WAYNE, Penn., Jan. 9, 2017 /PRNewswire/ -- Egalet
Corporation (Nasdaq: EGLT) ("Egalet"), a fully integrated specialty
pharmaceutical company focused on developing, manufacturing and
commercializing innovative treatments for pain and other
conditions, today announced that the U.S. Food and Drug
Administration (FDA) has approved ARYMO™ ER (morphine sulfate)
extended-release (ER) tablets C-II 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.
Experience the interactive Multimedia News Release here:
https://www.multivu.com/players/English/7999051-egalet-corp-arymo-er-fda-approval
ARYMO ER is the first approved product developed using Egalet's
proprietary Guardian™ Technology—a physical and chemical barrier
approach to abuse deterrence without the use of an opioid
antagonist—creating tablets that are difficult to manipulate for
the purpose of misuse and abuse. Results from in vitro
testing demonstrated that ARYMO ER tablets, in comparison to
non-abuse-deterrent morphine sulfate extended-release tablets, have
increased resistance to cutting, crushing, grinding or breaking
using a variety of tools. Due to its physical and chemical
properties, ARYMO ER is expected to make abuse by injection
difficult.
"Given the need for treatments for the millions of Americans
living with chronic pain, the growing problem of prescription abuse
and the fact that we know diversion is a huge problem, it is
important that we have more abuse-deterrent treatment options, like
ARYMO ER, if and when these pain treatments end up in the wrong
hands," said Nathaniel Katz, M.D.,
neurologist and pain specialist as well as founder and president of
Analgesic Solutions.
ARYMO ER has been approved in three dosage strengths: 15 mg, 30
mg and 60 mg. The U.S. commercial launch, utilizing Egalet's
established commercial infrastructure, is planned for the first
quarter 2017.
"With the majority of ER opioids in easy to abuse forms, it is
important that healthcare professionals have additional treatment
options like ARYMO ER that are resistant to different methods of
manipulation using a variety of tools," said Bob Radie, president and chief executive officer
of Egalet. "ARYMO ER has physical and chemical properties expected
to make abuse by injection difficult which is important given it is
the most common non-oral route of morphine abuse and the most
dangerous. With our commercial organization in place, we are ready
to launch ARYMO ER in the first quarter of 2017."
The FDA approval of ARYMO ER triggered $40 million in new funding to Egalet from the
second tranche of the senior secured debt financing previously
announced on August 31, 2016. In
connection with the second tranche, the note purchasers will also
receive a royalty right, representing a right to receive an
aggregate 1.5% royalty payment on net sales of ARYMO ER, as further
described in Egalet's current report on form 8-K filed on
September 1, 2016.
Conference Call Information
The approval of ARYMO ER
will be discussed on a conference call today, Monday, January 9, 2017:
Time: 8:15 p.m. EST
Webcast (live and archived):
http://egalet.investorroom.com/eventsandwebcasts
Dial-in numbers:
- 1-888-346-2615 (domestic)
- 1-412-902-4253 (international)
Replay numbers:
- 1-877-344-7529 (domestic)
- 1-412-317-0088 (international)
Conference number: 10093736
Guardian™ Technology
Egalet's Guardian Technology has many applications and has been
used to develop abuse-deterrent forms of commonly abused
prescription medications. Egalet's proprietary Guardian Technology
is a polymer matrix tablet technology that utilizes a novel
application of the well characterized manufacturing process of
injection molding, which results in tablets that are hard and
difficult to manipulate for misuse and abuse. This approach offers
the ability to design tablets with controlled-release profiles as
well as physical and chemical properties that have been
demonstrated to resist both common and rigorous methods of
manipulation. Tablets manufactured with Guardian Technology have
been shown to have increased resistance to physical methods of
manipulation, such as cutting, crushing, grinding or breaking using
a variety of mechanical and electrical tools. They are also
resistant to chemical manipulation and attempts at extraction and
turn into a viscous hydrogel on contact with liquid, making
syringeability very difficult.
About Egalet
Egalet, a fully integrated specialty pharmaceutical company, is
focused on developing, manufacturing and commercializing innovative
treatments for pain and other conditions. Egalet has three approved
products: ARYMO™ ER (morphine sulfate) extended-release tablets for
oral use only –CII, developed using Egalet's proprietary Guardian™
Technology, OXAYDO® (oxycodone HCI, USP) tablets for
oral use only –CII and SPRIX® (ketorolac tromethamine)
Nasal Spray. Using Guardian Technology Egalet is developing a
pipeline of clinical-stage, product candidates including
Egalet-002, an abuse-deterrent, extended-release, oral oxycodone
formulation 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. Guardian Technology
can be applied broadly across different classes of pharmaceutical
products and can be used to develop combination products that
include multiple active pharmaceutical ingredients with similar or
different release profiles. For full prescribing information on
ARYMO ER, including the boxed warning and medication guide, please
visit arymoer.com. For full prescribing information on SPRIX,
including the boxed warning and medication guide, please visit
sprix.com. For full prescribing information on OXAYDO, please visit
oxaydo.com. For additional information on Egalet, please visit
egalet.com.
Safe Harbor
Statements included in this press release that are not historical
in nature and contain the words "anticipate," "believe,"
"estimate," "expect," "intend," "may," "plan," "predict,"
"project," "suggest," "target," "potential," "will," "would,"
"could," "should," "continue," "look forward to" and other similar
expressions are "forward-looking statements" within the meaning of
the Private Securities Litigation Reform Act of 1995. These
forward-looking statements are based on management's current
expectations, and are subject to known and unknown uncertainties
and risks. Actual results could differ materially from those
discussed due to a number of factors, including, but not limited
to: the success of Egalet's clinical trials, including the timely
recruitment of trial subjects and meeting the timelines therefor;
Egalet's ability to obtain regulatory approval of its product
candidates; Egalet's ability to maintain the intellectual property
position of its products and product candidates; Egalet's ability
to identify and reliance upon qualified third parties to
manufacture its products; Egalet's ability to service its debt
obligations; Egalet's ability to raise additional funds to execute
its business plan and growth strategy on terms acceptable to
Egalet, if at all; Egalet's ability to find and hire qualified
sales professionals; the receptivity in the marketplace and among
physicians to Egalet's products; the success of products which
compete with Egalet's that are or become available; general market
conditions; and the Risk Factors set forth in Egalet's Annual
Report on Form 10-K and Quarterly Reports on Form 10-Q filed with
the United States Securities and Exchange Commission (SEC) and in
other filings Egalet makes with the SEC from time to time. In
addition, the forward-looking statements included in this press
release represent Egalet's views only as of the date hereof. Egalet
anticipates that subsequent events and developments may cause its
views to change. While Egalet may elect to update these
forward-looking statements at some point in the future, it
specifically disclaims any obligation to update or revise any
forward-looking-statements contained in this press release whether
as a result of new information or future events, except as may be
required by law.
Important Safety Information for ARYMO™ ER (morphine sulfate)
extended-release tablets, for oral use C-II
WARNING:
ADDICTION, ABUSE, and MISUSE; LIFE-THREATENING RESPIRATORY
DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL
SYNDROME; AND RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR
OTHER CNS DEPRESSANTS
|
Addiction, Abuse,
and Misuse
ARYMO™ ER 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 ARYMO ER, and monitor all
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 ARYMO ER. Monitor for respiratory depression,
especially during initiation of ARYMO ER or following a dose
increase. Instruct patients to swallow ARYMO ER tablets whole;
crushing, chewing, or dissolving ARYMO ER tablets can cause rapid
release and absorption of a potentially fatal dose of
morphine
Accidental
Ingestion
Accidental
ingestion of even one dose of ARYMO ER, especially by children, can
result in a fatal overdose of morphine.
Neonatal Opioid
Withdrawal Syndrome
Prolonged use of
ARYMO ER 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.
Risks From
Concomitant Use With Benzodiazepines Or Other CNS
Depressants
Concomitant use of
opioids with benzodiazepines or other central nervous system (CNS)
depressants, including alcohol, may result in profound sedation,
respiratory depression, coma, and death.
- Reserve concomitant prescribing of
ARYMO ER and benzodiazepines or other CNS depressants for use
in patients for whom alternative treatment options are
inadequate.
- Limit dosages and durations to the minimum
required.
- Follow patients for signs and symptoms of
respiratory depression and sedation.
|
Indications
ARYMO ER 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 extended-release opioid
formulations, reserve ARYMO ER 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.
- ARYMO ER is not indicated as an as-needed (prn) analgesic.
Contraindications
ARYMO ER is contraindicated in patients with: significant
respiratory depression; acute or severe bronchial asthma in an
unmonitored setting or in the absence of resuscitative equipment;
concurrent use of monoamine oxidase inhibitors (MAOIs) or use
within the last 14 days, known or suspected gastrointestinal
obstruction, including paralytic ileus; hypersensitivity (e.g.,
anaphylaxis) to morphine.
Warnings and Precautions
Addiction, Abuse, and Misuse: ARYMO ER contains morphine, a
Schedule II controlled substance. As an opioid, ARYMO ER exposes
its users to the risks of addiction, abuse, and misuse. As
extended-release products such as ARYMO ER deliver the opioid over
an extended period of time, there is a greater risk for overdose
and death due to the larger amount of morphine present.
Life-Threatening Respiratory Depression: Serious,
life-threatening, or fatal respiratory depression has been reported
with the use of opioids, even when used as recommended. Respiratory
depression, 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.
Carbon dioxide (CO2)
retention from opioid-induced respiratory depression can exacerbate
the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression
can occur at any time during the use of ARYMO ER, the risk is
greatest during the initiation of therapy or following a dosage
increase. Closely monitor patients for respiratory depression,
especially within the first 24-72 hours of initiating therapy with
and following and dosage increases with ARYMO ER.
To reduce the risk of respiratory depression, proper dosing and
titration of ARYMO ER are essential. Overestimating the ARYMO ER
dose when converting patients from another opioid product can
result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of ARYMO ER, especially by
children, can result in respiratory depression and death due to an
overdose of morphine.
Neonatal Opioid Withdrawal Syndrome: Prolonged use of ARYMO ER
during pregnancy can result in withdrawal in the neonate. Neonatal
opioid withdrawal syndrome, unlike opioid withdrawal syndrome in
adults, may be life-threatening if not recognized and treated, and
requires management according to protocols developed by neonatology
experts. Observe newborns for signs of neonatal opioid withdrawal
syndrome and manage accordingly. Advise pregnant women using
opioids for a prolonged period of the risk of neonatal opioid
withdrawal syndrome and ensure that appropriate treatment will be
available.
Risks from Concomitant Use with Benzodiazepines or Other CNS
Depressants: Profound sedation, respiratory depression, coma, and
death may result from the concomitant use of ARYMO ER with
benzodiazepines or other CNS depressants (e.g., non-benzodiazepine
sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants,
general anesthetics, antipsychotics, other opioids, alcohol).
Because of these risks, reserve concomitant prescribing of these
drugs for use in patients for whom alternative treatment options
are inadequate.
Observational studies have demonstrated that concomitant use of
opioid analgesics and benzodiazepines increases the risk of
drug-related mortality compared to use of opioid analgesics alone.
Because of similar pharmacological properties, it is reasonable to
expect similar risk with the concomitant use of other CNS
depressant drugs with opioid analgesics.
Life-Threatening Respiratory Depression in Patients with Chronic
Pulmonary Disease or in Elderly, Cachectic, or Debilitated
Patients: The use of ARYMO ER in patients with acute or severe
bronchial asthma in an unmonitored setting or in the absence of
resuscitative equipment is contraindicated.
Patients with Chronic Pulmonary Disease: ARYMO ER-treated
patients with significant chronic obstructive pulmonary disease or
cor pulmonale, and those with a substantially decreased respiratory
reserve, hypoxia, hypercapnia, or pre-existing respiratory
depression are at increased risk of decreased respiratory drive
including apnea, even at recommended dosages of ARYMO ER.
Elderly, Cachetic, or Debilitated Patients:
Life-threatening respiratory depression is more likely to occur in
elderly, cachectic, or debilitated patients because they may have
altered pharmacokinetics or altered clearance compared to younger,
healthier patients.
Monitor such patients closely, particularly when initiating and
titrating ARYMO ER and when ARYMO ER is given concomitantly with
other drugs that depress respiration. Alternatively, consider the
use of non-opioid analgesics in these patients.
Interaction with Monoamine Oxidase Inhibitors: Monoamine oxidase
inhibitors (MAOIs) may potentiate the effects of morphine,
including respiratory depression, coma, and confusion. ARYMO ER
should not be used in patients taking MAOIs or within 14 days of
stopping such treatment.
Adrenal Insufficiency: Cases of adrenal insufficiency have been
reported with opioid use, more often following greater than one
month of use. Presentation of adrenal insufficiency may include
non-specific symptoms and signs including nausea, vomiting,
anorexia, fatigue, weakness, dizziness, and low blood pressure.
Severe Hypotension: ARYMO ER may cause severe hypotension
including orthostatic hypotension and syncope in ambulatory
patients. There is an increased risk in patients whose ability to
maintain blood pressure has already been compromised by a reduced
blood volume or concurrent administration of certain CNS depressant
drugs (e.g., phenothiazines or general anesthetics). Monitor these
patients for signs of hypotension after initiating or titrating the
dose of ARYMO ER. In patients with circulatory shock, ARYMO ER may
cause vasodilation that can further reduce cardiac output and blood
pressure. Avoid the use ARYMO ER in patients with circulatory
shock.
Risks of Use in Patients with Increased Intracranial Pressure,
Brain Tumors, Head Injury, or Impaired Consciousness: In patients
who may be susceptible to the intracranial effects of
CO2 retention (e.g., those with evidence of increased
intracranial pressure or brain tumors), ARYMO ER may reduce
respiratory drive, and the resultant CO2 retention can
further increase intracranial pressure. Monitor such patients for
signs of sedation and respiratory depression, particularly when
initiating therapy with ARYMO ER.
Opioids may also obscure the clinical course in a patient with a
head injury. Avoid the use of ARYMO ER in patients with
impaired consciousness or coma.
Difficulty in Swallowing and Risk for Obstruction in Patients at
Risk for a Small Gastrointestinal Lumen: Moistened ARYMO ER tablets
may become sticky leading to difficulty in swallowing the tablets.
Patients could experience choking, gagging, regurgitation and
tablets stuck in the throat. Instruct patients not to pre-soak,
lick, or otherwise wet ARYMO ER tablets prior to placing in the
mouth, and to take one tablet at a time with enough water to ensure
complete swallowing immediately after placing in the mouth.
Tablet stickiness and swelling may also predispose patients to
intestinal obstruction and exacerbation of diverticulitis. Patients
with underlying GI disorders such as esophageal cancer or colon
cancer with a small gastrointestinal lumen are at greater risk of
developing these complications. Consider use of an alternative
analgesic in patients who have difficulty swallowing and patients
at risk for underlying GI disorders resulting in a small
gastrointestinal lumen.
Risks of Use in Patients with Gastrointestinal Conditions: ARYMO
ER is contraindicated in patients with gastrointestinal
obstruction, including paralytic ileus. The morphine in ARYMO ER
may cause spasm of the sphincter of Oddi. Opioids may cause
increases in the serum amylase. Monitor patients with biliary tract
disease, including acute pancreatitis, for worsening symptoms.
Increased Risk of Seizures in Patients with Seizure Disorders:
The morphine in ARYMO ER may increase the frequency of seizures in
patients with seizure disorders, and may increase the risk of
seizures occurring in other clinical settings associated with
seizures. Monitor patients with a history of seizure disorders for
worsened seizure control during ARYMO ER therapy.
Withdrawal: Avoid the use of mixed agonist/antagonist (i.e.,
pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g.,
buprenorphine) analgesics in patients who have received or are
receiving a course of therapy with a full opioid agonist analgesic,
including ARYMO ER. In these patients, mixed agonists/antagonist
and partial agonist analgesics may reduce the analgesic effect
and/or may precipitate withdrawal symptoms.
When discontinuing ARYMO ER, gradually taper the dose. Do not
abruptly discontinue ARYMO ER.
Risks of Driving and Operating Machinery: ARYMO ER may impair
the mental or physical abilities needed to perform potentially
hazardous activities such as driving a car or operating machinery.
Warn patients not to drive or operate dangerous machinery unless
they are tolerant to the effects of ARYMO ER and know how they
will react to the medication.
Adverse Reactions
In clinical trials, the most common adverse reactions with
morphine sulfate extended-release formulations were constipation,
dizziness, sedation, nausea, vomiting, sweating, dysphoria, and
euphoric mood.
Additional Drug Interactions
Serotonergic Drugs: The concomitant use of opioids with other
drugs that affect the serotonergic neurotransmitter system has
resulted in serotonin syndrome.
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics:
May reduce the analgesic effect of ARYMO ER and/or precipitate
withdrawal symptoms; avoid concomitant use.
Muscle Relaxants: Morphine may enhance the neuromuscular
blocking action of skeletal muscle relaxants and produce an
increased degree of respiratory depression.
Cimetidine: The concomitant use of cimetidine can potentiate
morphine effects and increase risk of hypotension, respiratory
depression, profound sedation, coma, and death.
Diuretics: Opioids can reduce the efficacy of diuretics by
inducing the release of antidiuretic hormone.
Anticholinergic Drugs: The concomitant use of anticholinergic
drugs may increase risk of urinary retention and/or severe
constipation, which may lead to paralytic ileus.
P-Glycoprotein (P-gp) Inhibitors: The concomitant use of P-gp
inhibitors can increase the exposure to morphine by about two-fold
and can increase risk of hypotension, respiratory depression,
profound sedation, coma, and death.
Use in Specific Populations
Pediatrics: The safety and effectiveness in pediatric patients
below the age of 18 have not been established.
Geriatrics: The pharmacokinetics of ARYMO ER have not been
studied in elderly patients. Elderly patients (aged 65 years or
older) may have increased sensitivity to morphine.
Hepatic Impairment: Morphine pharmacokinetics have been reported
to be significantly altered in patients with cirrhosis. Start these
patients with a lower than usual dosage of ARYMO ER and titrate
slowly while monitoring for signs of respiratory depression,
sedation, and hypotension.
Renal Impairment: Morphine pharmacokinetics are altered in
patients with renal failure. Start these patients with a lower than
usual dosage of ARYMO ER and titrate slowly while monitoring for
signs of respiratory depression, sedation, and hypotension
Overdosage
Acute overdosage with morphine can be manifested by respiratory
depression, somnolence progressing to stupor or coma, skeletal
muscle flaccidity, cold and clammy skin, constricted pupils, and,
in some cases, pulmonary edema, bradycardia, hypotension, partial
or complete airway obstruction, atypical snoring, and death. Marked
mydriasis rather than miosis may be seen due to severe hypoxia in
overdose situations.
Please see Full Prescribing Information,
including BOXED WARNING and MEDICATION GUIDE.
Investor and Media Contact:
E. Blair Clark-Schoeb
Senior Vice President, Communications
Email: bcs@egalet.com
Tel: 917-432-9275
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SOURCE Egalet