Washington Editor

Titan Pharmaceuticals Inc. is a step closer to filing a new drug application (NDA) for its Probuphine as a weapon to fight opioid dependence.

Topline results reported Monday showed the subcutaneous implant formulation of buprenorphine met the primary endpoint of a Phase III confirmatory trial. It also demonstrated noninferiority to Suboxone (buprenorphine/naloxone), a sublingual formulation and current gold standard for treating opioid addiction.

The South San Francisco-based Titan expects to have full results from the study by early August. After meeting with the FDA this fall, the company plans to file its NDA early next year, Katherine Beebe, Titan's executive vice president and chief development officer, told BioWorld Today.

The topline results confirmed the efficacy of Probuphine compared with placebo on the primary endpoint based on the percentages of urine samples tested negative for illicit opioid use over the 24-week treatment period. The urine samples supported results from patient self-reports of opioid use.

The Phase III trial was a randomized, placebo- and active-controlled study conducted at 20 sites in the U.S. that treated 287 patients, ages 18 to 60, across three dosing arms: Probuphine (114 patients), Suboxone (119 patients) and placebo implants (54 patients). The Probuphine and placebo dosing arms were double-blinded while the Suboxone arm was open-label.

In 2009, sales of Suboxone in the U.S. drove Berkshire, UK-based Reckitt Benckiser's prescription drug business up by more than 50 percent. The U.S. Suboxone business brought in £502 million (US$794 million) with an adjusted operating profit of £345 million. (See BioWorld Today, Jan. 4, 2011.)

While buprenorphine has proven useful in treating opioid addiction, it is itself an opioid and can be subject to abuse and misuse, especially in a sublingual tablet or film form, Beebe said.

Titan's Probuphine is implanted in the upper arm in a five- to 10-minute procedure in a doctor's office and then removed six months later. If needed, a new implant can be placed in the other arm at that time.

If the drug is approved, it would be subject to a classwide risk evaluation and mitigation strategy for extended-release and long-acting opioids, which the FDA expects to become effective next year. (See BioWorld Today, April 21, 2011.)

Meanwhile, Titan is already looking down the pipeline. Because of its ability to deliver buprenorphine six months or longer while maintaining steady blood levels, Probuphine could hold promise as a treatment for chronic pain, Titan President Sunil Bhonsle told BioWorld Today.

The company also is looking at the potential of using its implant technology to deliver drugs in areas such as Parkinson's, where long-term delivery is needed, he said.