Titan’s Probuphine Dosing May Need Review, FDA Staff Says

Titan Pharmaceuticals Inc. plunged the most in four years after U.S. regulators questioned whether the company showed the dosages tested of experimental Probuphine implant offered enough benefit to gain approval.

The shares of South San Francisco, California-based Titan fell 42 percent to $1.19 at 4 p.m. New York time for their biggest drop since December 2008. Patient response to the treatment, for treating addiction to heroin and prescription opioid painkillers, indicate that doses may not have been “high enough” in the studies, Food and Drug Administration staff said today in a report.

The FDA staff also raised questions about the safety of the procedure to implant Probuphine and whether physicians who treat addiction yet don’t have surgical backgrounds would be capable of the operation. An advisory panel to the FDA is scheduled to meet March 21 to weigh the risks and benefits of the drug. The agency may decide by April 30 whether to approve the treatment.

“While the placebo group had even more discouraging results, supporting the conclusion that Probuphine does have an effect on drug use, overall, the response was not what one might hope for, given that the product ensures compliance with medication for six months,” FDA staff said in the report.

Urine Samples

After four months on the treatment, three patients had fully stopped using opioids. About a quarter of patients treated with the medication were unable to provide even four opioid-negative urine samples over the course of six months in clinical trials, according to the report.

The buprenorphine dose in four Probuphine implants is less than a third of the dosage delivered by 16 milligram buprenorphine film.

Addicts now can use Reckitt Benckiser Group Plc’s Suboxone tablets and dissolvable film that combine the same ingredient in Probuphine, buprenorphine, with naloxone to reverse the effects of overdose. If approved, Probuphine may generate $360 million in sales in 2018, Michael Higgins, an analyst for Brinson Patrick Securities Corp. in New York, said in an e-mail.

Probuphine is intended to deliver a long-lasting dose of buprenorphine, making it more convenient than daily oral versions. Buprenorphine is less restricted than other treatments for opioid dependence, such as methadone, which can only be administered in specialized clinics, according to the Substance Abuse and Mental Health Services Administration.

Matchstick-Sized Implant

FDA staff questioned whether a one-time training program for physicians to implant the matchstick-sized implant would be adequate to avoid potential complications ranging from pain and numbness at the infection sight to bleeding or hematoma and nerve damage.

Buprenorphine-related emergency room visits increased from 3,161 in 2005 to 30,135 in 2010, the agency said. Of the 2010 visits, 52 percent were classified as nonmedical use of pharmaceuticals versus 24 percent seeking substance abuse treatment and 13 percent for adverse reactions.

Probuphine has the potential to ensure treatment compliance and offer a decreased diversion or accidental abuse risk, Marc Rubin, chairman of Titan, said yesterday in an earnings call.

Titan licensed exclusive U.S. and Canadian commercialization rights for Probuphine to closely held Braeburn Pharmaceuticals, a New York-based Apple Tree Partners company. Titan has the potential to receive a $50 million milestone payment if the drug is approved.

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