Titan Pharmaceuticals, Inc. (OTCC: TTNP) has announced that it received a letter from the Food and Drug Administration delaying approval for an implantable version of buprenorphine, an opioid addiction treatment drug more widely known as Suboxone.
Titan said the FDA cannot approve the application in its present form for the Probuphine implant and asked for additional information on its effectiveness.
“Titan and our partner, Braeburn Pharmaceuticals, are extremely surprised and disappointed with the FDA’s response,” said Marc Rubin, MD, executive chairman of Titan Pharmaceuticals.
“Given the nationally-recognized, growing and devastating opioid dependence epidemic, there is critical need for new safe and effective treatments that reduce the likelihood of abuse, diversion and accidental pediatric exposure, and Titan and Braeburn remain committed to making Probuphine available for patients that need it.”
In March an FDA advisory committee voted 10 to 4 in favor of the implant, with one abstention. The advisory committee also voted in favor of the effectiveness and safety of Probuphine. However, a majority of the committee members abstained on the vote pertaining to the drug’s Risk Evaluation and Mitigation Strategy (REMS) program.
The Probuphine implant gives patients a steady dose of buprenorphine for up to 6 months via four to five rods, each about the size of a matchstick, which are implanted under the skin in the upper arm. Currently, buprenorphine is only available in oral tablet and film formulations (Suboxone).
Titan claims Probuphine is safer and less likely to be abused then other forms of buprenorphine because the implant is placed by a physician and is not readily accessible to patients, reducing the potential for overdose, abuse and diversion.
But FDA staff questioned the effectiveness of the implant and suggested the dose was too low, noting in clinical trials that about half of the patients treated with Probuphine required additional doses of Suboxone to treat their withdrawal symptoms. FDA staff said Probuphine limits drug use but, “overall the experience was not what one might hope for.”
According to Titan, the FDA letter requested additional data on the implant’s effectiveness at higher doses, as well as information on training associated with the insertion and removal of the implants. The letter also included recommendations regarding product labeling and the implementation of the Risk Evaluation and Mitigation Strategy (REMS).
Titan has an exclusive license agreement with Braeburn Pharmaceuticals to the rights for Probuphine in the United States and Canada. Titan received an upfront payment of over $15 million from Braeburn and would receive up to $50 million if Probuphine is eventually approved by the FDA. In addition, Titan will also receive royalties on net sales of Probuphine and additional payments if the implant is approved for other uses, such as treating chronic pain.
Titan and other drug makers are anxious to enter the lucrative market for Suboxone. Sales of Suboxone reached $1.3 billion in the U.S. in 2011 and are growing by about 10% annually. Recently the FDA approved generic tablet versions of Suboxone, effectively ending a decade-long monopoly that a British Pharmaceutical company, Reckitt Benckiser, had on sales of the drug.
Buprenophine was first approved as a treatment for opioid addiction in the U.S. in 2002. Over three million Americans with opioid dependence have been treated with Suboxone. Although praised by addiction experts as a tool to wean addicts off opioids, some are fearful the drug is being overprescribed and misused, leading to even more addiction.