An FDA advisory committee has voted 12 to 5 to recommend approval of a buprenorphine implant (Probuphine) to treat patients who are already stable on low doses of the sublingual version of the drug.

The favorable vote followed a substantial re-analysis of clinical trial data by FDA reviewers, who raised concerns about missing data and the company's definition of a responder.

Ultimately, those re-analyses quashed drugmaker Braeburn Pharmaceuticals' suggestions that Probuphine was superior to sublingual buprenorphine, showing in conservative estimates that the company could only prove non-inferiority.

But for the panel majority, that was evidently enough to merit a recommendation to approve the product.

While the company's response rates were 96% for Probuphine versus 88% for sublingual buprenorphine, reviews by Rachel Skeete, MD, an FDA clinical reviewer, and James Travis, PhD, a statistics reviewer, found those figures were closer to 69% versus 64%.

An earlier attempt by Braeburn and another firm to win approval for the drug failed in 2013, with the FDA calling for new clinical efficacy data.

At issue in the Tuesday meeting was the company's exclusion of three patients -- two who were lost to follow-up and one who was incarcerated -- and not counting missing urine screening data as positive drug screens.

"The sponsor's analysis was incomplete, but the FDA's analysis was thorough," said panelist James Troendle, PhD, of the National Heart, Lung, and Blood Institute. "They used conservative assumptions that led to [the drug] still being able to pass a small non-inferiority margin, so I was convinced by that."

Several panelists noted that the drug's label, however, must be clear about patient selection for the medication, since the product is only intended for patients who have been stabilized on 8 mg daily buprenorphine or less.

Several of those who voted against approval said they did so based on the initial data rather than the FDA's re-analysis.

Margaret Kotz, DO, of Case Western Reserve University, noted that it's still not clear how to treat these patients after 2 years. The implants are expected to last only 6 months.

Judith Kramer, MD, of Duke University, who voted against approval, raised concerns that approval of the device was being conflated with the overarching opioid addiction problem in the country. She noted that a bigger barrier to medication-assisted treatment in the U.S. are the regulations that physicians can only treat a certain number of patients with buprenorphine.

"I don't think that with our desire to do something we should be careless about how we address" this problem, Kramer said.

She added that she was "very conflicted about this ... I was dismayed by what I thought was not a very rigorous approach on the part of the sponsor, in terms of things like leaving out three patients and claiming it's superior and repeatedly using that as the line. I felt there was already inflation going on here."

One panelist who voted in favor of approval said he was concerned about possible "aberrant use of this medication" if the population is not well defined.

"I worry we may incite harm with this implantable device," said Adam Gordon, MD, of the University of Pittsburgh. "Based on the evidence presented today, I voted yes -- not on the possible implications down the road."

The FDA is not obliged to follow advisory committee recommendations, but it usually does.