The Food and Drug Administration wants Titan Pharmaceuticals (OTCC: TTNP) to conduct a new clinical study of its novel Probuphine implant, according to the minutes of a November meeting with the agency that the company released today.
The Probuphine implant gives patients a steady dose of buprenorphine, an opioid addiction treatment drug, for up to 6 months via tiny rods about the size of a matchstick, which are implanted under the skin in the upper arm. Currently, buprenorphine is only available in generic tablets and in film formulations sold under the brand name Suboxone.
In April, the FDA denied approval of the implant, asking for additional information on its effectiveness. Since then, Titan has been working with the agency to resolve any issues with the implant.
“The FDA emphasized its commitment to working with Titan and its partner, Braeburn Pharmaceuticals, to pursue a reasonable path to approval, and all parties agreed that seeking an indication in individuals stabilized on 8 mg/day or less of sublingual buprenorphine may be a suitable approval pathway for Probuphine,” the company said in a statement.
Such a study, according to the minutes of the meeting, “need not be large” and must be at least six months long. Titan said it was working with experts in the field to develop a new clinical study design for submission to the FDA within the next few weeks.
“We appreciate the FDA’s close consideration of our proposal addressing the CRL (complete response letter) and its continued support to advance the Probuphine program,” said Sunil Bhonsle, president of Titan Pharmaceuticals.
“While our path forward includes an additional clinical study, we are encouraged by the FDA’s noted willingness to work closely and iteratively with us on all aspects of the CRL to ensure a mutually feasible and expeditious path to approval.”
The company was caught off guard in April when the agency denied approval of the implant, because an FDA advisory committee had voted 10 to 4 a month earlier in favor of the effectiveness and safety of Probuphine.
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. The agency also 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.
Titan and other drug makers are anxious to enter the lucrative market for Suboxone. Sales of Suboxone/buprenorphine reached $1.5 billion in the U.S. in 2012 and are growing by about 10% annually. This year the FDA approved generic tablet versions of buprenorphine, 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.
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.
According to Titan, about 20% of the 2.2 million opioid addicts in the U.S. are addicted to illicit opioids such as heroin, and the other 80% to prescription painkillers such as oxycodone, hydrocodone, methadone, and codeine.