A private-practice addiction specialist who has held the federal waiver for prescribing buprenorphine products for more than a decade believes the most recently approved formulation of the medication to treat opioid dependence could represent a significant breakthrough for treatment. Yet as a buprenorphine and naloxone product that will dissolve inside a patient's cheek is readied for a fall launch to market, this physician also acknowledges that further advances in administration may not be far off as well.
“A depot injection has been in development, and a nasal spray has been in the pipeline,” says Richard Soper, MD, a Nashville, Tenn.-based prescribing physician whose addiction-focused practice is the Center for Behavioral Wellness. He attributes the intense interest in developing alternate routes of administration for buprenorphine and buprenorphine-naloxone to numerous factors, from the basic economics associated with surging opioid use to a gradual shift in public attitudes about opioid addiction and addicts.
“Socio-culturally we're sort of getting close to the time similar to when the former secretary of transportation Drew Lewis came forward publicly as an alcoholic, just before Betty Ford did, and a paradigm shift began,” says Soper. “We're starting to educate our general public that this is no character defect.”
North Carolina-based pharmaceutical company BioDelivery Sciences International, Inc., announced this month that it had received approval from the Food and Drug Administration (FDA) to market the trademarked BUNAVAIL buccal film for maintenance treatment of opioid dependence. The buprenorphine-naloxone combination product, which like other buprenorphine products is designed for use in conjunction with psychosocial counseling, is expected to hit the market late in the third quarter of this year.
The company reported that in a 12-week Phase 3 clinical study of 249 patients who were converted from sublingual tablet or film forms of buprenorphine-naloxone (Suboxone) to BUNAVAIL, patients stayed in treatment at a high rate and had few positive urine tests for non-prescribed opioids. In addition, more than two-thirds of patients who had experienced constipation during Suboxone treatment said these symptoms resolved after they switched to BUNAVAIL.
BUNAVAIL will be packaged in individually wrapped, thumbnail-size squares, with an inert component surrounding the actual medication. A patient will place the square on a finger and push it onto the inside of his/her cheek, where it will attach after a few seconds and then dissolve within 10 minutes. Soper emphasized the ease of the delivery system in that it should not interrupt a patient's work or other activities.
“It's absorbed significantly better than Suboxone,” says Soper. “I think this potentially will have an impact in the marketplace.”
According to Al Medwar, BioDelivery Sciences' vice president of marketing and corporate development, patients in the Phase 3 study took BUNAVAIL once a day, at a mean final dose of 8 mg. These patients' mean final daily dose of Suboxone before conversion had been around 16 mg, says Medwar.
The manufacturer announced this month that it expects up to $250 million in U.S. sales potential for its medication. Company president and CEO Mark A. Sirgo said in a news release, “This is also a transformative event for [the company], as we will be launching a product with our own dedicated sales force for the first time...”
Approval of BUNAVAIL represents the latest development in a fast-changing drug marketplace around buprenorphine products since Reckitt Benckiser's Suboxone was approved and transformed practice in treating opioid addiction, allowing for better management of patients' condition within a physician office setting.
Reckitt Benckiser transitioned from sublingual Suboxone tablets to the more easily absorbed sublingual Suboxone film as the patent protection on the former approached expiration. Since then, generic versions of buprenorphine-naloxone tablets have reached the market; a smaller-dose combination product Zubsolv was introduced by a competing manufacturer; and Purdue Pharma received approval for a buprenorphine-only transdermal patch indicated for pain management.
Topics that have swirled around this active market include the question of buprenorphine-naloxone combination products' diversion/abuse potential (Soper says there clearly has been some diversion, even though the products originally were marketed as being risk-free in this area), and the issue of when use of buprenorphine without naloxone is warranted (pregnant women are among those for whom buprenorphine without naloxone represents the preferred option).
Soper says of diversion, “We know that goes on, but what we need to look at deeper, at the core, is what is the brain chemistry of this disorder, and how do we help people who are dealing with this disorder, in building their life skills.”
He adds in regard to the newest formulation of buprenorphine-naloxone, “I haven't figured out yet how this can be abused.”