Findings also show sustained pain relief with BELBUCA™ treatment for up to 48 weeks among
chronic pain sufferers who require around-the-clock pain relief
DUBLIN, June 3, 2016 /PRNewswire/ -- Endo Pharmaceuticals
Inc., a subsidiary of Endo International plc (NASDAQ: ENDP) (TSX: ENL), today announced new data to be presented supporting the
safety and tolerability of BELBUCA™ (buprenorphine) buccal film for the long-term management of chronic pain in patients
requiring around-the-clock opioids. The findings will be presented during a poster session at the International Conference on
Opioids (ICOO 2016) in Boston, which takes place June 5-7.
BELBUCA™ is the first and only buprenorphine formulation developed with a dissolving film that is absorbed through the inner
lining of the cheek for chronic pain management. In the Phase 3, open-label study, many patients receiving treatment with
BELBUCA™ twice daily reported a low incidence of typical opioid-like side effects such as nausea and vomiting during treatment
titration and for up to 48 weeks of daily therapy. The study also found that BELBUCA™ was effective during long-term treatment
and provided sustained pain relief throughout the treatment phase (48 weeks) as measured on the numeric rating scale (NRS).
"Many patients living with chronic pain require long-term treatment to control their suffering, so it is important that
patients have options to manage their pain," said Martin Hale, M.D., Medical Director, Gold Coast
Research, Plantation FL, and one of the study's investigators. "These new findings support the
safety and tolerability of treatment with BELBUCA™ across a broad range of dosage strengths. The data may provide healthcare
professionals with important information when making treatment decisions for patients living with chronic pain who require daily,
around-the-clock opioid treatment and for whom alternative treatment options are inadequate."
The Phase 3, open-label study enrolled 506 patients with moderate to severe chronic pain, requiring continuous
around-the-clock opioid treatment who underwent a dose titration period of up to six weeks followed by a long-term treatment
phase (48 weeks). Among these patients, 435 patients went on to receive long-term treatment (<48
weeks) with BELBUCA™ 300 µg (n=52), 450 µg (n=45), 600 µg (n=141), 750 µg (n=62) or 900 µg (n=135) administered every 12 hours.
The primary endpoint was to determine the long-term safety and tolerability of BELBUCA™ (dosed every 12 hours); the secondary
endpoint was to determine the long-term efficacy of BELBUCA™ (dosed every 12 hours).
In the safety analysis, adverse events (AEs) (> 3%) occurred in 43.1% and 54.0% of patients during the titration (n=506)
and long-term treatment (n=435) phases, respectively. The most common AEs included nausea (10.3%), constipation (5.9%) and
headache (3.6%) during the titration phase, and nausea (8.3%), vomiting (5.1%) and upper respiratory tract infection (4.8%)
during long-term treatment.
For the efficacy endpoint, the average daily pain intensity score during the treatment phase was between 2.9 and 3.1 on a
scale of 0 (no pain) to 10 (worst pain imaginable). In addition, the need for rescue medication to relieve breakthrough pain
decreased from an average of 3 tablets in the titration to 1.1 tablets in the long-term treatment phase.
"BELBUCA™ is the first and only buprenorphine buccal film combining the established safety and proven efficacy profile of
buprenorphine with a novel buccal film delivery system that adds convenience and flexibility of dosing options and presents a
unique approach for chronic pain management," said Susan Hall, Ph.D, Executive Vice President,
Chief Scientific Officer and Global Head of Research & Development and Quality at Endo. "With these new study findings, Endo
is continuing our focus on addressing an important patient need for safe and effective treatment options for long-term pain
relief."
BELBUCA™, distributed and promoted by Endo, was approved by the U.S. Food and Drug Administration (FDA) 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. The FDA approval was based on data from two placebo-controlled, randomized Phase 3 studies
showing that BELBUCA™ provided significant improvement in patient-reported pain relief with a low incidence of typical
opioid-like side effects.
BELBUCA™ is a mu-opioid receptor partial agonist and a potent analgesic with a long duration of action that utilizes patented
BioErodible MucoAdhesive (BEMA®) drug delivery technology from BioDelivery Sciences International, Inc. (NASDAQ: BDSI). Through
this unique delivery system, buprenorphine is efficiently and conveniently delivered across the buccal mucosa (inside lining of
the cheek). 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. Among chronic pain patients taking opioids,
the vast majority are on daily doses of 160 mg of oral morphine sulfate equivalent (MSE) or less. BELBUCA™ is available in seven
dosage strengths for flexible dosing from 75 μg to 900 μg every 12 hours, allowing physicians to titrate BELBUCA™ individually
for patients to a tolerable dose that provides adequate analgesia with minimal side effects.
For more information, visit www.Belbuca.com.
About BELBUCA™
BELBUCA™ (buprenorphine) buccal film is indicated 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.
Limitations of Use
- Because of the 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, reserve BELBUCA™ 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.
IMPORTANT SAFETY INFORMATION about BELBUCA™
WARNING: ADDICTION, ABUSE, and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; and NEONATAL OPIOID
WITHDRAWAL SYNDROME
Addiction, Abuse, and Misuse
BELBUCA™ exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to
overdose and death. Assess each patient's risk prior to prescribing BELBUCA™, and monitor patients regularly for the development
of these behaviors or conditions.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of BELBUCA™. Monitor for respiratory
depression, especially during initiation of BELBUCA™ or following a dose increase. Misuse or abuse of BELBUCA™ by chewing,
swallowing, snorting, or injecting buprenorphine extracted from the buccal film will result in the uncontrolled delivery of
buprenorphine and pose a significant risk of overdose and death.
Accidental Exposure
Accidental exposure to even one dose of BELBUCA™, especially by children, can result in a fatal overdose of
buprenorphine.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of BELBUCA™ during pregnancy can result in neonatal opioid withdrawal syndrome, which may be
life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid
withdrawal syndrome and ensure that appropriate treatment will be available.
CONTRAINDICATIONS
BELBUCA™ is 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
WARNINGS AND PRECAUTIONS
Addiction, Abuse, and Misuse
- BELBUCA™ contains buprenorphine, a Schedule III controlled substance. As an opioid, BELBUCA™ exposes users to the risks of
addiction, abuse, and misuse.
- Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing BELBUCA™, and monitor all patients
receiving BELBUCA™ for the development of these behaviors or conditions. Risks are increased in patients with a personal or
family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The
potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at
increased risk may be prescribed BELBUCA™, but use in such patients necessitates intensive counseling about the risks and
proper use of BELBUCA™, along with intensive monitoring for signs of addiction, abuse, or misuse.
- Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed BELBUCA™ and
in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused.
- Abuse or misuse of BELBUCA™ by swallowing may cause choking, overdose, and death.
- Opioid agonists such as BELBUCA™ are sought by drug abusers and people with addiction disorders and are subject to criminal
diversion. Strategies to reduce the risk include prescribing the drug in the smallest appropriate quantity and advising the
patient on the proper disposal of unused drug.
- Contact a local state professional licensing board or state controlled substances authority for information on how to
prevent and detect abuse or diversion of this product.
Life-Threatening Respiratory Depression
- Serious, life-threatening, or fatal respiratory depression has been reported with the use of buprenorphine, even when used
as recommended. Respiratory depression, from opioid use, if not immediately recognized and treated, may lead to respiratory
arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid
antagonists, depending on the patient's clinical status.
- While serious, life-threatening or fatal respiratory depression can occur at any time during the use of BELBUCA™, the risk
is greatest during initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when
initiating therapy with BELBUCA™ and following dose increases.
- To reduce the risk of respiratory depression, proper dosing and titration of BELBUCA™ are essential. Overestimating the
dose of BELBUCA™ when converting patients from another opioid product may result in fatal overdose with the first dose.
- Accidental exposure to BELBUCA™, especially in children, can result in respiratory depression and death due to an overdose
of buprenorphine.
ADVERSE REACTIONS
- The most common adverse reactions (>5%) reported by patients treated with BELBUCA™ in the
clinical trials were nausea, constipation, headache, vomiting, fatigue, dizziness, somnolence, diarrhea, dry mouth, and upper
respiratory tract infection.
Click here to see
additional Important Safety Information.
Click here to see full Prescribing Information, including boxed Warning.
About Endo International plc
Endo International plc (NASDAQ: ENDP) (TSX: ENL) is a global specialty pharmaceutical company focused on improving patients'
lives while creating shareholder value. Endo develops, manufactures, markets and distributes quality branded and generic
pharmaceutical products as well as over-the-counter medications though its operating companies. Endo has global headquarters in
Dublin, Ireland, and U.S. headquarters in Malvern, PA. Learn
more at www.endo.com.
About Endo Pharmaceuticals Inc.
Endo Pharmaceuticals Inc. is focused on developing and delivering high-value branded pharmaceutical products that meet
the unmet needs of patients. Endo Pharmaceuticals is an operating company of Endo International plc, a global specialty
pharmaceutical company focused on improving patients' lives while creating shareholder value. Learn more at www.endo.com or www.endopharma.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform
Act of 1995 and Canadian securities legislation, including the statements by Drs. Hale and Hall, and other statements regarding
research and development outcomes, efficacy, adverse reactions, market and product potential and availability. Statements
including words such as "believes," "expects," "anticipates," "intends," "estimates," "plan," "will," "may," "look forward,"
"intend," "guidance," "future" or similar expressions are forward-looking statements. Because these statements reflect Endo's
current views, expectations and beliefs concerning future events, these forward-looking statements involve risks and
uncertainties. Although Endo believes that these forward-looking statements and information are based upon reasonable assumptions
and expectations, readers should not place undue reliance on them, or any other forward-looking statements or information in this
news release. Investors should note that many factors, as more fully described in the documents filed by Endo with the Securities
and Exchange Commission ("SEC") and with securities regulators in Canada on the System for
Electronic Document Analysis and Retrieval ("SEDAR), and as otherwise enumerated herein or therein, could affect Endo's future
financial results and could cause Endo's actual results to differ materially from those expressed in this press release. The
forward-looking statements in this press release are qualified by these risk factors. Endo does not assume any obligation to
publicly update any forward-looking statements except as may be required under applicable securities laws.