Titan Pharmaceuticals Confirms Meeting With U.S. FDA

SOUTH SAN FRANCISCO, CA--(Marketwire - August 31, 2011) -

Titan Pharmaceuticals, Inc. (OTCBB: TTNP) today announced that the U.S. Food and Drug Administration (FDA) has confirmed an October 25, 2011 Pre-New Drug Application (Pre-NDA) meeting with Titan regarding Probuphine™. Probuphine is an innovative, subcutaneous implant formulation that delivers a steady, round-the-clock dose of the marketed drug buprenorphine over six months following a single treatment and is being developed by Titan for the treatment of opioid dependence. Titan recently announced positive Phase 3 confirmatory trial results for Probuphine.

At the upcoming meeting, Titan will review all elements of its Probuphine development program and seek FDA input and guidance on the proposed content of a New Drug Application (NDA). In preparation for the meeting, Titan is required to submit to the FDA a comprehensive briefing document by mid-September that includes data from all the non-clinical and clinical studies and the chemistry, manufacturing and control processes and procedures for the manufacturing of Probuphine.

The FDA has agreed that the Probuphine NDA submission will be reviewed under its 505(b)(2) regulations and can reference data that are in the public domain as well as rely on the FDA’s prior review of safety or efficacy for the reference listed drug. The briefing document, to be submitted in mid-September to the FDA, will include information on the following:

• Two placebo controlled Phase 3 studies, both of which met the primary efficacy endpoints of Probuphine compared to placebo in the treatment of opioid dependence.

• Safety information on Probuphine from several non-clinical studies, as well as six clinical studies that have enrolled a total of 618 patients. Probuphine was well tolerated in these studies with the majority of adverse events being mild to moderate in severity and unrelated to the study treatment. The safety database includes information from the following:

  • 499 patients undergoing implant insertion and removal procedures (either Probuphine or placebo)
  • 283 patients treated with Probuphine in planned six-month studies, with 70% completing the full six months and 82% completing at least four months
  • 107 patients treated with Probuphine in retreatment studies (one of which is currently ongoing and expected to be completed by the end of this year), with 68% completing the full 12 months and 83% completing at least 10 months to date
  • Relative bioavailability and pharmacokinetics of Probuphine compared to Suboxone®
  • Comparative safety information on Probuphine and Suboxone treatments

• Manufacturing development of Probuphine for clinical study supply and plans for scale-up of production for potential commercial supply.

Guidance provided by the FDA in 2005 as part of the Investigational New Drug (IND) application discussions included a requirement that efficacy of treatment with Probuphine be demonstrated in two adequately controlled studies, and that the safety database include the treatment of approximately 500 patients with Probuphine for six months and approximately 100 patients for one year.

“This is an important meeting with the FDA to review all of the information on Probuphine development, especially the robust Phase 3 clinical results of Probuphine in the treatment of opioid addiction. We also expect to discuss and reach agreement with the FDA on the content and data required for the NDA,” said Katherine L. Beebe, Ph.D., Executive Vice President and Chief Development Officer of Titan. “We believe the strong positive results from the two controlled studies of Probuphine and the follow-on re-treatment studies demonstrate the potential effectiveness of the treatment for opioid addiction and the safety and tolerability of this product. We look forward to our meeting with the FDA and obtaining their guidance on the sufficiency of these data so that we can appropriately plan the timing of our NDA submission.”

About Probuphine
Probuphine is designed to deliver six months of continuous round-the-clock, long-term therapeutic levels of the drug buprenorphine following a single subcutaneous treatment. Buprenorphine, an approved agent for the treatment of opioid addiction, is currently available mainly in the form of sublingual tablet and film formulations. The safety and effectiveness of treatment with Probuphine has been demonstrated in several late-stage and Phase 3 studies conducted to date, including a 163-patient placebo-controlled study which demonstrated clinically meaningful and statistically significant treatment with Probuphine over a 24-week period and was published in the Journal of the American Medical Association (JAMA) and a confirmatory study of 287 patients that showed statistically significant efficacy versus placebo and non-inferiority with a currently marketed sublingual formulation of buprenorphine.

Probuphine was developed using ProNeura™, Titan’s continuous drug delivery system that consists of a small, solid rod made from a mixture of ethylene-vinyl acetate (EVA) and a drug substance. The resulting product is a solid matrix that is placed subcutaneously, normally in the upper arm in a simple office procedure, and is removed in a similar manner at the end of the treatment period. The drug substance is released slowly, at continuous levels, through the process of diffusion. This results in a constant rate of release similar to intravenous administration.

About Titan Pharmaceuticals
For information concerning Titan Pharmaceuticals, Inc., please visit the company’s website at www.titanpharm.com.

The press release may contain “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements include, but are not limited to, any statements relating to the Company’s development program and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in development, testing, regulatory approval, production and marketing of the Company’s drug candidates, adverse side effects or inadequate therapeutic efficacy of the Company’s drug candidates that could slow or prevent product development or commercialization, the uncertainty of patent protection for the Company’s intellectual property or trade secrets, and the Company’s ability to obtain additional financing. Such statements are based on management’s current expectations, but actual results may differ materially due to various factors, including those risks and uncertainties mentioned or referred to in this press release.

SUBOXONE® is a registered trademark of Reckitt Benckiser Pharmaceuticals Inc.