WAYNE, Pa., Sept. 22, 2016
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."
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.
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.
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.
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
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SOURCE Egalet Corporation