TITAN PHARMACEUTICALS ANNOUNCES FDA'S ACCEPTANCE OF RESUBMISSION OF NEW DRUG APPLICATION FOR PROBUPHINE
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Agency action expected by Feb. 27, 2016 on Probuphine for maintenance treatment of opioid dependence
SOUTH SAN FRANCISCO, CA – Sept. 28, 2015 – Titan Pharmaceuticals, Inc. (OTCQB: TTNP) announced today that the U.S. Food and Drug Administration has accepted for review the New Drug Application (NDA) for Probuphine®, a six-month subdermal implant containing buprenorphine hydrochloride for the long-term maintenance treatment of opioid addiction. Probuphine was developed utilizing Titan's long-term, continuous drug delivery technology, ProNeura™. The FDA has set Feb. 27, 2016 as a target date for action on the application, which was submitted by Titan's development and commercialization partner Braeburn Pharmaceuticals.
"We are pleased that the FDA has accepted for review the resubmission of the NDA for Probuphine, and will be working with the agency and Braeburn to achieve our goal of offering the first product on the market to provide maintenance treatment of opioid addiction continuously for six months following a single treatment," said Kate Beebe, PhD, Titan's executive vice president and chief development officer.
U.S. Health and Human Services (HHS) Department Secretary Sylvia Burwell recently announced that HHS will move to expand access to medication-assisted-treatment (MAT) by revising the regulations related to the prescribing of buprenorphine to treat opioid dependence. The current cap on the number of patients that can be treated with buprenorphine products by a physician limits the availability of this important medication-assisted-therapy. The HHS revision to the regulation will be developed to provide a balance between expanding the supply of buprenorphine based treatment, encouraging use of evidence-based MAT, and minimizing the risk of drug diversion.
"Opioid addiction has become a significant health epidemic, and greater access to safe and effective treatments is essential," Titan President Sunil Bhonsle said. "As federal officials seek to find a balance between increasing access and minimizing the risk of abuse and diversion, treatment options with an implant such as Probuphine could play an expanding and crucial role in the maintenance treatment of patients."
The Probuphine NDA resubmission includes results from a Phase 3 double-blind, double-dummy clinical study. The study met the pre-specified primary endpoint of non-inferiority, as well as all secondary efficacy endpoints.
Continuous Drug Delivery Technology
The continuous drug delivery system 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 inner part of 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 dissolution. This results in a stable blood level similar to intravenous administration. Such long-term, linear release characteristics are generally desirable as this avoids peak and trough level dosing that poses problems for many Central Nervous System (“CNS”) and other disease settings.
This continuous drug delivery technology was developed to address the need for a simple, practical method to potentially provide continuous drug administration on an outpatient basis over extended periods of up to 6-12 months. In addition to Probuphine, which is the first product to complete clinical testing that has utilized this proprietary continuous drug delivery technology, Titan has conducted initial non-clinical studies with long-term delivery of dopamine agonists demonstrating the potential of this product in the treatment of Parkinson’s disease in non-clinical models of the disease.
Titan Pharmaceuticals, Inc. is a biopharmaceutical Company developing proprietary therapeutics primarily for the treatment of serious medical disorders.
Titan’s principal asset is Probuphine®, the first slow-release implant formulation of buprenorphine hydrochloride (“buprenorphine”), designed to maintain a stable, round-the-clock blood level of the medicine in patients for up to six months following a single treatment. The outpatient treatment of opioid dependence with daily dosed sublingual buprenorphine formulations represents a $1.5 billion market in the U.S., and a seven day transdermal patch formulation of buprenorphine for the treatment of chronic pain was launched in the U.S. in 2011. This novel implant formulation is inserted subdermally in a patient’s upper arm providing continuous medication, and has the potential to enhance patient compliance to treatment, and limit diversion for illicit use and accidental exposure to the sublingual formulations. An FDA-requested Phase 3 study is currently in progress with completion expected in mid-2015 and resubmission of the New Drug Application later in 2015. In December 2012, Titan entered into a license agreement with Braeburn Pharmaceuticals Sprl (“Braeburn”) that grants Braeburn exclusive commercialization rights to Probuphine® in the United States and Canada. Titan received a non-refundable up-front license fee of $15.75 million and will receive a $15 million milestone payment upon the approval of the NDA by the FDA. Additionally, Titan will be eligible to receive up to $165 million upon achievement of specified sales milestones and up to $35 million in regulatory milestones in the event of future NDA submissions and approvals for additional indications, including chronic pain. Titan will receive tiered royalties on net sales of Probuphine ranging from the mid-teens to the low twenties.
Probuphine is the first product to utilize ProNeura™, a novel, proprietary, long-term drug delivery technology. The ProNeura technology has the potential to be used in developing products for the treatment of other chronic conditions, such as Parkinson’s disease, where maintaining stable, round-the-clock blood levels of a drug can benefit the patient and improve medical outcomes.
Finally, Titan has monetized substantially all of the future royalty revenue of 8-10% of net sales of Fanapt® (iloperidone), an atypical antipsychotic compound being marketed in the U.S. for the treatment of schizophrenia by Novartis Pharma AG (“Novartis”). The future royalty revenue has been sold to Deerfield Management (“Deerfield”), a healthcare investment fund, in exchange for cash and debt considerations which have been used to advance the development of Probuphine and for general corporate purposes.
Sunil Bhonsle, M.B.A.
Executive Vice President and Chief Development Officer
Katherine L. Beebe, Ph.D.
Marc Rubin, M.D.
Board of Directors