|Buprenorphine (orange) binds to the mu opioid receptors in the brain to block opioids from attaching to them. Titan hopes to commercialize the implant to deliver the drug, which is currently available in sublingual tablet and oral formulations.--Courtesy of Titan Pharmaceuticals|
Titan Pharmaceuticals ($TTNP) said yesterday that the Phase III study of its Probuphine subdermal implant for the treatment of opioid dependence is now halfway to full enrollment and on track to conclude by mid-2015, giving the company a second crack at FDA approval.
All 21 sites are recruiting patients, with 94 enrolled so far out of about 180 needed, the company said in a release. The trial is not only double-blind but double-dummy, meaning patients on the Probuphine implant will receive daily sublingual pills, and those taking sublingual buprenorphine pills will receive four placebo implants (thus all patients receive a dummy and placebo form of therapy).
The primary endpoint will be a noninferiority comparison of the patients in the two arms, Titan said in the release. The company wants to leave no room for doubt after the FDA overrode its advisory panel's recommendation and rejected the implant in 2013 citing uncertainty about its efficacy and "human factors testing of the training associated with Probuphine's insertion and removal."
"The current trial was designed to address the FDA's main concern that the Probuphine dose used in the earlier studies was too low for the kind of patients who were being tested, and the clinical benefit would be greater in a different patient population. Specifically, the patients in the earlier studies were new to medication treatment, and required a 12-16mg/day dose of sublingual buprenorphine to achieve clinical control over withdrawal symptoms and opioid cravings. The patients in the current study are considered clinically stable by their treating physician and have received a maintenance dose of less than or equal to 8mg/day of sublingual buprenorphine for at least 3 months prior to randomization," wrote a Titan spokeswoman in an email to FierceMedicalDevices.
"We believe the pace of enrollment reflects the great need for new long-term maintenance treatment options for those suffering from opioid dependence. We look forward to working with our clinical investigators to complete this study expeditiously, and if ultimately approved by the FDA, the opportunity to provide physicians and their patients a unique treatment alternative," said Behshad Sheldon, CEO of Braeburn Pharmaceuticals, in a statement. Titan has granted Braeburn North American commercial rights to the product, meaning it is entitled to milestone payments and royalties from Braeburn on sales of the product upon approval.
The implant delivers buprenorphine, which is currently available in sublingual tablet and oral formulations--a market with 2012 annual sales of about $1.5 billion in the U.S., according to Titan. If approved, the product would be the "first and only commercialized treatment of opioid dependence to provide continuous, around-the-clock blood levels of buprenorphine for 6 months following a single procedure," Kate Glassman-Beebe, Titan's chief development officer, said in a prior statement.
The product uses Titan's ProNeura drug delivery system. "The continuous drug delivery system consists of a small, solid rod made from a mixture of ethylene-vinyl acetate and a drug substance," Titan explains on its website. It is typically placed subdermally in the upper arm and delivers buprenorphine for 6 months. The company says that the delivery system has shown promise as a treatment for Parkinson's disease in nonclinical studies.
- read the release
Editor's Note: This article has been updated to include additional information about the trial from Titan Pharmaceuticals.