SILVER SPRING, MD. – Two Food and Drug Administration advisory panels have recommended approval of two new drug applications (NDA) for buprenorphine subcutaneous injections for the treatment of opioid dependence.
On Nov. 1, panelists recommended approval of some of the doses proposed in the NDA submitted by Braeburn Pharmaceuticals at the joint meeting of the Psychopharmacologic Drugs Advisory and the Drug Safety and Risk Management committees. The formulation, currently known as CAM2038, is intended to be used as part of a treatment plan that can include counseling and psychosocial support. The subcutaneous depot is available weekly, in 8-, 16-, 24-, and 32-mg injections, and monthly, in 64-, 96-, 128-, and 160-mg injections.
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On the previous day, Oct. 31, the panelists voted 18-1 with no abstentions to recommend an NDA submitted by Indivior. This formulation is known as RBP-6000.
Both formulations must be administered by a health care provider using a prefilled syringe with a predetermined dosage. The injection forms a biodegradable subcutaneous depot that, as it degrades, releases buprenorphine at a steady and controlled pace over the course of treatment – increasing the success of treatment for opioid use disorder.
Braeburn’s NDA was based on results of a double-blind, randomized, within-subject, inpatient laboratory study of 47 patients over 14 days. Patients were randomized into two groups: 22 patients in the 24-mg group and 25 patients in the 32-mg group. Patients were administered an initial dose on day 0 and a follow-up dose on day 7. The results of the study found a complete blockade of opioids after the first injection that was sustained over the 1-week interdosing interval.
The committees said that of most of the doses should be approved, but a majority of committee members were uncomfortable with the higher doses.
Voting on Indivior’s NDA was based, in part, on the results of a randomized, double-blind, placebo-controlled, multicenter phase 3 study. The study lasted 24 weeks and randomly assigned 504 patients into one of three groups based on monthly dosing regimen of buprenorphine: 300 mg/300 mg, 300 mg/100 mg, and placebo. After randomization, the 300 mg/300 mg group had 201 patients, the 300 mg/100 mg group had 203 patients, and the placebo group had 100 patients. The study found that the primary and secondary endpoints were met, and significantly higher percentage of abstinence with subcutaneous buprenorphine were observed. Patients in both the 300 mg/300 mg and 300 mg/100 mg groups had very similar distributions of percentage of weeks patients abstained from opioid use with more than 20% of patients achieving 80%-100% abstinence from opioids during the course of the study, a significant improvement over the placebo group.
The panels’ recommendations come against the backdrop of the opioid epidemic in the United States, which President Trump has deemed a public health emergency. Many of the panel members and speakers at both meetings expressed support for the NDAs in that context and emphasized that, unlike sublingual administration of buprenorphine, these treatments do not require daily intervention. In addition, sublingual tablets are easier to abuse or more likely to lead to overdose because the patient must self-administer the medication. Expanding the toolkit of physicians who treat opioid use disorder might help stem the tide of the epidemic, some speakers said.
Usually, the FDA follows its advisory panels’ recommendations, which are not binding.