Raleigh, North Carolina based BioDelivery Sciences International, Inc. (BDSI), a specialty pharmaceutical company with a focus in the areas of pain management and addiction medicine, and its partner Endo Pharmaceuticals Inc. (Endo), a subsidiary of Endo International plc, announced that the U.S. Food and Drug Administration (FDA) has approved BELBUCA (CIII) (buprenorphine HCl) buccal film for patients with chronic pain that is sufficiently severe to require daily, around-the-clock, long-term opioid treatment, and for which alternative treatment options are inadequate.
Opioid analgesics can play an important role in both acute and chronic pain management, exerting their effects by binding to opioid receptors. However, while some of these effects, notably analgesia, are desirable, others such as sedation, nausea, cognitive impairment, dry mouth (also leading to potential accelerated tooth decay and gum disease), and constipation, can be problematic.
And since chronic pain necessitates use of long term treatment, such adverse events can impact quality of life and impede adherence. Additionally, use of long-term therapy can lead to concerns regarding drug abuse, addiction and dependency, and in some cases even death.
BDSI describes Buprenorphine as being a partial mu-opioid receptor agonist and a kappa antagonist, making it unique compared to full mu-opioid agonists such as morphine. A potent analgesic with a relatively long duration of action. Buprenorphine is a Schedule III controlled substance, meaning it is deemed to have lower abuse potential than Schedule II drugs.
However, because of risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with long-acting opioid formulations, BELBUCA is reserved for use in patients for whom alternative treatment options (eg, non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. BELBUCA is not indicated as an as-needed (prn) analgesic.
BELBUCA is also contraindicated in patients with:
• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Hypersensitivity (eg, anaphylaxis) to buprenorphine
Education and training programs that meet FDA requirements are offered by accredited CME/CE providers, and are available to prescribers of extended-release opioids at no or nominal cost. A list of these programs can be found at http://www.er-la-opioidREMS.com or by calling 1-800-503-0784. An FDA-approved patient counseling document for healthcare providers containing important safety information regarding the safe use, storage, and disposal of extended-release opioids can also be obtained or downloaded at http://www.er-la-opioidREMS.com
BDSI’s novel and proprietary BioErodible MucoAdhesive (BEMA) drug delivery technology used in BELBUCA consists of a small, bioerodible polymer film for application to the buccal mucosal membranes (inner lining of cheek). BEMA films are designed to rapidly deliver a dose of drug across the mucous membranes for time sensitive conditions or to facilitate administration of drugs with poor oral (pill) absorption.
BEMA films are designed to:
• Adhere to oral mucosa in less than 5 seconds
• Optimize delivery across the oral mucosa
• Completely dissolve
The first product to be developed and marketed using the BEMA technology was Onsolis (fentanyl buccal soluble film). Following the successful development and approval of the first product utilizing the BEMA technology, BDSI began to apply the same technology to improve the delivery of other therapies, such as buprenorphine and buprenorphine/naloxone. The BEMA technology may also be developed with other active drugs, particularly in conditions where rapid delivery of drug is important, oral dosing is not optimal, or where intravenous line or injections are unavailable or not practical. BDSI owns the worldwide rights to the BEMA drug delivery technology.
A pivotal Phase 3 clinical trial program for BELBUCA consisted of two efficacy studies, both of which were double-blind, randomized, placebo-controlled, enriched-enrollment studies in patients with chronic lower back pain. BUP-307 was conducted in opioid-experienced subjects, while BUP-308 was conducted in opioid therapy naive subjects.
In January 2014, BDSI and Endo announced positive top-line results from the Phase 3 efficacy study in opioid naive subjects (BUP-308). The trial successfully met its primary efficacy endpoint demonstrating significantly (p<0.005) improved chronic pain relief compared to placebo. In July 2014, positive topline results (p<0.0001) were reported from the Phase 3 efficacy study in opioid-experienced subjects (BUP-307). Additional information can be found at https://www.clinicaltrials.gov/ct2/show/NCT01871285?term=Endo+Belbuca&rank=1
“BELBUCA will provide a novel, alternative treatment option for millions of people suffering with chronic pain.” says Dr. Andrew Finn, Executive Vice President of Product Development at BDSI. “Clinical trials demonstrated that twice daily administration of BELBUCA was well tolerated and controlled moderate to severe chronic pain. BELBUCA will also provide healthcare practitioners and their patients with a new buprenorphine treatment option. Buprenorphine is a Schedule III controlled substance, meaning that it has been defined as having lower abuse potential than Schedule II drugs, a category that includes most opioid analgesics.”
Dr. Niraj Vasisht, Senior Vice President of Product Development and Chief Technical Officer at BDSI observes that “Our patented BEMA delivery technology has enabled efficient and effective delivery of buprenorphine across the buccal mucosa and the seven approved dosages of BELBUCA will allow physicians to individualize titration and treatment based on the patient’s analgesic needs.”
The FDA’s approval of BELBUCA also triggered a milestone payment to BDSI from Endo of $50 million, pursuant to a worldwide license and development agreement signed with Endo Pharmaceuticals in January 2012, BDSI for exclusive rights to develop and commercialize BELBUCA for the treatment of chronic pain.
BDSI anticipates that BELBUCA may become commercially available in the U.S. during the first quarter of 2016, which could trigger additional milestone payments from Endo in the future if certain sales milestones are met. BDSI may also be entitled to receive tiered royalties on net sales of BELBUCA that start in the mid-teens.
Based on current operations and forecasts, BDSI estimates that the $50 million dollar milestone payment from Endo, combined with current cash on hand, provides BDSI with sufficient capital to operate its business to approximately the middle of 2017.
“The FDA approval of BELBUCA is a major milestone for BDSI and a tribute to the exceptional working relationship between the teams at Endo and BDSI. I want to thank all of our employees at BDSI for achieving our third product approval,” says Dr. Mark A. Sirgo, President and Chief Executive Officer of BDSI.
BDSI’s development strategy focuses on utilization of the FDA’s 505(b)(2) approval process. This regulatory pathway creates the potential for more timely and efficient approval of new formulations of previously approved therapeutics.
BDSI’s particular area of focus is the development and commercialization of products in the areas of pain management and addiction — areas where BDSI says it believes its drug delivery technologies and products can best be applied to address critical unmet medical needs. BDSI’s marketed products and those in development address serious and debilitating conditions such as breakthrough cancer pain, chronic pain, painful diabetic neuropathy and opioid dependence.
For more information, visit:
BioDelivery Sciences International, Inc.
Endo Pharmaceuticals Inc.