Braeburn Pharmaceuticals Announces FDA Approves Probuphine® (buprenorphine) Implant: The First Implant for Treatment of Opioid Dependence

Patients and Providers Have a New Option to Combat Opioid Dependence

PRINCETON, N.J.—May 26, 2016—Braeburn Pharmaceuticals announces that the U.S. Food & Drug Administration (FDA) approved Probuphine, the first implant for the maintenance treatment of opioid dependence in patients who have sustained clinical stability on low-to-moderate doses of buprenorphine, specifically 8 mg or less per day. Probuphine delivers buprenorphine continuously for up to six months and should be used as part of a complete treatment program to include counseling and psychosocial support.

“Patients and their doctors now have Probuphine as a new option for the six-month treatment of opioid dependence. Opioid addiction is a chronic disease and should be treated the same way we treat other serious, chronic diseases—with evidence-based medicine,” said President and CEO Behshad Sheldon, Braeburn Pharmaceuticals. “With 78 people in the U.S. dying each day from opioids, it’s important that patients have more treatments to choose from as no one option will work for everyone. Probuphine is the first of what we hope will be many new and innovative approaches to treating this disease. We are grateful to all of the patients, investigators and to NIDA for their help and dedication that has brought us to this point. ”

Buprenorphine is a commonly prescribed medication for the treatment of opioid dependence. Until today, it has only been available in sublingual (oral) formulations. Probuphine received a priority review based on the potential to reduce accidental pediatric exposure.

“Probuphine is the first treatment for opioid dependence that provides long-term delivery of an evidence-based medicine,” said Richard Rosenthal, Professor of Psychiatry, Icahn School of Medicine at Mount Sinai, Medical Director of Addiction Psychiatry, Mount Sinai Behavioral Health System. “Probuphine offers clinically stable patients a new way to continue taking medicine, ensuring the dose prescribed is the dose taken.”

The systemic side effects for Probuphine are similar to those that are seen with buprenorphine and in the Probuphine clinical trials included: headache, insomnia, upper respiratory tract infection, nausea, anxiety, back pain, depression, constipation, and vomiting. In addition, common implant site reactions included pain, itching, redness and swelling.

“Probuphine represents a significant step forward in addressing the serious lack of new treatment options in the last 15 years. With strong support from the President and the Secretary of Health and Human Services this year to expand access to medication assisted treatment, addiction specialists like myself are more confident we will be able to get more patients the treatment they desperately need,” said Kelly J. Clark, MD, MBA, DFASAM, DFAPA, President Elect, American Society of Addiction Medicine, Chief Medical Officer, CleanSlate Centers. “Opioid dependence touches people from all walks of life, no matter their socioeconomic status, race or gender; the more we educate and innovate the better chance we have at reducing the prevalence of this terrible disease.”

“Buprenorphine is an effective treatment for opioid dependence but was previously only available in pill or film formulation which can be lost, forgotten or stolen,” said Frank J. Vocci, Ph.D., president and senior research scientist, Friends Research Institute. “Probuphine’s inherent value as an implant is that patients receive constant levels of buprenorphine for up to six months without having to administer treatment on a daily basis. This is an unprecedented benefit of a treatment for opioid dependence.”

About Probuphine
Probuphine was developed using ProNeura™, Titan Pharmaceuticals’ (NASDAQ: TTNP) continuous drug delivery system that consists of a small, solid implant made from a mixture of ethylene-vinyl acetate (EVA) and a drug substance. The resulting construct is a solid matrix that is placed subdermally, normally in the upper arm in an outpatient office procedure, and removed in a similar manner at the end of the treatment period. Probuphine implants are 26 millimeters long and 2.5 millimeters in diameter, or about the size of a matchstick. Each implant contains the equivalent of 80 mg of buprenorphine and is placed under the skin in the inner side of the upper arm.

INDICATION STATEMENT

PROBUPHINE is indicated for the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of a transmucosal buprenorphine-containing product (i.e., doses of no more than 8 mg per day of Subutex or Suboxone sublingual tablet or generic equivalent).

PROBUPHINE should be used as part of a complete treatment program to include counseling and psychosocial support.

PROBUPHINE is not appropriate for new entrants to treatment and patients who have not achieved and sustained prolonged clinical stability, while being maintained on buprenorphine 8 mg per day or less of a Subutex or Suboxone sublingual tablet or generic equivalent.

WARNING: IMPLANT MIGRATION, PROTRUSION, EXPULSION and NERVE DAMAGE ASSOCIATED WITH INSERTION and REMOVAL

Risk Associated with Insertion and Removal

Insertion and removal of PROBUPHINE are associated with the risk of implant migration, protrusion, expulsion resulting from the procedure. Rare but serious complications including nerve damage and migration resulting in embolism and death may result from improper insertion of drug implants inserted in the upper arm. Additional complications may include local migration, protrusion and expulsion. Incomplete insertions or infections may lead to protrusion or expulsion.

Because of the risks associated with insertion and removal, PROBUPHINE is available only through a restricted program called the PROBUPHINE REMS Program. All Healthcare Providers must successfully complete a live training program on the insertion and removal procedures and become certified, prior to performing insertions or prescribing PROBUPHINE implants. Patients must be monitored to ensure that PROBUPHINE is removed by a healthcare provider certified to perform insertions.

CONTRAINDICATIONS

Hypersensitivity to buprenorphine or any other ingredients in PROBUPHINE (e.g., EVA).

WARNINGS AND PRECAUTIONS

• Serious Complications from Insertion and Removal: Rare but serious complications including nerve damage and migration resulting in embolism and death may result from improper insertion of drug implants inserted in the upper arm. Additional complications may include local migration, protrusion and expulsion. Incomplete insertions or infections may lead to protrusion or expulsion. All Healthcare Providers must successfully complete a live training program on the insertion and removal procedures and become certified in the PROBUPHINE REMS program, prior to performing insertions or prescribing PROBUPHINE implants.
• Addiction, Abuse and Misuse: Buprenorphine can be abused in a manner similar to other opioids. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors.
• Respiratory and CNS Depression: Significant respiratory depression and death have occurred in association with buprenorphine particularly when taken by the intravenous (IV) route in combination with benzodiazepines or other CNS depressants (including alcohol). Consider dose reduction of CNS depressants when used concomitantly.
• Neonatal Opioid Withdrawal Syndrome: Neonatal opioid withdrawal syndrome(NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy.
• Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid.
• Unintentional Pediatric Exposure: In the event an implant protrudes or comes out, keep the implant away from children. Buprenorphine can cause severe, possibly fatal, respiratory depression in children.
• Risk of Opioid Withdrawal with Abrupt Discontinuation: If treatment is temporarily interrupted or discontinued, monitor patients for withdrawal and treat appropriately.
• Risk of Hepatitis, Hepatic Events: Monitor liver function tests prior to initiation and during treatment.
• Risk of Withdrawal in Patients Dependent on Full Agonist Opioids: Verify that patient is clinically stable on transmucosal buprenorphine and not dependent on full agonists before inserting PROBUPHINE.
• Treatment of Emergent Acute Pain: Treat pain with a non-opioid analgesic whenever possible. If opioid therapy is required, monitor patients closely because higher doses may be required for analgesic effect.
• Most common side effects of PROBUPHINE include: headache, insomnia, rhinorrhea, upper respiratory tract infection, nausea, anxiety, back pain, depression, constipation, and vomiting.

Please read the full prescribing information, including boxed warning and Medication Guide, which you can access at https://braeburnpharmaceuticals.com/wp-content/uploads/2016/05/Probuphine-Full-Prescribing-Information.pdf.

To report SUSPECTED ADVERSE REACTIONS, contact Braeburn at 1-844- 859-6341 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

About Opioid Use Disorder and Buprenorphine
Opioid use disorder is a chronic brain disease and one of the fastest growing public health epidemics in America. In the U.S., 2.5 million people struggle with opioid addiction and, according to the Centers for Disease Control, 78 people die each day from the disease. There is a growing body of evidence that opioid addiction is not a choice or a moral failing, but the result of genetic predisposition combined with environmental factors. Nonetheless, individuals struggling with this disease continue to be stigmatized. Research has also shown that opioid use disorder is best treated with a combination of medication and psychosocial support. The majority of individuals with opioid addiction cannot sustain recovery without long-term outpatient medical treatment.

Buprenorphine is a partial opioid agonist, which may help individuals to stop opioid use without experiencing withdrawal symptoms. Buprenorphine is currently only available in oral form and must be taken daily.

About Braeburn Pharmaceuticals
Braeburn Pharmaceuticals, an Apple Tree Partners company, is a pill-free pharmaceutical company delivering precision medicine in neuroscience. Long-acting therapeutic treatment options can be essential to improving patient outcomes and facilitating recovery in neurological and psychiatric disorders, which are often complicated by stigma and present significant public health challenges. Probuphine, Braeburn’s long-acting buprenorphine implant, was approved by the FDA in May 2016. Braeburn’s investigational product pipeline consists of long-acting implantable and injectable therapies for serious neurological and psychiatric disorders, including opioid addiction, pain, and schizophrenia. Braeburn’s pipeline products are at various stages of clinical development and include CAM2038, weekly and monthly subcutaneous injection depot formulations of buprenorphine, being investigated in opioid addiction and pain; a risperidone six-month implant being investigated in schizophrenia; and a novel molecule, ATI-9242, for treatment of schizophrenia. More information on Braeburn, can be found at www.braeburnpharmaceuticals.com.

SOURCE: Braeburn Pharmaceuticals