FDA Drops the Hammer on Titan: CRL for Probuphine
By Marie Powers
In an understatement, Titan Pharmaceuticals Inc. said it was “extremely surprised and disappointed” to receive a complete response letter (CRL) from the FDA for Probuphine, the company’s investigational subdermal implant for the maintenance treatment of opioid dependence in adults.
Titan investors were active over the past two days, moving the company’s shares (NASDAQ:TTNP) up and down in roughly a 15 percent trading range while awaiting word from the FDA. When that word came, the stock swooned, dipping Wednesday morning from Tuesday’s closing price of $1.66 to a 52-week low of 32 cents, an 80 percent drop.
The South San Francisco-based company said the FDA issued the CRL Tuesday evening, requesting additional data on the ability of Probuphine to provide opioid blockade of relevant doses of agonists, the effect of higher doses of Probuphine that approximate blood plasma levels associated with 12 mg to 16 mg sublingual doses of buprenorphine per day and the human factors testing of physician training associated with Probuphine’s insertion and removal.
Marc Rubin, Titan’s executive chairman, said the company and its partner, Braeburn Pharmaceuticals, “remain committed to making Probuphine available for patients that need it.”
Probuphine uses Titan’s ProNeura technology to deliver six months of buprenorphine hydrochloride following a single treatment. The implant is designed to deliver buprenorphine in a maintenance formulation with less abuse potential than currently marketed forms of the drug, such as Suboxone (buprenorphine/naloxone, Reckitt Benckiser Pharmaceuticals Inc.).
The new drug application for Probuphine was filed through the 505(b)(2) pathway. The clinical development program was capped by a randomized, placebo- and active-controlled Phase III confirmatory study that enrolled 287 adults at 20 U.S. sites 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.
Findings confirmed the efficacy of Probuphine compared with placebo on the primary endpoint: 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. (See BioWorld Today, June 11, 2011.)
See Thursday's BioWorld Today for More on This Story.
Suite: 1100 | Atlanta, Georgia 30346, USA
In the U.S. and Canada: 1-800-477-6307
Outside the U.S.: 1-770-810-3144
In the U.S. and Canada: 1-800-336-4474
Outside the U.S.: 1-215-386-0100
Hours: Monday - Friday, 8:00am - 6:00 pm EST
Sign up for Highlights FREE e-mail newsletter