Endo Pharmaceuticals Inc., a subsidiary of Endo International plc, and BioDelivery Sciences International, Inc.(BDSI) 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, California, showed BEMA buprenorphine consistently decreased pain scores compared to placebo. The drug is currently under review by the US 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-naive 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 naive 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 per cent compared to placebo (EN3409-307: 64.2 per cent versus 30.6 per cent; p<0.0001; EN3409-308: 62.7 per cent versus 46.9 per cent; 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, 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 per cent of patients - included nausea (7.5 per cent), vomiting (5.5 per cent), and drug withdrawal syndrome (3.5 per cent) in the BEMA buprenorphine group, and nausea (7.4 per cent), diarrhea (3.1 per cent), drug withdrawal syndrome (9.8 per cent) and headache (3.1 per cent) in the placebo group. In study EN3409-308, the most commonly reported AEs included nausea (10 per cent), constipation (3.9 per cent), and vomiting (3.9 per cent) with BEMA buprenorphine and nausea (7.3 per cent), upper respiratory tract infection (3.9 per cent), headache (3.4 per cent), and diarrhea (3.0 per cent) 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 BELBUCATM as the proposed proprietary name for buprenorphine HCl buccal film. A PDUFA action date has been set for October 2015.

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 BELBUCATM (buprenorphine HCl) buccal film and will be commercialized through a worldwide license and development agreement between Endo Pharmaceuticals and BDSI.

Endo International plc is a global specialty pharmaceutical company focused on improving patients' lives while creating shareholder value. Endo develops, manufactures, markets and distributes quality branded pharmaceutical and generic pharmaceutical products as well as over-the-counter medications though its operating companies.