Plymouth Meeting, Pa. -- May 23, 2023 -- Braeburn announces that the U.S. Food and Drug Administration (FDA) has approved Brixadi (buprenorphine) extended-release injection for subcutaneous use (CIII), a new weekly and monthly medication for moderate to severe opioid use disorder (OUD) in patients who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with a transmucosal buprenorphine-containing product. Brixadi should be used as part of a complete treatment plan that includes counseling and psychosocial support. Brixadi is to be administered only by healthcare providers in a healthcare setting and will be available in the U.S. in September 2023.

Brixadi is the first and only weekly and monthly subcutaneous injection for moderate to severe OUD and is the only buprenorphine injectable that utilizes FluidCrystal®* Injection Depot Technology. Patients currently being treated with oral buprenorphine-containing products can be switched to equivalent doses of Brixadi Weekly or Brixadi Monthly in accordance with the Prescribing Information for Brixadi.

“Today’s FDA approval of Brixadi is a significant step forward in the fight against OUD,” said Mike Derkacz, President and CEO of Braeburn. “Over the last three years the US experienced a significant increase in opioid overdoses in part related to the economic and social upheaval that negatively impacted all of us, especially people with opioid use disorder and people in recovery. Additional medication options for opioid use disorder will support healthcare providers in addressing the needs of their patients with opioid use disorder.”

Due to the risk of serious harm resulting from accidental intravenous (IV) administration, Brixadi has a Boxed Warning and will be made available through a restricted distribution program called the Brixadi Risk Evaluation and Mitigation Strategy (REMS). Healthcare settings and pharmacies that order and dispense Brixadi must be certified in this program and comply with the REMS requirements. Information on the Brixadi REMS program will be available at www.BrixadiREMS.com.

Brixadi is the only injectable buprenorphine studied against sublingual buprenorphine/naloxone (SL BPN/NX) in a 24-week Phase 3, double-blind study, which randomized 428 adults with moderate to severe OUD. The trial enrolled patients representative of the real-world population, including patients that injected opioids (52%), patients that primarily used heroin (71%), patients with evidence of fentanyl use (26%) and patients using nonopioid substances at screening (71%). In this pivotal Phase 3 efficacy and safety trial, weekly and monthly Brixadi met the primary endpoint of non-inferiority for responder rate versus daily SL BPN/NX (16.9% vs. 14.0%, respectively; p<0.001). Additionally, Brixadi demonstrated superiority to SL BPN/NX based on the cumulative distribution function (CDF) of the percentage of negative opioid assessments from week 4 through week 24 (p=0.004; secondary endpoint).

“A weekly and monthly buprenorphine injection with different dose options can align with clinical practice and patient care needs,” said Dr. Michelle Lofwall, Professor of Behavioral Science and Psychiatry at the University of Kentucky Center on Drug and Alcohol Research and Primary Investigator in the Phase 3 efficacy and safety study. “Some patients need help with taking their medication as prescribed, some prefer not taking a daily medication or visiting a pharmacy to pick up their medication, so having a weekly and monthly option that provides buprenorphine over one week or one month could benefit patients, their loved ones and the treatment providers.”

The safety profile of Brixadi was consistent with the known systemic safety profile of oral buprenorphine with the exception of mild-to-moderate injection-site reactions. The most common adverse reactions included injection-site pain, headache, constipation, nausea, injection-site erythema, injection-site pruritus, insomnia and urinary tract infections.

Brixadi is formulated using FluidCrystal® Injection Depot Technology, allowing for a low volume pre-filled syringe. Upon injection and contact with fluids in the tissue, the solution transforms into a nanostructured liquid-crystalline gel allowing for a slow release of buprenorphine at a steady rate over a one-week or one-month period. Brixadi is delivered with a 23-gauge needle and may be administered in the buttock, thigh, stomach (abdomen) or upper arm.** Brixadi does not require refrigeration.

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. 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. Healthcare providers should observe newborns for signs of NOWS and manage accordingly. Advise women that if they are pregnant while being treated with Brixadi, the baby may have signs of withdrawal at birth and that withdrawal is treatable. 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 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. 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.

Treatment of Emergent Acute Pain: 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. 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. The above guidance should also be considered for any patient who has been treated with Brixadi within the last 6 months.

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: 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.

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-FDA-1088 or www.fda.gov/medwatch.

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 help 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.

Source: Braeburn Inc.

Posted: May 2023