FDA Approves Once-Monthly Buprenorphine Injection for Opioid Use Disorder
The FDA Commissioner noted the importance of providing an array of treatment options for opioid use disorder.
In a press release issued November 30, 2017, the US Food and Drug Administration (FDA) announced it has approved Sublocade, a once-monthly buprenorphine injection for moderate to severe opioid use disorder (OUD).1
Current buprenorphine-based treatments for OUD employ an oral mode of administration (in the form of a dissolvable film or tablets) and require daily intake, thus posing the issue of medication adherence. These treatments are also available in the form of an implant (Probuphine), which provides stable delivery of low-dose buprenorphine over a 6-month period.2 The agency's commissioner, Scott Gottlieb, MD, noted in the press release the importance of providing an array of treatment options for OUD. "Everyone who seeks treatment for opioid use disorder deserves the opportunity to be offered the treatment best suited to the needs of each individual patient, in combination with counseling and psychosocial support, as part of a comprehensive recovery plan," he said.1
Also in the press release, the FDA emphasizes that providing "the full range of medication-assisted treatments" is one of its focuses, and is in line with the US Department of Health and Human Services' first point in their "Five-Point Strategy to Combat the Opioid Crisis."3
Sublocade (RBP-6000) allows the sustained delivery of buprenorphine over a 1-month period, thanks to the Atrigel Delivery System, which, on subcutaneous injection, forms a solid deposit, subsequently broken down to steadily release the drug. The treatment is meant to be delivered in the form of a prefilled syringe by a clinician, and should be included in a comprehensive biopsychosocial treatment program.
In a study investigating the efficacy of RBP-6000 in subjects with moderate to severe OUD, initiated on a buprenorphine/naloxone sublingual treatment before receiving 2 RBP-6000 injections on days 1 and 29, the treatment was found to reduce "drug-liking" and reinforcing behaviors on challenges with the μ-opioid agonist hydromorphone (administered before and after RBP-6000 injections on 3 consecutive days of each week of the study period at 6 and 18 mg, and compared with placebo).4 The clinical development of RBP-6000 included a phase 1 study (ClinicalTrials.gov identifier: NCT03002961), evaluating a single-ascending dose of the drug, and a phase 2 multiple dose study (ClinicalTrials.gov identifier: NCT01738503), which demonstrated the safety and tolerability of the treatment for patients ages 17 to 65 years. A population/pharmacodynamic model indicated that "200 mg RBP-6000 dose should achieve 2–3 ng/mL buprenorphine average concentrations and desired efficacy."5 Clinical studies showed that patients treated with Sublocade had fewer weeks with positive urine tests and self-reported opioid use vs patients receiving placebo.
Treatment side effects include constipation, vomiting, nausea, and drowsiness. Postmarketing studies will assess the necessity of the pretreatment stabilization regimen with sublingual buprenorphine, the benefits of higher doses of Sublocade in patient subpopulations, and the efficacy of longer interdose intervals.
"We'll continue to pursue efforts to promote more widespread use of existing, safe and effective FDA-approved therapies to treat addiction," concluded Dr Gottlieb in the press release.
- FDA News Release. FDA approves first once-monthly buprenorphine injection, a medication-assisted treatment option for opioid use disorder. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm587312.htm. November 30, 2017. Accessed December 1, 2017.
- FDA News Release. FDA approves first buprenorphine implant for treatment of opioid dependence. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm503719.htm. May 26, 2016. Accessed December 1, 2017.
- US Department of Health and Human Services. Opioids: the prescription drug & heroin overdose epidemic. https://www.hhs.gov/opioids/index.html. Accessed December 1, 2017.
- Nasser AF, Greenwald MK, Vince B, et al. Sustained-release buprenorphine (RBP-6000) blocks the effects of opioid challenge with hydromorphone in subjects with opioid use disorder. J Clin Psychopharmacol. 2016;36(1):18-26.
- Nasser AF, Heidbreder C, Gomeni R, et al. A population pharmacokinetics and pharmacodynamic modelling approach to support the clinical development of RBP-6000, a new, subcutaneously injectable, long-acting, sustained-release formulation of buprenorphine, for the treatment of opioid dependence. Clin Pharmacokinet. 2014;53:813-824.