Indivior | SUBLOCADE® Long-Term Safety Data Published in Journal of Clinical Psychopharmacology

– Indivior PLC (LON: INDV) today announced the publication of long-term safety data for SUBLOCADE® (buprenorphine extended-release) injection, for subcutaneous use (CIII). Slough, UK and Richmond, VA, April 16, 2020 The manuscript entitled "Treating Opioid Use Disorder with a Monthly Subcutaneous Buprenorphine Depot Injection: 12-month Safety, Tolerability and Efficacy Analysis" was published online on April 9, 2020 and will appear in an upcoming print issue of the Journal of Clinical Psychopharmacology.1 This open-label multicenter study (NCT 02510014) in adults with moderate or severe opioid use disorder (OUD) enrolled 257 participants from a previously conducted placebocontrolled, double-blind Phase III trial (Rollover group) and 412 De Novo participants not previously treated with SUBLOCADE. By study end, 60.7% participants completed the study and received up to 12 injections. The main findings were as follows: The safety profile of up to 12-month SUBLOCADE treatment was consistent with that of transmucosal buprenorphine, with the exception of the anticipated injection-site reactions.1 Overall, 66.8% of participants reported >1 treatment-emergent adverse event (TEAE). Injection-site TEAEs (13.2% of participants), were mostly mild or moderate in severity. An integrated analysis of the double-blind and open-label study participants showed that the incidence of TEAEs, including injection-site TEAEs, were lower in the second 6 months of treatment versus the first 6 months. There were no unexpected safety signals detected and no TEAEs potentially related to respiratory depression. The hepatic safety profile of SUBLOCADE was comparable to that reported for transmucosal buprenorphine and longer exposure to the highest 300 mg maintenance dose of SUBLOCADE did not worsen hepatic laboratory assessments. There were no cases of hepatocellular injury indicated by increased AST/ALT with jaundice and no removal of SUBLOCADE was required. Efficacy was evaluated using Urine Drug Screen for opioids plus self-reported illicit opioid use combined into a single endpoint. After 12 months of SUBLOCADE treatment, 61.5% of the Rollover participants and 75.8% of the De Novo participants were free of illicit opioid use. “Recent research has shown that treatment is most helpful when it addresses opioid use disorder as a chronic disease that requires services and support structures over an extended period of time,” said Christian Heidbreder, PhD, Indivior’s Chief Scientific Officer. “Data from this open-label study provide additional scientific evidence in support of the long-term safety profile of SUBLOCADE and may help clinicians to determine how best they can help patients achieve and maintain recovery.” ABOUT SUBLOCADE2 INDICATION AND USAGE SUBLOCADE® (buprenorphine extended-release) injection, for subcutaneous use (CIII) 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 a dose adjustment period for a minimum of seven days. SUBLOCADE should be used as part of a complete treatment program that includes counseling and psychosocial support. ABOUT SUBLOCADE2 INDICATION AND USAGE SUBLOCADE® (buprenorphine extended-release) injection, for subcutaneous use (CIII) 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 a dose adjustment period for a minimum of seven days. SUBLOCADE should be used as part of a complete treatment program that includes counseling and psychosocial support. IMPORTANT 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 selfadministration, 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. SUBLOCADE should only be prepared and administered by a healthcare provider. 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 SUBLOCADE 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 patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors. Addiction, Abuse, and Misuse: : Buprenorphine has been associated with life‐threatening respiratory depression, overdose, and death, particularly when misused by self-injection or with concomitant use of benzodiazepines or other CNS depressants, including alcohol. Warn patients of the potential danger of self-administration of benzodiazepines, other CNS depressants, opioid analgesics, and alcohol while under treatment with SUBLOCADE. Counsel patients that such medications should not be used concomitantly unless supervised by a healthcare provider. Risk of Life-Threatening Respiratory Depression and Concomitant Use of Benzodiazepines or Other CNS Depressants with Buprenorphine Use with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression). Opioids can cause sleep-related breathing disorders; e.g., central sleep apnea (CSA), sleeprelated 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. 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. Newborns should be observed for signs of NOWS and managed accordingly. Advise pregnant women receiving opioid addiction treatment with SUBLOCADE of the risk of neonatal opioid withdrawal syndrome. Neonatal Opioid Withdrawal Syndrome: Adrenal insufficiency has been reported with opioid use. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off the opioid. Adrenal Insufficiency: Due to the long-acting nature of SUBLOCADE, if treatment is discontinued, monitor patients for several months for withdrawal and treat appropriately. Discontinuation of SUBLOCADE Treatment: Inform patients that they may have detectable levels of buprenorphine for a prolonged period of time after treatment with SUBLOCADE. Considerations of drugdrug interactions, buprenorphine effects, and analgesia may continue to be relevant for several months after the last injection. : Because cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving buprenorphine, monitor liver function tests prior to treatment and monthly during treatment. Risk of Hepatitis, Hepatic Events Hypersensitivity to buprenorphine-containing products have been reported most commonly as rashes, hives, and pruritus. Some cases of bronchospasm, angioneurotic edema, and anaphylactic shock have also been reported. Hypersensitivity Reactions: Buprenorphine may precipitate opioid withdrawal signs and symptoms in persons who are currently physically dependent on full opioid agonists such as heroin, morphine, or methadone before the effects of the full opioid agonist have subsided. Verify that patients have tolerated and are dose adjusted on transmucosal buprenorphine before subcutaneously injecting SUBLOCADE. Precipitation of Opioid Withdrawal in Patients Dependent on Full Agonist Opioids: When patients need acute pain management, or may require anesthesia, treat patients receiving SUBLOCADE currently or within the last 6 months with a non-opioid analgesic whenever possible. If opioid therapy is required, patients may be treated with a high-affinity full opioid analgesic under the supervision of a physician, with particular attention to respiratory function, as higher doses may be required for analgesic effect and therefore, a higher potential for toxicity exists with opioid administration. Risks Associated With Treatment of Emergent Acute Pain: 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 physically dependent on an opioid and that the patient is being treated with SUBLOCADE. Because death has been reported for opioid naïve individuals who received buprenorphine sublingual tablet, SUBLOCADE is not appropriate for use in opioid naïve patients. Use in Opioid Naïve Patients: Because buprenorphine levels cannot be rapidly decreased, SUBLOCADE is not recommended for patients with preexisting moderate to severe hepatic impairment. Patients who develop moderate to severe hepatic impairment while being treated with SUBLOCADE should be monitored for several months for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine. Use in Patients With Impaired Hepatic Function: Buprenorphine has been observed to prolong the QTc interval in some patients participating in clinical trials. Avoid use of buprenorphine in patients with a history of Long QT Syndrome or an immediate family member with this condition or those taking Class IA antiarrhythmic medications (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, dofetilide), or other medications that prolong the QT interval. Use in Patients at Risk for Arrhythmia: SUBLOCADE 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 SUBLOCADE does not adversely affect their ability to engage in such activities. Impairment of Ability to Drive or Operate Machinery: Buprenorphine may produce orthostatic hypotension. Orthostatic Hypotension: 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. Buprenorphine can produce miosis and changes in the level of consciousness that may interfere with patient evaluation. Elevation of Cerebrospinal Fluid 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. Elevation of Intracholedochal Pressure: Buprenorphine may obscure the diagnosis or clinical course of patients with acute abdominal conditions. Effects in Acute Abdominal Conditions: Buprenorphine can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed to it. Unintentional Pediatric Exposure: Adverse reactions commonly associated with SUBLOCADE (≥5% of subjects) during clinical trials were constipation, headache, nausea, vomiting, increased hepatic enzymes, fatigue, and injection site pain and pruritus. This is not a complete list of potential adverse events. Please see the full Prescribing Information for a complete list. ADVERSE REACTIONS: DRUG INTERACTIONS Monitor patients starting or ending CYP3A4 inhibitors or inducers for potential over- or under-dosing. CYP3A4 Inhibitors and Inducers: If concomitant use with serotonergic drugs is warranted, monitor for serotonin syndrome, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Serotonergic Drugs: Consult the full Prescribing Information for SUBLOCADE for more information on potentially significant drug interactions. : Opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. USE IN SPECIFIC POPULATIONS Pregnancy : Buprenorphine passes into the mother’s milk. Advise breastfeeding women to monitor the infant for increased drowsiness and breathing difficulties. Fertility: Chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible. Lactation Monitor geriatric patients receiving SUBLOCADE for sedation or respiratory depression. Geriatric Patients: To report pregnancy or side effects associated with taking SUBLOCADE, please call 1-877- 782-6966. For more information about SUBLOCADE, see the full Prescribing Information including BOXED WARNING, and Medication Guide. For REMS information visit www. sublocadeREMS.com. About Opioid Use Disorder (OUD) Opioid addiction isn’t a moral weakness. Opioid addiction is a chronic disease called Opioid Use Disorder (OUD)3 in which people develop a pattern of using opioids that can lead to negative consequences.4 Opioid addiction may affect the parts of the brain that control impulses, judgment, and decision-making.4,5 Patients become trapped in a cycle of opioid use, which produces changes in brain function that can reduce their ability to control their use.4,6 In 2018, an estimated 10.3 million people aged 12 or older misused opioids in the past year, including 9.9 million prescription pain reliever misusers and 808,000 heroin users. Approximately 506,000 people misused prescription pain relievers and used heroin in the past year.7 SUBLOCADE is not indicated for use in children younger than 18 years of age. Buprenorphine, the active ingredient of SUBLOCADE can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed to it. Indivior is a global pharmaceutical company working to help change patients’ lives by developing medicines to treat addiction 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 cooccurring disorders of addiction. Indivior is dedicated to transforming addiction from a global human crisis to a recognized and treated chronic disease. Building on its global portfolio of opioid dependence 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 addiction, including alcohol use disorder. Headquartered in the United States in Richmond, VA, Indivior employs more than 800 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. About Indivior Media Contacts [email protected] +1 804-594-0836 US Tulchan Communications +44 207-353-4200 UK Jason Thompson Indivior Vice President, Investor Relations +1 804-402-7123 [email protected] Investor Contact

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