In the end, a vote by an outside panel of FDA experts favoring approval of Titan Pharmaceuticals' Probuphine didn't influence the outcome at all. Agency staffers stuck with the opinions outlined in a harsh internal review and rejected the opioid addiction drug, outlining some extensive demands for new clinical data that would be needed for an approval.
The news was a disaster on Wall Street. Investors bailed on the sudden reversal of fortune, driving the stock down 80% and leaving Titan as a penny stock as it faces a tough period.
In a statement, Titan ($TTNP) outlined three key requirements on new efficacy data. Titan will have to offer clear evidence of:
- The ability of Probuphine to provide opioid blockade of relevant doses of agonists.
- The effect of higher doses of Probuphine, ideally doses more closely approximating the blood plasma levels associated with sublingual doses of buprenorphine of 12 to 16 mg/day.
- Human factors testing of the training associated with Probuphine's insertion and removal.
The FDA's panel had voted 10 to four in favor of an approval, but the agency had no problem overlooking the majority support along with Titan's claim that Phase III data demonstrated that Probuphine, an implant that releases buprenorphine over a period of 6 months, was better than a placebo at preventing addicts from using illicit opioids. Investigators also said it was noninferior to the approved therapy. But staffers picked apart that argument in the internal review.
"Even after allowing four months for engagement in treatment, only three Probuphine-treated patients were fully abstinent from opioids," noted the staff. "Approximately 8% provided negative samples for at least 80% of tests."
"Titan and our partner, Braeburn Pharmaceuticals, are extremely surprised and disappointed with the FDA's response," said Dr. Marc Rubin, executive chairman of Titan Pharmaceuticals. "Probuphine is a diversion-resistant formulation that is consistent with the recently-issued FDA guidance supporting diversion- and abuse-resistant products, and the NDA was designated Priority Review by the FDA. We believe Probuphine has demonstrated both safety and efficacy in accordance with primary endpoints that were pre-agreed with the FDA and, moreover, the safety, efficacy and overall approval of Probuphine was strongly supported by the Psychopharmacologic Drugs Advisory Committee."
Titan says it plans to meet with the FDA before it lays out a plan for next steps.
- here's the release