Data presented from two Phase 3 trials demonstrating safety and efficacy of buprenorphine HCl buccal film for the management of chronic pain

Endo Pharmaceuticals Inc., a subsidiary of Endo International plc, and BioDelivery Sciences International, Inc. has presented pivotal data from two Phase 3 studies for investigational study drug buprenorphine HCL buccal film utilizing BDSI's patented BioErodible MucoAdhesive (BEMA®) drug delivery technology. The findings, presented at the American Pain Society's 34th Annual Scientific Meeting in Palm Springs, CA, showed BEMA® buprenorphine consistently decreased pain scores compared to placebo. The drug is currently under review by the U.S. Food and Drug Administration (FDA) with a PDUFA action date in October 2015, for use in patients with pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

"In these studies, the investigational study drug BEMA® buprenorphine demonstrated a consistent, statistically significant improvement in patient-reported pain relief," said Joseph S. Gimbel, M.D., Arizona Research Center, Phoenix, and a principal investigator and lead author in one of the studies. "In both trials, BEMA® buprenorphine was effective in reducing pain at every week studied, and in the opioid-experienced trial, the responder analysis was more than twice the rate of placebo. Additionally, the adverse event (AE) profiles were encouraging - the percentage of patients reporting any AE was similar between patients treated with BEMA® buprenorphine or placebo. I am excited at the potential this new product will bring to the medical community if approved."

The Phase 3 studies were both double-blind, randomized, placebo-controlled, enriched-enrollment studies in patients with chronic lower back pain. A total of 971 randomized patients completed both trials, including pain sufferers who either had received opioid therapy (study EN3409-307; abstract 437) or were opioid-naïve at the start of the study (study EN3409-308; abstract 439). The studies included an open-label period in which patients were titrated to a tolerated, effective dose of BEMA® buprenorphine then randomized to either continue on BEMA® buprenorphine or receive a placebo buccal film. The primary endpoint of both studies was change in the average daily pain score from baseline to week 12 of double-blind treatment following the open-label titration period. BEMA® buprenorphine is delivered using BDSI's patented BEMA® drug delivery technology, which efficiently and conveniently delivers buprenorphine across the buccal mucosa (inside lining of the cheek).

Overall, average pain scores increased more in the placebo arm versus BEMA® buprenorphine at week 12 from baseline, and the difference between the two groups was statistically significant:

(EN3409-307/opioid experienced population) mean score change: 1.92, placebo versus 0.88, BEMA® buprenorphine; p<0.00001

(EN3409-308/opioid naïve population) mean score change:1.59, placebo versus 0.94, BEMA® buprenorphine; p=0.0012

A statistically significant percentage of patients on BEMA® buprenorphine experienced pain reductions of greater than 30 percent compared to placebo (EN3409-307: 64.2 percent versus 30.6 percent; p<0.0001; EN3409-308: 62.7 percent versus 46.9 percent; p=0.0012).

"Prescribers often struggle with decisions to initiate treatment for chronic pain, a condition that imposes a significant burden on patients and our society," said Sue Hall, Ph.D., Executive Vice President, Chief Scientific Officer and Global Head of Research & Development and Quality at Endo. "We are pleased with these positive Phase 3 data as they suggest that BEMA® buprenorphine may be an appropriate, effective pain relief option for patients who require around-the-clock treatment. The development of BEMA® buprenorphine builds on Endo's long-standing heritage in meeting unmet needs in pain management, and we look forward to continuing discussions with FDA regarding our accepted regulatory submission."

In study EN3409-307, the most commonly reported adverse events (AEs) - those occurring in greater than 3 percent of patients - included nausea (7.5 percent), vomiting (5.5 percent), and drug withdrawal syndrome (3.5 percent) in the BEMA® buprenorphine group, and nausea (7.4 percent), diarrhea (3.1 percent), drug withdrawal syndrome (9.8 percent) and headache (3.1 percent) in the placebo group. In study EN3409-308, the most commonly reported AEs included nausea (10 percent), constipation (3.9 percent), and vomiting (3.9 percent) with BEMA buprenorphine and nausea (7.3 percent), upper respiratory tract infection (3.9 percent), headache (3.4 percent), and diarrhea (3.0 percent) with placebo.

During the open-label titration phase in EN3409-307, 2 reported serious AEs (ileus and abdominal pain) were considered related to buprenorphine. During the double-blind treatment phase, no serious AEs were considered related to study treatment. There were no deaths during the study. In EN3409-308, no serious AEs that occurred during open-label or double-blind treatment were considered related to study treatment and there were no deaths during the study.

"We believe BEMA® buprenorphine has the potential to be an important treatment option because it combines FDA-approved buprenorphine with BDSI's proprietary BEMA® technology," said Andrew Finn, Pharm.D., Executive Vice President of Product Development for BDSI. "We are excited about these pivotal data results and we believe that, if approved, BEMA® buprenorphine will be a significant step forward for patients and healthcare providers."

Last year, Endo Pharmaceuticals submitted a New Drug Application (NDA) for BEMA® buprenorphine, which was accepted by the FDA in February 2015. At that time, the FDA also granted conditional acceptance for BELBUCA™ as the proposed proprietary name for buprenorphine HCl buccal film. A PDUFA action date has been set for October 2015.

About BEMA® buprenorphine

Buprenorphine is a Schedule III controlled substance, meaning that it has been designated as having lower abuse potential than Schedule II drugs, a category which includes most opioid analgesics. Buprenorphine is a mu-opioid receptor partial agonist and a potent analgesic with a relatively long duration of action. BEMA® buprenorphine is being developed under the proprietary name BELBUCA™ (buprenorphine HCl) buccal film and will be commercialized through a worldwide license and development agreement between Endo Pharmaceuticals and BDSI.