Noting that upwards of two million individuals in the U.S. alone are thought to suffer from serious opioid addiction, Dr. Mark Sirgo, president and CEO of BioDelivery Sciences Inc., outlined for DDNews how his company and its collaborator Endo Pharmaceuticals are working together to help resolve the problem.
DDNews: Dr. Sirgo, could you describe for our readers the prevalence of opioid dependency in the United States and how your product, Buprenorphine HCl Buccal Film, will help alleviate this serious problem?
Mark Sirgo: Opioid dependence is a significant and undertreated condition in the U.S., with more than two million people dependent on opioids in 2012, according to the National Institute on Drug Abuse. Buprenorphine HCl Buccal Film is under development by Endo Pharmaceuticals Inc. and our company, BioDelivery Sciences Inc. (BDSI), for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. In addition, the Drug Enforcement Agency has classified buprenorphine as a Schedule III controlled substance, which means it has less potential for abuse and addiction than other opioids, such as oxycodone and hydrocodone, that are classified as Schedule II drugs.
Separately, in June 2014, BDSI received approval of its New Drug Application (NDA) for Bunavail (buprenorphine and naloxone) buccal film (CIII) from the U.S. Food and Drug Administration (FDA). Bunavail is indicated for the maintenance treatment of opioid dependence and should be used as part of a complete treatment plan to include counseling and psychosocial support. The product was made available to U.S. pharmacies in November.
Unlike existing sublingual film formulations of buprenorphine, Buprenorphine HCl Buccal Film and Bunavail both depend on a proprietary mucoadhesive technology in the form of a thin film that sticks to the inside of the cheek and dissolves minutes after placement.
BioDelivery Sciences is working to address the problem of opioid dependence both through providing alternative pain management options as well as through the availability of Bunavail for the treatment of those with addiction to opioids.
DDNews: How does your BEMA technology work as a drug delivery system?
Sirgo: Our advanced drug delivery technology, BioErodible MucoAdhesive (BEMA), allows for the efficient and convenient delivery of buprenorphine while potentially overcoming some of the administration challenges presented by the sublingual (under the tongue) dosage forms currently available.
BEMA optimizes drug absorption and patient convenience. Each piece of film consists of a bi-layer water-erodible muco-adhesive layer with active drug, with a water-erodible polymer backing layer. The backing layer of the buccal film helps facilitate the one-way flow of medication. The printed muco-adhesive layer is placed on the inside of the cheek; saliva moistens the layer, causing it to bond with the mucous membrane. The medication is subsequently released and diffuses into the cheek’s blood vessels. The medication is then carried throughout the body by the circulatory system. The film adheres to the oral mucosa in seconds and completely dissolves inside the mouth within minutes.
DDNews: Please describe in more detail how the two pivotal Phase 3 studies were conducted and the significance of the results achieved.
Sirgo: The two pivotal Phase 3 studies for demonstration of safety and efficacy were double-blind, randomized, placebo-controlled, enriched-enrollment studies in patients with chronic lower back pain. One study (BUP-307) was conducted in opioid-experienced subjects, and the second study (BUP-308) was conducted in subjects naïve to opioid therapy. Both studies met the primary efficacy endpoint of change from baseline to week 12 of mean daily pain intensity score from placebo (BUP- 307; p <0.00001; BUP – 308; p=0.001). Buprenorphine HCl Buccal Film was generally well tolerated, demonstrating a low incidence of typical opioid-like side effects. We believe the positive results obtained from these studies offer a clear path forward to potentially providing physicians with a meaningful product to treat chronic pain.
DDNews: What other pain management products are coming down the BDSI pipeline, and are they likely to rely on similar drug delivery technology?
Sirgo: We have completed the randomization of all patients in an ongoing initial pivotal Phase 3 clinical trial for Clonidine Topical Gel for the treatment of painful diabetic neuropathy (PDN). We anticipate that topline results of the study will be available by the end of March 2015. The Phase 3 trial is a multicenter, randomized, double-blind, placebo-controlled study to determine the efficacy and safety of Clonidine Topical Gel in the treatment of pain associated with PDN. In the trial, known as the RHAPSODY Study, subjects were randomized to receive either Clonidine Topical Gel or a placebo gel. Two hundred and sixty-three adult subjects were randomized into the 12-week double-blind treatment phase of the study. This is the first of two pivotal trials that would be required for submission of an NDA to the FDA. FDA has granted Fast Track designation for the program, which recognizes the need of developing new therapies for this serious condition. We plan to begin the second Phase 3 study during the first quarter of 2015.
DDNews: What timeline do you anticipate for your recently filed NDA based on the FDA’s 505(b)(2) approval process?
Sirgo: Buprenorphine Buccal Film was submitted utilizing the FDA’s 505(b)(2) regulatory pathway, which provides for a 10-month review.
DDNews: How does Bunavail, which is now commercially available, compare (or contrast) with Buprenorphine?
- Bunavail is the first and only formulation of buprenorphine and naloxone for buccal (inside of the cheek) administration. Bunavail utilizes the proprietary BEMA technology to deliver buprenorphine. Bunavail offers twice the bioavailability of buprenorphine compared to Suboxone (buprenorphine and naloxone) tablets, requiring only half the dose to achieve plasma concentrations comparable to Suboxone. The use of less drug might help reduce the potential for misuse and diversion and potentially cause fewer opioid-related side effects. Furthermore, Bunavail was demonstrated to be well tolerated and effective in a study of 249 opioid-dependent patients converted from a stable dose of Suboxone film or tablets to Bunavail. In the study, patients switched from Suboxone tablets or films to Bunavail, the incidence of constipation decreased from 41 percent at the time of discontinuation of Suboxone to 13 percent after 12 weeks of treatment with Bunavail.
DDNews: What were some of the biggest challenge to getting Bunavail approved?
Sirgo: We were very fortunate in that we had obtained excellent data on Bunavail prior to the start of the FDA approval process. Specifically, Bunavail was assessed in a Phase 3 clinical study in 249 patients who were converted from Suboxone sublingual tablet or film to Bunavail. In this study, Bunavail demonstrated favorable safety and efficacy in the maintenance treatment of opioid dependence as demonstrated by the high study retention rate and the low frequency of patients with positive urine tests for non-prescribed opioids over the 12-week period. The majority of patients who participated found Bunavail easy to use and pleasant in taste. Additionally, prior to conversion to Bunavail, about 40 percent of patients were experiencing constipation while receiving Suboxone tablet or film, and more than two-thirds of these patients reported resolution of symptoms when they switched from Suboxone to Bunavail.
DDNews: What role has Endo played in BDSI’s developmental efforts and what is likely to be the future of the collaboration?
Sirgo: As a leader in the treatment of chronic pain, Endo has extensive experience supporting patients and their physicians, and we are grateful for their commitment to sharing the development of Buprenorphine HCl Buccal Film. Endo Pharmaceutical holds commercialization rights to Buprenorphine HCl Buccal Film for chronic pain worldwide. BDSI and Endo worked closely together in execution of the two pivotal Phase 3 trials and Endo will be solely responsible for commercialization. We look forward to continuing our work with Endo and making Buprenorphine HCl Buccal Film available to patients who need it.
Mark A. Sirgo, Pharm.D., has been president of BDSI since January 2005 and CEO and director since August 2005. He joined the company in August 2004 as senior vice president of commercialization and corporate development upon the acquisition of Arius Pharmaceuticals, of which he was a co-founder and CEO. Dr. Sirgo has over 30 years of experience in the pharmaceutical industry, including 16 years in clinical drug development, seven years in marketing, sales and business development and 12 years in executive management positions. Prior to his involvement with Arius Pharmaceuticals, he spent 16 years in a variety of positions of increasing responsibility in both clinical development and marketing at Glaxo, Glaxo Wellcome and GlaxoSmithKline where he was responsible for managing the development and FDA approval of Zantac 75 while at Glaxo Wellcome, among other accomplishments. Sirgo received his bachelor’s degree in pharmacy from The Ohio State University and his doctorate from Philadelphia College of Pharmacy and Science.
