This article is a Clarivate Analytics Market Insight report, an ongoing series featuring expert reviews of hot topics in the pharma/biotech field, with analysis and discussion on the factors currently affecting the industry. Data leveraged for this analysis was gathered from Clarivate Analytics Cortellis.
According to the latest National Survey on Drug Use and Health (NSDUH), in 2016, more than 11.5 million Americans had misused prescription opioids in the previous year and more than 2 million were addicted to prescription or illicit opioids.1 The Centers for Disease Control and Prevention (CDC) estimates that drug overdoses account for the death of 91 Americans per day and the current White House administration has declared the opioid crisis a public health emergency.2 For people wanting to overcome their opioid use, adherence to a medication-assisted treatment (MAT) program can reduce opioid withdrawal symptoms and cut risk of death by half.3-5 Three FDA-approved MAT options (methadone, buprenorphine and naltrexone) are available in various formulations and dosages, with daily oral buprenorphine the standard of care. The highly anticipated first once-monthly formulation of buprenorphine (Indivior’s Sublocade), approved in November 2017, could disrupt the market upon launch in early 2018. According to Cortellis Consensus Forecast data (source Thomson Reuters I/B/E/S), 2023 sales of $1.464 billion are anticipated for Sublocade, topping current market leader Suboxone.
The growing opioid problem
Before 1995, opioids were only prescribed for extreme pain, but in the late 1990s, healthcare providers in the U.S. began using opioids to treat chronic pain, such as arthritis and back pain, resulting in people taking opioids for longer periods of time or in higher doses thereby increasing the risk of addiction, overdose and death. Since then, opioid prescription has exploded; more than one third of Americans were prescribed opioids in 2015, according to a NSDUH report, and CDC figures show that the number of opioid-related overdose deaths has quadrupled since 1999.6-7
Actions taken to mitigate the opioid crisis
In light of the emergency, several measures have been introduced in recent years. For instance, new American Society of Addiction Medicine (ASAM) National Practice Guidelines, adopted in 2015, and CDC clinical practice guidelines for prescribing opioids for chronic pain, issued in 2016, are improving standards of care. The Comprehensive Addiction and Recovery Act (CARA) was signed into law in July 2016 and the 21st Century Cures Act (Cures Act) was enacted by Congress in December 2016, underscoring federal recognition of the problem. Also in 2016, the FDA announced plans to overhaul its regulation of opioids, such as enhancing safety labeling, driving use of tamper-resistant/abuse-deterrent opioids and re-examining the risk-benefit paradigm for their use. Resultant FDA action has included a request for voluntary market withdrawal of Endo Pharmaceuticals’ Opana ER, which was withdrawn in July 2017.
Governed by federal legislation and guidelines, and a focus of the FDA’s ongoing work to reduce the scope of the opioid crisis, is the improvement of access to prevention, treatment and recovery services. MAT which uses approved medications along with counseling and behavioral therapies to treat opioid use and prevent overdose has been shown to help enable people to regain control of their lives. Three drugs are FDA-approved for the treatment of opioid addiction (the partial opioid agonist buprenorphine, the full opioid agonist methadone and the opioid antagonist naltrexone), and all are available in different formulations and dosing schedules. However, patients, physicians, policymakers and other stakeholders have expressed the need for additional treatment options, and the FDA now actively encourages the development of new forms of MAT and better formulations of existing drugs.
Sublocade, the first once-monthly buprenorphine product
The FDA approved Indivior’s Sublocade in late November 2017, making it the first once-monthly buprenorphine product for the treatment of opioid use disorder. Sublocade is a drug-device combination product that uses buprenorphine and the Atrigel Delivery System in a pre-filled syringe. It is administered subcutaneously to patients who have initiated treatment with a transmucosal buprenorphine-containing product and who have been on a stable dose of buprenorphine for a minimum of seven days.
Sublocade, at steady state, delivers buprenorphine at a sustained rate of at least 2 ng/ml over a one-month period, translating to mu-opioid receptor occupancy >/=70%, and achieved complete blockade of drug-liking effects for a full month in most patients in the phase II Opioid Blockade study. In a phase III trial, Sublocade demonstrated significantly higher abstinence rates compared with placebo (42.7% versus 5.0%) and outperformed placebo in both opioid presence in urine samples and self-reported opioid use. Significantly more Sublocade-treated patients completed the six-month study than placebo (64.3% versus 33.3%), and the placebo group experienced an increase in withdrawal symptoms and opioid craving versus baseline despite more than twice the rate of illicit opiate use in placebo patients as early as week 2.
The MAT therapy market and Sublocade’s role
When Sublocade enters the U.S. market early this year, it will be a welcome addition to current options. Daily oral methadone had been standard of care for outpatient treatment of opioid addiction for more than 30 years, while the current standard of care is daily oral buprenorphine. Indivior’s Suboxone, an abuse-deterrent formulation of buprenorphine in sublingual film or tablet formulation that releases the opioid antagonist naloxone if crushed for injection, has been available in the U.S. since 2003 and is the current market leader. Newer daily, oral buprenorphine formulations have been launched, such as Orexo’s Zubsolv in September 2013 and BioDelivery Sciences’s Bunavail in November 2014, both of which are also buprenorphine plus naloxone combinations. Zubsolv is a sublingual tablet formulation and Bunavail a buccal high-dose formulation, and both have improved bioavailability versus Suboxone. The first six-month subcutaneous sustained-release implant of buprenorphine entered the market in June 2016 in the form of Braeburn Pharmaceuticals/Titan’s Probuphine. In addition to methadone and buprenorphine, the third FDA-approved opioid addiction treatment is naltrexone, and in October 2010, Alkermes’s Vivitrol became the first once-monthly, non-addictive treatment for the prevention of relapse to opioid dependence following detoxification.
There are a few issues with the current MAT options, such as the burden and inconvenience of the daily oral buprenorphine or methadone treatments, which can contribute to low compliance and suboptimal outcomes, increasing the risk of relapse. Also being dispensed to patients for self-administration makes those treatments susceptible to diversion. The buprenorphine implant is placed with a minor in-office surgery, thereby introducing risks associated with surgical procedures such as infection, scarring and nerve damage. And although Vivitrol has the advantage of being once-monthly and non-narcotic, it requires a detox period before patients can receive their first injection, which can prove problematic for addicted patients.
The approval of the first long-acting buprenorphine Sublocade addresses limitations of current treatments by replacing daily oral medications with an injectable, once-monthly medication to be administered by a healthcare provider, thereby enhancing compliance and clinical outcomes, improving quality of life and making abuse and diversion difficult. Sublocade has a safety profile consistent with the safety profile of transmucosal buprenorphine, except for injection-site reactions (seen in 16.5% of patients) and like the others, is a Schedule III controlled substance that is only available through a REMS program in conjunction with a complete MAT program. Additionally, with no need for detoxification and the same monthly dosing profile, Sublocade diminishes one of the biggest competitive advantages of Vivitrol.
While market leader Suboxone achieved peak sales of $1.082 billion in 2013, sales are now in decline and are forecast at $232.0 million in 2021, having been buffeted by generic competition and direct competitors. Sales of Sublocade, however, are forecast to reach blockbuster status in 2022 at $1.072 billion, thereafter increasing further and topping Suboxone peak sales. Noteworthy among the other MAT options, Vivitrol forecasts for 2023 are $826.0 million, following an upward trajectory, and the peak market potential for Zubsolv is estimated at $500.0 million.
The U.S. market is also likely to see further new entries in the near term such as Braeburn’s CAM-2038, another subcutaneous buprenorphine formulation for potential weekly and monthly injection. An NDA filing has been accepted and a decision is expected early in 2018. If approved, CAM-2038 will have an advantage over Sublocade; while Sublocade requires initiating treatment with an oral buprenorphine product for at least seven days until dose stabilization, CAM-2038 will not have this requirement.
MAT impact and summary
The misuse of opioids has become one of America’s biggest public health challenges. Regular adherence to a MAT program is one option for treating opioid use disorders although there are many obstacles to accessing quality treatment and achieving treatment success. The main criticism of MAT is that it merely replaces one drug with another, but educating healthcare providers, payors, governments, policy makers, stakeholders and patients about the disease and clinically proven treatment methods is of significant value in the ongoing fight in the opioid crisis. Adhering to a treatment plan that includes daily treatment can be challenging for addicted patients, but there is great hope that the addition of once-monthly buprenorphine as an MAT option will provide more choice for patients and have the potential to greatly influence the way patients are treated by freeing them from the daily decision and reminder of the disease. While the MAT market is lucrative, the amount paid for treatment only represents a small portion of the costs these disorders impose on society, making Sublocade, and other MAT options that are available or may follow, important contributors in combating the opioid epidemic.
The Incidence and Prevalence Database from Clarivate Analytics includes full multi-citation summaries for opioid dependence, addiction, and abuse (ICD 304.0), as well as more than 4,000 other diseases and procedures. Learn more.