PLYMOUTH
MEETING, Pa., June 25,
2024 /PRNewswire/ -- Braeburn Inc. announces the
publication of a post hoc analysis in the Journal of the
American Medical Association (JAMA) Network Open. The analysis
evaluated data in patients with evidence of fentanyl use from the
Phase 3 Clinical Efficacy and Safety trial comparing BRIXADI
(buprenorphine) extended-release injection for subcutaneous use
(CIII) to daily sublingual buprenorphine/naloxone (SL BPN/NX) in
patients with moderate to severe opioid use disorder (OUD).
"Fentanyl is a primary driver of the continued growth of the
opioid epidemic. The findings support prior observational studies
that buprenorphine is effective against fentanyl, and is consistent
with evidence from the BRIXADI Phase 3 Study," said Edward V. Nunes, M.D., Professor of Psychiatry,
Columbia University Irving Medical
Center Department of Psychiatry. "Further research is needed to
assess the efficacy of medications for OUD in the current
landscape."
The Phase 3, 24-week, randomized, double-blind, double-dummy
active-controlled, multicenter, study was conducted at 35 US
outpatient clinical centers. The post hoc analysis included a
subgroup of 123 participants (BRIXADI, n=64; SL BPN/NX, n=59) who
had evidence of baseline fentanyl use. The Phase 3 trial was
designed to include participants characteristic of the patient
population with moderate to severe OUD.
Key highlights of the Post Hoc Analysis:
- Assessments in this analysis included urine toxicology for
illicit opioid use including fentanyl, Clinical Opiate
Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS),
Visual Analog Scale (VAS), and adverse events (AEs).
- In the fentanyl-positive subgroup, the mean percentage of
urine samples negative for fentanyl during the study was 74.6% for
the BRIXADI arm versus 61.9% for SL BPN/NX.
- In the fentanyl-positive subgroup, the mean percentage of
urine samples negative for opioids was 28.5% for the BRIXADI arm
versus 18.8% for SL BPN/NX. Similarly, in the fentanyl-negative
subgroup, the mean percentage of urine samples negative for opioids
was 36.7% for BRIXADI versus 30.6% in the SL BPN/NX arm.
- No substantial variance was observed in rates of study
completion between fentanyl-positive and fentanyl-negative
subgroups (60.2% and 56.7%, respectively).
- With the exception of injection-site AEs such as swelling,
inflammation, and induration, the observed AEs from this analysis
were consistent with the known safety profile of BPN. Three
nonfatal heroin overdoses were reported overall: one in the
fentanyl-negative subgroup and two in the fentanyl-positive
subgroup, all occurred in patients receiving SL BPN/NX.
- Limitations of the post hoc analysis include that patients were
primarily using heroin mixed with fentanyl. The analysis was not
prespecified and the parent trial was not designed to assess the
differences in treatment response between the subgroups.
Differences in outcomes could be related to overall disease
severity rather than fentanyl use.
"This is the first study that evaluated data from patients
testing positive for fentanyl at baseline in a phase 3 trial
comparing the safety and effectiveness of long-acting buprenorphine
to SL BPN/NX for the treatment of OUD," remarked Natalie R. Budilovsky-Kelley, PharmD, Senior
Director, Medical Affairs at Braeburn. "These findings provide
additional information regarding treatment of patients with OUD who
are using fentanyl."1
The full publication "Extended-Release Injection vs Sublingual
Buprenorphine for Opioid Use Disorder with Fentanyl Use" is
available online at JAMA Network Open today.
"We are grateful to partner with researchers that share our
unwavering commitment to those impacted by OUD to address this
urgent public health crisis," remarked Joshua M. Cohen, MD, MPH, FAHS, Chief Medical
Officer at Braeburn. "Braeburn remains committed to furthering the
scientific understanding of the treatment of OUD."
About the Phase 3 Trial
The data were collected during
a 24-week, randomized, double-blind trial (NCT02651584) conducted
from December 2015 to November 2016 across 35 outpatient sites in
the United States. Patients were
randomized to daily SL placebo alongside BRIXADI weekly (first 12
weeks; Phase 1) and BRIXADI monthly (last 12 weeks; Phase 2);
or to daily SL BPN/NX (24 weeks) with matched weekly and monthly
subcutaneous placebo injections (SL-BPN/NX group). Of the 428
patients included in the study, more than 28% had evidence of
fentanyl use at baseline.
About BRIXADI®
INDICATIONS AND USAGE
BRIXADI
is indicated for the treatment of moderate to severe opioid
use disorder in patients who have initiated treatment with a single
dose of a transmucosal buprenorphine product or who are already
being treated with buprenorphine.
BRIXADI should be used as part of a complete treatment plan that
includes counseling and psychosocial support.
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF
SERIOUS HARM OR DEATH WITH INTRAVENOUS ADMINISTRATION; BRIXADI
RISK
EVALUATION AND MITIGATION STRATEGY
|
- Serious harm or death could result if
administered intravenously. BRIXADI forms a liquid crystalline
gel 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,
BRIXADI is only available through a restricted program called the
BRIXADI REMS. Healthcare settings and pharmacies that order and
dispense BRIXADI must be certified in this program and comply with
the REMS requirements.
|
BRIXADI (buprenorphine) extended-release injection (weekly, 50
mg/mL buprenorphine) and BRIXADI (monthly, 356 mg/mL buprenorphine)
are different formulations. Doses of BRIXADI (weekly) cannot be
combined to yield an equivalent monthly dose.
BRIXADI is contraindicated in patients with
hypersensitivity (e.g. anaphylactic shock) to buprenorphine or any
other ingredients in the solution for injection.
WARNINGS AND PRECAUTIONS
Addiction, Abuse, and
Misuse: BRIXADI contains buprenorphine, a Schedule III
controlled substance that can be abused in a manner similar to
other opioids. Buprenorphine is sought by people with opioid use
disorder and is subject to criminal diversion. Monitor all patients
for progression of opioid dependence and addictive
behaviors.
Respiratory and CNS Depression: Buprenorphine has been
associated with life-threatening respiratory depression and death.
Use BRIXADI with caution in patients with compromised respiratory
function. Due to its extended-release characteristics, if BRIXADI
is discontinued as a result of compromised respiratory function,
monitor patients for ongoing buprenorphine effects for
approximately 1 month for BRIXADI (weekly) and for approximately 4
months for BRIXADI (monthly). Educate patients and caregivers on
how to recognize respiratory depression and emphasize the
importance of calling 911 or getting emergency medical help right
away in the event of a known or suspected overdose.
Patient Access to Naloxone for the Emergency Treatment of
Opioid Overdose: Discuss the availability of naloxone for the
emergency treatment of opioid overdose with the patient and
caregiver. Because patients being treated for opioid use disorder
have the potential for relapse, putting them at risk for opioid
overdose, strongly consider prescribing naloxone for the emergency
treatment of opioid overdose, both when initiating and renewing
treatment with BRIXADI. If naloxone is prescribed, educate patients
and caregivers on how to treat with naloxone, and emphasize the
importance of calling 911 or getting emergency medical help, even
if naloxone is administered.
Concomitant Use of Benzodiazepines or other CNS
Depressants: Concomitant use of buprenorphine and
benzodiazepines or other CNS depressants increase the risk of
adverse reactions including respiratory depression, overdose and
death. Ensure that other healthcare providers prescribing
benzodiazepines or other CNS depressants are aware of the patient's
buprenorphine treatment and coordinate care to minimize the risk
associated with concomitant use. Inform patients and caregivers
that potentially fatal additive effects may occur if BRIXADI is
used with benzodiazepines or other CNS depressants, including
alcohol, and not to use these concomitantly unless supervised by a
healthcare provider.
Neonatal Opioid Withdrawal Syndrome, Pregnancy, and
Lactation: Neonatal opioid withdrawal syndrome (NOWS) is an
expected and treatable outcome of prolonged use of opioids during
pregnancy. NOWS may be life-threatening if not recognized and
treated in the neonate. Healthcare providers should observe
newborns for signs of NOWS and manage accordingly. Advise pregnant
women receiving opioid addiction treatment with BRIXADI of the risk
of neonatal opioid withdrawal syndrome. Warn patients that
buprenorphine passes into breast milk. Advise the nursing mother
taking buprenorphine to monitor the infant for increased drowsiness
and breathing difficulties.
Adrenal Insufficiency: If adrenal insufficiency is
diagnosed, treat with physiologic replacement of corticosteroids,
and wean patient off of the opioid.
Risk of Opioid Withdrawal with Abrupt Discontinuation:
Patients who elect to discontinue BRIXADI treatment should be
monitored for withdrawal signs and symptoms with consideration
given to the product's extended-release characteristics.
Risk of Hepatitis, Hepatic Events, and Use in Patients with
Impaired Hepatic Function: Liver function tests should be
performed on all patients prior to initiation, during treatment,
and if a hepatic event is suspected. Because buprenorphine levels
cannot be rapidly decreased, patients with pre–existing moderate to
severe hepatic impairment are not candidates for treatment with
BRIXADI. Patients who develop moderate to severe hepatic impairment
while being treated with BRIXADI should be monitored for signs and
symptoms of toxicity or overdose of buprenorphine and may require a
dose adjustment.
Hypersensitivity Reactions: Cases of bronchospasm,
angioneurotic edema, and anaphylactic shock have been reported in
patients receiving buprenorphine-containing products. The most
common signs and symptoms include rashes, hives, and pruritus. The
BRIXADI needle cap is synthetically derived from natural rubber
latex which may cause allergic reactions in latex-sensitive
individuals.
Precipitation of Opioid Withdrawal in Patients Dependent on
Full Opioid Agonists: BRIXADI injection may precipitate opioid
withdrawal signs and symptoms in individuals physically dependent
on full opioid agonists such as heroin, morphine, or methadone
before the effects of the full opioid agonist have subsided. In
patients who are new entrants to treatment, to avoid precipitating
an opioid withdrawal syndrome, administer a 4 mg test dose of
transmucosal buprenorphine when objective signs of mild to moderate
withdrawal appear and monitor for precipitated withdrawal before
injecting BRIXADI.
Risks Associated with Treatment of Emergent Acute
Pain: While on BRIXADI, situations may arise where
patients need acute pain management, or may require anesthesia.
Treat patients receiving BRIXADI with non-opioid analgesic whenever
possible. Patients requiring opioid therapy for analgesia may be
treated with a high-affinity full opioid analgesic under the
supervision of a healthcare provider, with particular attention to
respiratory function. Higher doses may be required for analgesic
effect. Therefore, a higher potential for toxicity exists with
opioid administration. Advise patients of the importance of
instructing their family members, in the event of emergency, to
inform the treating healthcare provider or emergency room staff
that the patient is being treated with BRIXADI.
Use in Opioid Naïve Patients: There have been reported
deaths of opioid naïve individuals who received a 2 mg dose of
buprenorphine as a sublingual tablet. BRIXADI is not appropriate
for use in opioid naïve patients.
Patients at Risk for Arrhythmia: Thorough QT studies with
buprenorphine products have demonstrated QT prolongation ≤ 15 msec.
This QTc prolongation effect does not appear to be mediated by hERG
channels. Based on these two findings, buprenorphine is unlikely to
be pro-arrhythmic when used alone in patients without risk factors.
The risk of combining buprenorphine with other QT-prolonging agents
is not known.
Impairment of Ability to Drive and Operate Machinery:
BRIXADI may impair the mental or physical abilities required for
the performance of potentially dangerous tasks such as driving a
car or operating machinery. Caution patients about driving or
operating hazardous machinery until they are reasonably certain
that BRIXADI does not adversely affect their ability to engage in
such activities.
Orthostatic Hypotension: Buprenorphine may produce
orthostatic hypotension in ambulatory patients.
Elevation of Cerebrospinal Fluid Pressure: Buprenorphine
may elevate cerebrospinal fluid pressure and should be used with
caution in patients with head injury, intracranial lesions, and
other circumstances when cerebrospinal pressure may be
increased.
Elevation of Intracholedochal Pressure: Buprenorphine has
been shown to increase intracholedochal pressure, as do other
opioids, and thus should be administered with caution to patients
with dysfunction of the biliary tract.
Effects in Acute Abdominal Conditions: Buprenorphine may
obscure the diagnosis or clinical course of patients with acute
abdominal conditions.
Unintentional Pediatric Exposure: Buprenorphine can cause
severe, possibly fatal, respiratory depression in children who are
accidentally exposed to it.
ADVERSE REACTIONS
Adverse reactions commonly
associated with BRIXADI administration (in ≥5% of patients) were
injection site pain, headache, constipation, nausea, injection site
erythema, injection site pruritus, insomnia, and urinary tract
infection.
To report SUSPECTED ADVERSE REACTIONS, contact Braeburn at
1-833-274-9234 or FDA at 1-800-FDA1088 or
www.fda.gov/medwatch.
Please see FULL PRESCRIBING INFORMATION, including
BOXED WARNING, and MEDICATION GUIDE.
About Braeburn
Braeburn is dedicated to delivering
solutions for people living with the serious consequences of opioid
use disorder. At Braeburn, we challenge the status quo and champion
transformation of the management of opioid use disorder (OUD) by
partnering with the community to create a world where every person
with OUD gets the best possible care and opportunity to reach their
full potential. Visit https://braeburnrx.com to learn more.
Connect with Braeburn on LinkedIn at
https://linkedin.com/company/Braeburn.
- Lofwall MR, Walsh SL, Nunes EV,
et al. Weekly and Monthly Subcutaneous Buprenorphine Depot
Formulations vs Daily Sublingual Buprenorphine With Naloxone for
Treatment of Opioid Use Disorder: A Randomized Clinical Trial.
JAMA Intern Med. 2018;178(6):764–773.
doi:10.1001/jamainternmed.2018.1052.
For additional information, please
contact:
Sabrina
Romano: SRomano@braeburnrx.com
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