significantly lower with buprenorphine than with
placebo (p=0.001).(1)

 

"The results of this proof-of-principle study increase our understanding of
the role high sustained buprenorphine plasma concentrations may have in
reducing fentanyl-induced respiratory depression," said Christian Heidbreder,
PhD, Chief Scientific Officer, Indivior. "Future research is warranted to
assess the competitive interaction of buprenorphine and fentanyl (as well as
other illicitly manufactured fentanyl analogs) as we continue to deepen our
understanding of buprenorphine as an evidence-based treatment for patients
struggling with opioid use disorder."

 

In June of 2021, the US Food and Drug Administration (FDA) approved a label
update for SUBLOCADE® (buprenorphine extended release) injection, for
subcutaneous use (CIII)(9), to include data from this clinical pharmacology
study in Section 12.2 Pharmacodynamics; Pharmacodynamic Interaction with
Fentanyl.(1)

 

About SUBLOCADE®(9)

SUBLOCADE (buprenorphine extended release) injection, for subcutaneous use
(CIII)

INDICATION AND HIGHLIGHTED SAFETY INFORMATION

 

INDICATION

SUBLOCADE is indicated for the treatment of moderate to severe opioid use
disorder in patients who have initiated treatment with a transmucosal
buprenorphine-containing product, followed by dose adjustment for a minimum of
7 days.

 

SUBLOCADE should be used as part of a complete treatment plan that includes
counseling and psychosocial support.

 

HIGHLIGHTED SAFETY INFORMATION

WARNING: RISK OF SERIOUS HARM OR DEATH WITH INTRAVENOUS ADMINISTRATION;
SUBLOCADE RISK EVALUATION AND MITIGATION STRATEGY

 

•     Serious harm or death could result if administered intravenously.
SUBLOCADE

        forms a solid mass upon contact with body fluids and may cause
occlusion,

        local tissue damage, and thrombo-embolic events, including life
threatening

        pulmonary emboli, if administered intravenously.

 

•     Because of the risk of serious harm or death that could result
from intravenous

        self-administration, SUBLOCADE is only available through a
restricted program called

the SUBLOCADE REMS Program. Healthcare settings and pharmacies that order and

dispense SUBLOCADE must be certified in this program and comply with the REMS

requirements.

 

 

Prescription use of this product is limited under the Drug Addiction Treatment
Act.

 

CONTRAINDICATIONS

SUBLOCADE should not be administered to patients who have been shown to be
hypersensitive to buprenorphine or any component of the ATRIGEL® delivery
system

 

WARNINGS AND PRECAUTIONS

Addiction, Abuse, and Misuse: SUBLOCADE contains buprenorphine, a Schedule III
controlled substance that can be abused in a manner similar to other opioids.
Monitor patients for conditions indicative of diversion or progression of
opioid dependence and addictive behaviors.

 

Respiratory Depression: Life threatening respiratory depression and death have
occurred in association with buprenorphine. Warn patients of the potential
danger of self-administration of benzodiazepines or other CNS depressants
while under treatment with SUBLOCADE.

 

Opioids can cause sleep-related breathing disorders e.g., central sleep apnea
(CSA), sleep-related hypoxemia. Opioid use increases the risk of CSA in a
dose-dependent fashion. Consider decreasing the opioid using best practices
for opioid taper if CSA occurs.

 

Strongly consider prescribing naloxone at SUBLOCADE initiation or renewal
because patients being treated for opioid use disorder have the potential for
relapse, putting them at risk for opioid overdose. Educate patients and
caregivers on how to recognize respiratory depression and how to treat with
naloxone if prescribed.

Risk of Serious Injection Site Reactions: The most common injection site
reactions are pain, erythema and pruritis with some involving abscess,
ulceration, and necrosis. The likelihood of serious injection site reactions
may increase with inadvertent intramuscular or intradermal administration.

 

Neonatal Opioid Withdrawal Syndrome: Neonatal opioid withdrawal syndrome is an
expected and treatable outcome of prolonged use of opioids during pregnancy.

 

Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of
corticosteroids, and wean patient off the opioid.

 

Risk of Opioid Withdrawal With Abrupt Discontinuation: If treatment with
SUBLOCADE is discontinued, monitor patients for several months for withdrawal
and treat appropriately.

 

Risk of Hepatitis, Hepatic Events: Monitor liver function tests prior to and
during treatment.

 

Risk of Withdrawal in Patients Dependent on Full Agonist Opioids: Verify that
patient is clinically stable on transmucosal buprenorphine before injecting
SUBLOCADE.

 

Treatment of Emergent Acute Pain: Treat pain with a non-opioid analgesic
whenever possible. If opioid therapy is required, monitor patients closely
because higher doses may be required for analgesic effect.

 

ADVERSE REACTIONS

Adverse reactions commonly associated with SUBLOCADE (in ≥5% of subjects)
were constipation, headache, nausea, injection site pruritus, vomiting,
increased hepatic enzymes, fatigue, and injection site pain.

 

For more information about SUBLOCADE, the full Prescribing Information
including BOXED WARNING, and Medication Guide, visit www.sublocade.com
(http://www.sublocade.com) .

 

 

About Opioid Use Disorder (OUD)

Opioid Use Disorder (OUD) is a chronic disease in which people develop a
pattern of using opioids that can lead to negative consequences.(10) OUD may
affect the parts of the brain that are necessary for life-sustaining
functions.(10)

( )

About Indivior

Indivior is a global pharmaceutical company working to help change patients'
lives by developing medicines to treat substance use disorders (SUD) 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 OUD 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 co-occurring disorders of
SUD, including alcohol use disorder and cannabis use disorder. Headquartered
in the United States in Richmond, VA, Indivior employs more than 900
individuals globally and its portfolio of products is available in over 40
countries worldwide. Visit www.indivior.com to learn more. Connect with
Indivior on LinkedIn by visiting www.linkedin.com/company/indivior
(http://www.linkedin.com/company/indivior) .

 

Forward-Looking Statements

This announcement contains certain statements that are forward-looking. 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. Forward-looking
statements include, among other things, statements regarding the Indivior
Group's financial guidance for 2021, and its medium- and long-term growth
outlook, its operational goals, its product development pipeline and
statements regarding ongoing litigation and other statements containing the
words "subject to", "believe", "anticipate", "plan", "expect", "intend",
"estimate", "project", "may", "will", "should", "would", "could", "can", the
negatives thereof, variations thereon and similar expressions.

Various factors may cause differences between Indivior's expectations and
actual results, including, among others (including those described in the risk
factors described in the most recent Indivior PLC Annual Report and in
subsequent releases): factors affecting sales of Indivior Group's products and
financial position; the outcome of research and development activities;
decisions by regulatory authorities regarding the Indivior Group's drug
applications or authorizations; the speed with which regulatory
authorizations, pricing approvals and product launches may be achieved, if at
all; the outcome of post-approval clinical trials; competitive developments;
difficulties or delays in manufacturing and in the supply chain; disruptions
in or failure of information technology systems; 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;
challenges in the commercial execution; 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, including compliance with the
U.S. Department of Justice Resolution and Settlement Agreements, noncompliance
with which could result in potential exclusion from participating in U.S.
Federal health care programs; the ongoing investigative and antitrust
litigation matters; the opioid national multi-district litigation and
securities class action litigation; the Indivior Group's ability to protect
its patents and other intellectual property; the outcome of patent
infringement litigation relating to Indivior Group's products, including the
ongoing ANDA lawsuits; changes in governmental laws and regulations; issues
related to the outsourcing of certain operational and staff functions to third
parties; risks related to the evolving COVID-19 pandemic and the potential
impact of COVID-19 on the Indivior Group's operations and financial condition,
which cannot be predicted with confidence; 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.

Consequently, 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. You should not place undue reliance on forward-looking statements. We
cannot guarantee future results, events, levels of activity, performance or
achievements. 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.

 

Media Contacts:

UK

Tulchan Communications

+44 207-353-4200

 

US

IndiviorMediaContacts@indivior.com (mailto:IndiviorMediaContacts@indivior.com)
 

+1 804-594-0836

 

Jason Thompson

Vice President, Investor Relations

Indivior PLC (LON: INDV)

Mobile: 804-402-7123

 

References:

1.     Moss, L, et al. Effect of sustained high buprenorphine plasma
concentrations on fentanyl-induced respiratory depression: a
placebo-controlled crossover study in healthy volunteers and opioid-tolerant
patients 2021.

2.     https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
(https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm) .  Accessed
=January 14, 2021.

3.   Volkow, N.D. The epidemic of fentanyl misuse and overdoses: challenges
and strategies. World Psychiatry. 2021. 20:
195-196. https://doi.org/10.1002/wps.20846
(https://doi.org/10.1002/wps.20846) .

 

4.     Dolinak, D, et al. Opioid Toxicity. Acad Forensic Pathol. 2017;
(1): 19-35. doi: 10.23907/2017.003

 

5.    Ochalek  TA, Parker MA, Higgings ST, et al. Fentanyl exposure among
patients seeking opioids treatments. J Subst Abuse Treat 2019; 96: 23-25. doi:
10.1016/j.jsat.2018.10.007

 

6.    O'Donnell J, Tanz LJ, Gladden RM, Davis NL, Bitting J. Trends in and
Characteristics of Drug Overdose Deaths Involving Illicitly Manufactured
Fentanyls - United States, 2019-2020. MMWR Morb Mortal Wkly Rep
2021;70:1740-1746. DOI: DOI: Trends in and Characteristics of Drug Overdose
Deaths Involving Illicitly Manufactured Fentanyls - United States, 2019-2020 |
MMWR (cdc.gov)
(https://www.cdc.gov/mmwr/volumes/70/wr/mm7050e3.htm?s_cid=mm7050e3_w)

 

7.
https://www.ama-assn.org/system/files/issue-brief-increases-in-opioid-related-overdose.pdf
(https://www.ama-assn.org/system/files/issue-brief-increases-in-opioid-related-overdose.pdf)
. Accessed September 6, 2021.

 

8.     https://crashstats.nhtsa.dot.gov/Api/Public/ViewPublication/813115
(https://crashstats.nhtsa.dot.gov/Api/Public/ViewPublication/813115) .
Accessed September 10, 2021.

9.     SUBLOCADE® [Prescribing Information]. Indivior Inc., North
Chesterfield, VA. June 2021.

10.  U.S. Department of Health and Human Services (HHS), National Institute
on Drug Abuse, National Institutes of Health. Drugs, Brains, and Behavior: The
Science of Addiction. HHS Publication No. (SMA) 18-5063PT5, Printed 2018.

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCBRMJTMTMTTPT