Inspirion Delivery Technologies Receives FDA Approval for MorphaBond™ (morphine sulfate) extended-release tablets CII, an Opioid Analgesic Formulated with Abuse-Deterrent Properties

News provided by

Oct 05, 2015, 10:00 ET

VALLEY COTTAGE, N.Y., Oct. 5, 2015 /PRNewswire/ -- Inspirion Delivery Technologies LLC ("Inspirion") announced that the United States Food and Drug Administration (FDA) has approved MorphaBond^™ (morphine sulfate) extended-release tablets, for oral use, CII. MorphaBond is an abuse-deterrent formulation of ER-morphine using physical and chemical barriers, without the use of aversive agents or opioid antagonists.

MorphaBond is formulated with inactive ingredients that make the tablet more difficult to adulterate for misuse and abuse while maintaining extended-release characteristics even if the tablet is subjected to physical manipulation, and/or chemical extraction. MorphaBond has been tested in vitro using methods of manipulation that drug abusers commonly use for preparation of extended-release opioids for administration by various routes, including oral consumption, intranasal insufflation, injection, and smoking. The laboratory test data demonstrated that, relative to morphine sulfate extended-release tablets, MorphaBond has increased resistance to cutting, crushing, or breaking using a variety of tools. When subjected to a liquid environment the manipulated MorphaBond formulation forms a viscous material that resists passage through a needle.

An in vivo clinical abuse potential study was also conducted. "The data from the clinical abuse potential study indicate that MorphaBond has properties that are expected to reduce misuse and abuse via the intranasal route of administration as the extended-release characteristics were largely maintained even after extensive manipulation of the formulation," said Lynn R. Webster, MD, Principal Investigator, PRA Health Sciences, Salt Lake City, UT. "Overall, the results indicate that MorphaBond has properties that are expected to reduce abuse or misuse via injection or insufflation; however, abuse by these routes is still possible," continued Dr. Webster.

"Opioids have been the cornerstone of pain management for many years, however there is a national public health crisis of prescription opioid abuse in the U.S., which is why the development of abuse-deterrent formulations of opioids is an imperative for medicine," said Joseph V. Pergolizzi Jr, MD, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD and Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA. Dr. Pergolizzi went on to say, "Morphine is abused and the development of MorphaBond will offer clinicians another valuable tool as part of a comprehensive approach in the fight against the potential for abuse."

"Extended-release morphine sulfate represents 37% of the more than 17 million prescriptions for Schedule II extended-release opioids in the U.S. alone. With such a large commercial potential and the continued need for more abuse deterrent opioids, MorphaBond can serve as the foundation of a growing specialty pain franchise and company. Inspirion is exploring the best commercial strategy for making this medication available to a prescriber universe that is highly concentrated relative to other therapeutic categories either through an asset sale or commercializing MorphaBond directly," said Stefan Aigner, MD, CEO of Inspirion. Ray DiFalco, President of Inspirion, and Manish S. Shah, MS, RPh, Chief Scientific Officer of Inspirion, the inventors of SentryBond™ technology, added "We believe that the development and commercialization of abuse-deterrent products, like MorphaBond, is an important step to help address the ongoing problem of prescription opioid abuse in the U.S."

In 2012 the National Survey on Drug Use and Health reported that more than 12 million individuals in the U.S. used prescription opioids for non-medical purposes in the previous year and that nearly 70 percent of these non-medical users reported that they obtained them from a friend or family member.¹ According to the Centers for Disease Control and Prevention, from 1999 to 2010, the number of fatal overdoses involving prescription opioids increased four-fold, with 16,300 opioid-related deaths reported in 2010 alone.² Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed MorphaBond and in those who obtain it illegally.

MorphaBond is administered orally every 12 hours and will be available in 15, 30, 60 and 100 mg tablets. MorphaBond should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. Prescribers should review the full prescribing information, which contains important safety and dosing information, prior to prescribing MorphaBond. The FDA-approved prescribing information is available at dailymed.nlm.nih.gov.

PLEASE SEE IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING AND INDICATION BELOW

About Inspirion Delivery Technologies, LLC

Inspirion Delivery Technologies, founded in 2008, is a privately held specialty pharmaceutical company that is dedicated to advancing solutions in the field of prescription drug abuse deterrence through continued innovation. Recognizing the serious unmet public health need to combat the escalating crisis of prescription opioid abuse and misuse, IDT began pioneering the development of novel abuse-deterrent technologies. For more information, visit the Company's website at www.inspiriondt.com.

About SentryBond™

The SentryBond technology platform combines inactive excipients with active pharmaceutical ingredients (API) in a tablet that is specifically designed to frustrate abuse for various methods of manipulation and routes of administration while maintaining an extended-release profile despite physical manipulation and extraction. Inspirion's technology imparts its abuse-deterrent characteristics via physical and chemical methods, without the use of antagonist or aversive agents. SentryBond technology is covered by an issued U.S. patent, with multiple U.S. and global patent applications pending.

INDICATION

MorphaBond (morphine sulfate) extended-release tablets CII is an opioid agonist indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative 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 extended-release opioid formulations, reserve MorphaBond for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
MorphaBond is not indicated as an as-needed (prn) analgesic.

IMPORTANT SAFETY INFORMATION
The full prescribing information for MorphaBond contains the following Boxed Warning:

WARNING: ADDICTION, ABUSE, and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; and NEONATAL OPIOID WITHDRAWAL SYNDROME

Addiction, Abuse, and Misuse

MorphaBond 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 MorphaBond, and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.1)].

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of MorphaBond. Monitor for respiratory depression, especially during initiation of MorphaBond or following a dose increase. Instruct patients to swallow MorphaBond tablets whole; crushing, chewing, or dissolving MorphaBond tablets can cause rapid release and absorption of a potentially fatal dose of morphine [see Warnings and Precautions (5.2)].

Accidental Ingestion

Accidental ingestion of even one dose of MorphaBond, especially by children, can result in a fatal overdose of morphine [see Warnings and Precautions (5.2)].

Neonatal Opioid Withdrawal Syndrome

Prolonged use of MorphaBond 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 [see Warnings and Precautions (5.3)].

DRUG ABUSE AND DEPENDENCE

MorphaBond contains morphine, a Schedule II controlled substance with a high potential for abuse similar to other opioids including fentanyl, hydromorphone, methadone, oxycodone, and oxymorphone. MorphaBond can be abused and is subject to misuse, addiction, and criminal diversion. The high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse.

All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

MorphaBond is for oral use only. Abuse of MorphaBond poses a risk of overdose and death. This risk is increased with concurrent abuse of MorphaBond with alcohol and other substances. Taking cut, broken, chewed, crushed, or dissolved MorphaBond enhances drug release and increases the risk of overdose and death.

The in vitro data demonstrate that MorphaBond has physiochemical properties expected to make abuse via injection difficult. The data from the clinical study, along with support from in vitro data, also indicate that MorphaBond has physicochemical properties that are expected to reduce abuse by the intranasal route of administration. However, abuse by intranasal, intravenous, and oral routes is still possible.

CONTRAINDICATIONS

MorphaBond 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, and hypersensitivity (e.g., anaphylaxis) to morphine.

WARNINGS AND PRECAUTIONS

Serious adverse reactions may occur with MorphaBond which include addiction, abuse, and misuse, life-threatening respiratory depression especially in elderly, cachectic, and debilitated patients. Closely monitor these patients for signs of sedation and respiratory depression, especially when initiating or titrating MorphaBond. Treatment with MorphaBond can cause neonatal withdrawal syndrome, interactions with other CNS depressants, severe hypotension, gastrointestinal adverse reactions, seizures, and withdrawal. When considering MorphaBond in a patient taking a CNS depressant, closely monitor patients for signs of sedation, respiratory depression, and hypotension, and consider using a lower dosage of the concomitant CNS depressant. Monitor patients with a history of seizures for worsened seizure control during MorphaBond therapy.

There is a risk of apnea in patients with chronic pulmonary disease and a risk of increased intracranial pressure in patients susceptible to the effects of CO₂ retention including brain tumors, head injuries, or impaired consciousness. Closely monitor these patients for signs of sedation and respiratory depression, especially when initiating or titrating MorphaBond. Patients should not drive or operate machinery when taking MorphaBond.

Adverse events most frequently observed with morphine sulfate extended-release tablets include constipation, dizziness, sedation, nausea, vomiting, sweating, dysphoria, and euphoric mood. Other adverse reactions reported with morphine sulfate extended-release tablets include amenorrhea, asthenia, bronchospasm, confusional state, drug hypersensitivity, fatigue, hyperalgesia, hypertonia, ileus, increased hepatic enzymes, intestinal obstruction, lethargy, malaise, pulmonary edema, thinking disturbances, somnolence, and vertigo.

DRUG INTERACTIONS

The concomitant use of CNS depressants can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Mixed agonist/antagonist and partial opioid analgesics may reduce the analgesic effect of MorphaBond and/or precipitate withdrawal symptoms.
Morphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
The concomitant use of monoamine oxidase inhibitors (MAOIs) can potentiate the effects of morphine and can increase the risk of hypotension, respiratory depression, profound sedation, come, and death.
Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
The concomitant use of PGP-inhibitors can increase the exposure to morphine by about two-fold and can increase risk of hypotension, respiratory depression, profound sedation, coma, and death.

These are not all the possible side effects of MorphaBond. Please see the full prescribing information for additional important safety and dosing information before prescribing MorphaBond. Advise patients to read the FDA-approved patient labeling (Medication Guide). Patients and health care providers may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

¹Substance Abuse and Mental Health Services Administration. Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD: SAMHSA; 2013.NCHS. Multiple cause-of-death data, 1999–2012. CDC WONDER online database. 2014. Available at: http://wonder.cdc.gov/mcd.html.

² Centers for Disease Control and Prevention. Web-based Injury Statistics Query and Reporting System (WISQARS) [online]. (2014) Available at: http://www.cdc.gov/injury/wisqars/fatal.html. For additional information about Inspirion or MorphaBond contact Kip Martin at:

(732) 907-0438
[email protected]

SOURCE Inspirion Delivery Technologies LLC