WAYNE, Pa., Sept. 22, 2016 /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 results from a Category 3
oral human abuse potential (HAP) study and a Category 3 intranasal
HAP study of product candidate ARYMO™ ER (morphine sulfate)
extended-release tablets have been published in Pain
Medicine, the official journal of the American Academy of Pain
Medicine. These two primary publications of the oral and intranasal
HAP studies report that, after manipulation and administration via
the oral and intranasal routes, respectively, ARYMO ER had a
significant reduction in maximum drug liking compared to crushed MS
Contin® (morphine sulfate extended-release tablets) CII and
placebo.
ARYMO ER was developed 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. ARYMO ER
uses Egalet's proprietary Guardian™ Technology, a polymer matrix
tablet technology which is combined with a novel application of
injection molding for the manufacturing of pharmaceutical tablets.
This results in tablets with controlled-release properties as well
as physical and chemical features that have been demonstrated to
resist both common and rigorous methods of manipulation, in order
to deter common routes of abuse. The U.S. Food and Drug
Administration (FDA) Prescription Drug User Fee Act (PDUFA) goal
date for a decision on ARYMO ER new drug application (NDA)
is October 14, 2016.
"The oral and intranasal human abuse potential studies published
in Pain Medicine highlight the broad and robust
abuse-deterrent profile of ARYMO ER that, if approved, can help to
limit accidental misuse and intentional abuse of morphine through
both the manipulated oral and intranasal routes," said Jeffrey Dayno, MD, chief medical officer of
Egalet. "With the vast majority of extended-release morphine
products in abuseable forms, it is important that physicians have
more treatment options like ARYMO ER with properties intended to
deter abuse that, if approved, can potentially help to protect both
patients and the surrounding communities."
Oral Study
Because of the hardness of ARYMO ER
tablets, chewing would be very difficult so the tablets were
maximally manipulated for the oral HAP study. The study was a
single-center, double-blind, triple-dummy, four-way crossover study
conducted to compare the relative abuse potential of manipulated
ARYMO ER to crushed MS Contin and placebo. Thirty-eight subjects
(ages 18 to 55) who were nondependent, recreational opioid users
completed the study. The primary endpoint was maximum drug liking
(Emax); key secondary outcomes included Overall Drug Liking, Take
Drug Again and the Drug Effects Questionnaire. Pharmacokinetic (PK)
parameters were also measured and Abuse Quotients (AQ) were
reported.
Study highlights include:
- Manipulated ARYMO ER demonstrated a statistically significant
reduction in maximum drug liking (Emax) compared to crushed MS
Contin;
- Emax values were 67 for manipulated ARYMO and 74 for crushed MS
Contin (P = 0.007)
- There was no significant difference in Emax drug liking between
manipulated and intact ARYMO ER;
- Overall drug liking and Take Drug Again measures were
numerically lower for manipulated ARYMO ER compared to crushed MS
Contin, but did not reach statistical significance;
- Responses to 'Feeling High' and 'Good Effects' from the Drug
Effects Questionnaire were both statistically significantly lower
for manipulated ARYMO ER compared to crushed MS Contin;
- The Abuse Quotient (AQ = Cmax/Tmax), which measures the rate of
rise of the opioid and is an indicator of abuse potential, was
lower for both intact (5.7) and manipulated (16.4) ARYMO ER
compared to crushed MS Contin (45.9);
- Adverse event profiles of ARYMO ER and MS Contin were similar
and consistent with common opioid-related side effects; no serious
adverse events were reported.
Intranasal Study
This Category 3 abuse-deterrent
intranasal HAP study was a single-center, randomized, double-blind,
double-dummy, active and placebo-controlled, five period crossover
study which assessed the abuse potential of ARYMO ER versus MS
Contin in 46 nondependent, recreational opioid users when taken
intranasally. The primary objective was to compare drug liking
after subjects snorted manipulated ARYMO ER versus crushed MS
Contin. Since ARYMO ER is an extremely hard tablet and difficult to
reduce to small particle sizes amenable to snorting (based on the
outcome of the first phase, physical tampering, of the Category 1
abuse-deterrent studies for ARYMO ER), the manipulation procedure
involved a multi-step process using both mechanical and electrical
instruments to prepare the product to be dosed intranasally. In
addition, the manipulated product was then sieved to yield particle
sizes that would be small enough for the subjects to snort. Both of
these outputs, the full particle sizes and the sieved/small
particle sizes, were included and evaluated as separate arms in the
study. In comparison, MS Contin was prepared via a single-step,
mechanical manipulation process, which did not require sieving as
all particle sizes were small enough to snort.
Top-line results from the study include:
- After maximal manipulation, ARYMO ER demonstrated a
statistically significant reduction in maximum drug liking (Emax;
primary endpoint) compared to crushed MS Contin (p < 0.001);
- This was seen in both of the ARYMO ER arms: manipulated and all
particle sizes snorted as well as manipulated then filtered with
only the smaller particle sizes snorted
- ARYMO ER was statistically superior to MS Contin on the
secondary endpoints of 'overall drug liking' and 'take drug again'
(p < 0.001 for both endpoints);
- On the measures of 'overall drug liking' and 'take drug again,'
both of the ARYMO ER manipulated arms had scores similar to
placebo;
- The 'Abuse Quotient' (a pharmacokinetic indicator of abuse
potential, with higher scores suggestive of greater abuse
potential), for each of the treatment arms was as follows:
- 37.2 for manipulated MS Contin
- 9.2 for manipulated ARYMO ER (all particle sizes)
- 2.3 for manipulated ARYMO ER (filtered/small particle
sizes)
- 5.5 for intact oral ARYMO ER;
- Adverse event profiles of ARYMO ER and MS Contin were similar
and consistent with common opioid-related side effects except for
nasal irritation; no serious adverse events were reported.
Premarketing abuse-deterrent studies have not been proven to
predict real world misuse and abuse of opioids. If approved,
this would be evaluated for ARYMO ER in a post-marketing
abuse-deterrent study to assess its impact on the misuse and abuse
of extended-release morphine products.
To view the full publications, please visit the journal Pain
Medicine at http://painmedicine.oxfordjournals.org/.
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 two approved products: OXAYDO®
(oxycodone HCI, USP) tablets for oral use only –CII and
SPRIX® (ketorolac tromethamine) Nasal Spray. In
addition, using its proprietary Guardian™ Technology, Egalet is
developing a pipeline of clinical-stage, product candidates that
are specifically designed to deter abuse by physical and chemical
manipulation. The lead programs, ARYMO™ ER, an
abuse-deterrent, extended-release, oral morphine formulation, and
Egalet-002, an abuse-deterrent, extended-release, oral oxycodone
formulation, are being developed 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. Egalet's 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 additional information on Egalet, please visit
egalet.com. For full prescribing information on SPRIX, including
the boxed warning, please visit sprix.com. For full prescribing
information on OXAYDO, please visit oxaydo.com.
Safe Harbor
Statements included in this press release
(including but not limited to anticipated labeling for ARYMO ER)
that are not historical in nature 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 related to
execute its business plan and growth strategy in 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 other risk factors described in Egalet's filings
with the United States Securities and Exchange Commission. Egalet
assumes no 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.
Investor and Media Contact:
E. Blair Clark-Schoeb
Senior Vice President, Communications
Email: bcs@egalet.com
Tel: 917-432-9275
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