Weekly buprenorphine provides opioid blockade, withdrawal suppression

By Will Boggs MD

NEW YORK (Reuters Health) - Buprenorphine weekly depot (CAM2038) safely provided immediate and sustained opioid blockade and suppressed withdrawal in individuals with opioid use disorder, in a phase II study.

A surprising finding “was that individuals could be inducted directly (i.e., initiate treatment with buprenorphine) onto CAM2038 without requiring initial stabilization on sublingual buprenorphine,” Dr. Sharon L. Walsh from University of Kentucky in Lexington told Reuters Health by email. “This suggests that it can be used for in-office induction in the same way that physicians are already familiar with when starting sublingual buprenorphine; that is, have the patient refrain from using opioids for a period sufficient to produce some opioid withdrawal.”

Buprenorphine has been shown in numerous studies to reduce illicit opioid use, retain patients in treatment, and reduce mortality in patients with opioid use disorder. CAM2038 is a sustained-release subcutaneous buprenorphine formulation that releases the drug at a steady rate as the depot biodegrades over the course of one week.

Dr. Walsh and colleagues tested once-weekly CAM2038 24 mg and 32 mg (to mimic plasma concentrations within the range produced by sublingual buprenorphine 16 mg and 24 mg, respectively) in 47 inpatients with opioid use disorder.

Treatment with CAM2038 significantly suppressed responses to hydromorphone without significant "bad drug effect" ratings, they reported June 22nd online in JAMA Psychiatry.

Opioid withdrawal symptoms, which were modestly elevated at baseline, were completely suppressed on day 1 after CAM2038 and remained suppressed for the rest of the week.

There was no evidence that CAM2038 precipitated withdrawal in any of the participants.

CAM2038 also reversed the hydromorphone-induced reductions in oxygen saturation.

Most participants (64% with 24 mg and 96% with 32 mg) experienced one or more adverse events. Those thought to be related to CAM2038 included constipation (19%), injection-site pain and erythema (9% each), and headache (6%), with most rated as mild severity.

“The main message for physicians is that the number of options (with dose and dosing frequency flexibility) for providers and patients should increase hopefully soon,” Dr. Walsh said. “Long-acting formulations should give assurance to treating physicians that the patients are receiving the correct dose and that the risks of overdose, misuse, and diversion associated with large supplies of daily buprenorphine should be obviated with a depot formulation.”

“Opioid use disorder puts patients’ lives at high risk for death, and we have approved and effective treatments . . . that save lives,” she said. “We need to expand treatment and integrate addiction medicine services into all specialty areas in order to reach as many patients as possible. We also need to advocate for reducing the barriers to treatment and reducing stigma in order to expand our reach to patients in need.”

“The sponsor hopes to submit their NDA (new drug application) shortly to the FDA (and is simultaneously working with a partner, Camurus, for approval in Europe and Australia),” Dr. Walsh said. “The FDA granted fast track status and once the NDA is submitted, the FDA can grant priority review status, if they agree with the sponsor's justification. If this occurs, then the NDA’s action date could be first half of next year.”

Dr. Kelly Dunn from Johns Hopkins University School of Medicine, Baltimore, Maryland told Reuters Health by email, "CAM2038 appeared to function very similarly to the 16 and 24 mg doses of buprenorphine/naloxone (commonly referred to as Suboxone), but reduces many of the risks associated with sublingual buprenorphine prescribing for opioid use disorder treatment. Further, administration of an external opioid (hydromorphone) - which was meant to model relapse to opioid use - did not result in untoward physiological or positive drug effects in the majority of patients.”

“Overall, these results suggest that CAM2038 - at the doses administered here - appears to be both safe and effective for the treatment of OUD,” she said.

She added, “It will be important for policy-makers and insurance companies to embrace this new technology and provide prescribers with the financial and logistical support they need to be able to dispense this and other extended-release medications as widely as possible.”

Dr. Erin Kelty from The University of Western Australia, Crawley, told Reuters Health by email, "This preparation may be a useful product for the treatment of opioid use disorders, particularly for patients who cannot attend a pharmacy multiple times per week for treatment or are likely to divert. However, more research is required, particularly on the patient acceptance of the treatment and long-term treatment outcomes.”

“The study did not include the current registered buprenorphine preparation as a control group,” she said. “Thus, it is unclear how the exposure to extended release buprenorphine compares to sublingual preparation in terms of pharmacokinetic parameters such as AUC. There are no comparisons between adverse events, patient’s acceptance of the injection, or compliance with the current registered formulation.”

Furthermore, Dr. Kelty said, it’s not clear that one-week injections are a substantial advance. An existing depot form of intramuscular naltrexone approved for opioid use disorders lasts 28 days, she said, “and there are preparations in development that last significantly longer (>6 months).”

Study sponsors Braeburn Pharmaceuticals and Camurus employed three of the 12 authors and had various relationships with six other authors.

SOURCE: http://bit.ly/2tTs5NM

JAMA Psychiatry 2017.

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