INDIVIOR PLC

Substance Use and its Impact

According to the United Nations Office on Drugs and Crime World Drug Report 2022, World Drug Report 2024, there number of people who use drugs globally has risen to 292 million in 2022, a 20% increase over 10 years.

People who use drugs regularly are likely to experience negative health consequences. They are also more at risk of contracting infectious diseases such as HIV and hepatitis C, and to experience overdose and suffer premature death. Furthermore, an association exists between SUD and co-occurring or comorbid mental health disorders (for example, depression, anxiety or psychosis). There is also an association between SUD and socioeconomic disadvantage, low educational attainment, increased difficulty in finding and remaining in employment, and financial instability and poverty.

World Health Organization’s (WHO)Global Status Report on Alcohol and Health and Treatment of Substance Use Disorders published in June 2024 reported that 2.6 million deaths per year globally were attributable to alcohol consumption, accounting for 5% of all deaths, and 0.6 million deaths to psychoactive drug use.

The threat SUD poses to global health has long been recognized, and as such strengthening the prevention and treatment is included in the United Nations’ Sustainable Development Goals for 2030.

Overdose deaths continue to be significant in the U.S. According to the latest data from the U.S. Center for Disease Control & Prevention (CDC) there were 97,000 fatal overdoses over the previous 12-month period ending July 2024 of which 67,952 were linked to natural and synthetic opioids

Substance Use Disorder: The Disease

Substance Use Disorder ("SUD”) has been described as a “medical disorder that affects the brain and changes behavior.” Various substances may be involved including alcohol, illicit drugs, prescription medications, and even some over-the-counter medicines.

The National Institute on Drug Abuse ("NIDA”), the Substance Abuse and Mental Health Services Administration ("SAMHSA") and the National Institutes of Health ("NIH”) all describe SUD as a long-term and relapsing condition characterized by the individual compulsively seeking and using drugs despite adverse consequences.

Since SUD is marked by periods of recovery and symptom recurrence, or relapse, it resembles other chronic diseases like hypertension and type-2 diabetes. These diseases are lifelong conditions that require continual effort to manage. Symptoms will likely return during periods where treatment compliance is low or absent, and symptoms will likely diminish when compliance to treatment begins again in earnest.

In 2023, 48.5 million people aged 12 or older (or 17%) had a substance use disorder (SUD) in the past year, including 28.9 million who had an alcohol use disorder (AUD), 27.2 million who had a drug use disorder (DUD), and 7.5 million people who had both an AUD and a DUD, according to SAMHSA’s 2023 Survey on Drug Use and Health.

There is no single cause of SUD; people begin using substances for many reasons and one person’s path to addiction may look drastically different from that of another. The prevailing view is that no one thing can predict someone’s risk of developing a SUD—rather, the interaction of the person’s unique biology and their environment influences how the drug will impact a person’s susceptibility to becoming addicted.

Opioid Use Disorder

Opioids are a major concern in many countries because of the severe health consequences associated with their use, including non-fatal and fatal overdose.

OUD is a growing global public health crisis which still carries significant stigma in many countries. OUD is often perceived as a moral failing and sign of personal weakness rather than a chronic and relapsing disease affecting the brain that can be managed and responds to treatment. As a consequence, we believe coherent action to deal with sufferers and addiction is generally lacking.

According to the United Nations' World Drug Report 2024, an estimated 60 million people used opioids in 2022, representing 1% of the global population. In 2022, opioid use in North America remains high, with 3% of the adult population reporting past-year use (9 million users).

In addition, the number of deaths from opioid overdose in the U.S. continues to remain high, twice the level just a decade ago. The majority of opioid-related overdose deaths in the U.S. are now the result of fentanyl being ingested as a substitute for heroin or with drugs such as cocaine and methamphetamine that had been adulterated, or “cut,” with the opioid. Fentanyl is 30 to 50 times more potent than heroin and can cause rapid and profound respiratory depression. Individuals may not be aware that they have been exposed to fentanyl-laced drugs including heroin, prescription opioids, or psychostimulants.

Against the context of the dramatic rise in deaths from opioid overdose, Indivior is doing more to understand the interaction between fentanyl and buprenorphine. According to a peer-reviewed study conducted by the University of Leiden in Leiden, Netherlands and completed in 2019, sustained high-plasma concentrations of buprenorphine (similar to those provided by SUBLOCADE at steady-state) significantly reduced fentanyl-induced respiratory depression in opioid-tolerant participants.

The European market is smaller than the U.S. market with an estimated 860,000 high-risk opioid users, according to the European Union Drugs Agency European Drug Report 2024. The report also found that opioid use was reported as the main reason for entering specialist drug treatment by 63,000 clients in 2022, representing 25% of all those entering drug treatment in Europe.

According to the Australian Institute of Health and Welfare, in 2023 on an average day, 53,300 clients received pharmacotherapy treatment for their OUD across Australia. There is increasing awareness among healthcare providers in Australia of the misuse of opioid analgesics and the need for treatment. Recent policy changes to address this concern in Australia include re-classifying products containing Codeine so that they must be dispensed by a pharmacist rather than being available over the counter.

Similarly, according to the Canadian Centre on Substance Use and Addiction, approximately 10% of Canadian adults who used opioid medications, or 351,000 persons, reported problematic use, and approximately 153,000 are in treatment according to data from IQVIA (a health information provider). Outside of the U.S., Canada, and Australia, approximately 269 million people aged 15 to 64 suffer from drug use disorders or drug dependence, according to the United Nations Office on Drugs and Crime. Treatment services are generally very underdeveloped (with the exception of Australia and New Zealand), the key challenge being to convince governments to treat addiction as a chronic medical disease rather than a social disorder.

Treatment for Opioid Use Disorder

Medication for opioid use disorder ("MOUD") is the use of medications, in combination with counseling and behavioral therapies, to provide a “whole patient” approach to the treatment of OUD. Medications used in MOUD are approved by the FDA and MOUD programs are clinically driven and tailored to meet each patient’s needs.

Research shows that a combination of medication and psychosocial support can successfully treat these disorders, and for some people struggling with addiction, MOUD can help sustain recovery. MOUD is also used to prevent or reduce opioid overdose.

MOUD is primarily used for the treatment of addiction to opioids such as heroin and prescription pain relievers that contain opiates. The prescribed medication normalizes brain chemistry, blocks the euphoric effects of opioids, relieves physiological cravings, and normalizes body functions without the negative and euphoric effects of the substance. MOUD has been shown to be more effective than medication or counseling alone in treating OUD.

A common misconception about MOUD is that some of the medicines used simply substitute one drug for another. However, these medications may restore healthy brain function, which leads to improvements in behaviors associated with addiction. Longer-term use of these medications is associated with improved outcomes.

Treatment methods in the EU differ from those in the U.S. While U.S. patients can obtain a 30-day prescription and self-administer treatment, such as SUBOXONE Film, prescribed by a treating physician, supervised dosing in the EU requires a daily visit to the clinic for many patients. Methadone and generics are also generally more broadly available as social funding puts pressure on prices, and treatment is more highly regulated. However, the harm reduction mindset is now changing towards recovery and the EU has begun to recognize the need to implement treatment systems that allow patients to return to a more normal lifestyle.

Treatment access

Despite the prevalence of SUD, including opioid misuse, and the existence of effective treatments, including medication for opioid use disorder, most people who need treatment do not seek or receive it. In 2022, an estimated 4% of U.S. adults (9,367,000) needed OUD treatment. Among these, 55% (5,167,000) received OUD treatment, and 25% (2,353,000) received medications for OUD. Source - Treatment for Opioid Use Disorder: Population Estimates—United States, 2022 Morbidity and Mortality Weekly Report.

People in urgent need of treatment are often unaware of their treatment options, have limited access to treatment and counseling, or simply do not seek it out because they are afraid of being stigmatized. In addition, access is also limited by numerous legal restrictions for pharmacological treatment, inadequate training of clinicians, and the number of HCPs who are willing to treat this population.

During 2023, our INSUPPORT® Community Reentry Program (“CRP”) reached a celebrated milestone of receiving over 100 program enrollments. INSUPPORT was created to provide information aimed at helping eligible patients with the process of obtaining Indivior medicines and to enhance our existing patient transition of care offerings. CRP was designed for patients released from the CJS who are experiencing a gap in insurance coverage. Eligible patients may receive up to two months of SUBLOCADE® (buprenorphine extended-release) subcutaneous injection at no cost while awaiting reinstatement of health insurance.

Focus on the Criminal Justice System

In the U.S., a substantial share of persons suffering from OUD repeatedly cycle through the criminal justice system. Further, persons exiting the criminal justice system have been shown to be 40 times more likely to suffer from opioid overdose than persons in the general population.

While as recently as 2019 buprenorphine was rarely available to patients in criminal justice settings, such treatment is increasingly becoming available. The shift has been spurred by research findings and pronouncements from industry and professional medical societies that evidence-based treatment for OUD in correctional settings saves lives, which in turn has shaped changes in law and policy. Treatment for OUD in correctional settings has been shown to reduce overdose deaths by 75%, reduce recidivism by 32%, and reduce transmission of HIV and hepatitis.

Public policy is trending toward increasing treatment of SUD and serious mental illness in criminal justice settings. Congress continues considering legislation authorizing Medicaid coverage of persons in correctional settings. The Centers for Medicare & Medicaid Services (CMS) has published guidance to states on how they can apply to the agency for Medicaid funding to support treatment of patients with OUD and mental illness in the criminal justice system up to 90 days pre-release.

The U.S. Department of Justice (DOJ) issued guidance in April 2022 underscoring the rights of persons with OUD to treatment under the Americans with Disabilities Act, including in correctional settings. States have been increasingly enacting legislation and appropriations, and seeking federal waiver authority, to expand treatment availability in criminal justice settings.

Opioid Overdose Reversal

In addition to OUD treatments, we provide OPVEE (nalmefene) nasal spray for overdose reversal. A large and growing addressable market for opioid overdose reversal agents exists in the U.S., such as first responders, including fire departments, emergency medical services, law enforcement, and other community groups. We expect the primary customers for OPVEE to include state health departments, substance abuse centers, federal agencies, and eventually consumers through pharmacies fulfilling physician-directed or standing order prescriptions. The co-prescribing of opioid overdose reversal agents alongside prescription opioids has also driven growth of overdose reversal agents.