Introduction
EMBEDA, a formulation of morphine sulfate and naltrexone hydrochloride extended-release capsules, was designed to address the growing concern of opioid abuse. Here, we delve into the clinical trials, market analysis, and projections for this drug.
Clinical Trials and Abuse Deterrence
Phase 4 Studies
Pfizer conducted three Phase 4 studies to evaluate the abuse potential of EMBEDA. Studies ALO-01-10-4005 and ALO-01-10-4004 were double-blind, cross-over studies in non-dependent, recreational opioid users. These studies compared the subjective measures of abuse potential between crushed EMBEDA, crushed extended-release morphine sulfate, and placebo, administered orally and intranasally. The results showed that EMBEDA had significantly lower scores on endpoints such as “drug liking” and “high” compared to extended-release morphine sulfate[1].
Opioid Withdrawal Study
The third study, ALO-01-09-111, assessed the ability of crushed EMBEDA to induce withdrawal symptoms in opioid-dependent patients. Although the study was discontinued early due to a voluntary recall, it indicated that crushing EMBEDA could induce moderate to severe withdrawal symptoms in some patients, highlighting its abuse-deterrent properties[1].
FDA Approval and Labeling
Initial Approval and Recall
EMBEDA was initially approved by the FDA in 2009 but was voluntarily recalled by Pfizer in March 2011 due to a stability issue. After addressing the stability requirement, Pfizer sought to reintroduce EMBEDA to the market[1].
Abuse-Deterrent Labeling
In October 2014, the FDA approved an updated label for EMBEDA, highlighting its abuse-deterrent properties. The label indicates that EMBEDA has properties expected to reduce abuse via oral and intranasal routes when crushed, although abuse by these routes is still possible[2][3].
Market Analysis
Market Introduction and Discontinuation
EMBEDA was redeployed in six different abuse-deterrent strengths in 2015. However, Pfizer decided to discontinue the sale of EMBEDA in 2019, with the medication expected to be unavailable by early 2020. This decision was made despite the lack of generic formulations available[5].
Impact on Workers’ Compensation
The discontinuation of EMBEDA had a minimal impact on workers’ compensation claims, as indicated by transactional data. Alternative treatments were recommended for patients who required ongoing opioid analgesic therapy[5].
Projections and Future Outlook
Postmarketing Studies
The FDA mandated postmarketing studies to assess whether the abuse-deterrent properties of EMBEDA result in a significant decrease in misuse, abuse, and their consequences. These studies were scheduled to be completed by 2020, with potential additional investigations based on the results[4].
Industry Impact
The development and approval of EMBEDA marked a significant step in addressing opioid abuse. However, its discontinuation highlights the challenges in maintaining a balance between providing effective pain management and mitigating abuse risks.
"Prescription opioids are an important treatment option for people with chronic pain. However, misuse and abuse of opioids in the U.S. is a serious societal concern, which is why the development of abuse-deterrent formulations of these medicines is a high priority," said Bob Twillman, Ph.D., Director of Policy and Advocacy, American Academy of Pain Management[2].
Key Takeaways
- Abuse Deterrence: EMBEDA was designed with abuse-deterrent properties, reducing the potential for abuse via oral and intranasal routes when crushed.
- Clinical Trials: Phase 4 studies demonstrated lower abuse potential compared to extended-release morphine sulfate.
- FDA Approval: Updated labeling approved in 2014 highlighted its abuse-deterrent properties.
- Market Discontinuation: EMBEDA was discontinued in 2019 due to business decisions, despite its unique formulation.
- Postmarketing Studies: Ongoing and future studies are crucial to assess the real-world impact of EMBEDA’s abuse-deterrent properties.
FAQs
What is EMBEDA and how does it work?
EMBEDA is an extended-release formulation of morphine sulfate and naltrexone hydrochloride designed to manage chronic severe pain. When taken as directed, naltrexone remains sequestered, but when crushed, it is released to deter abuse.
Why was EMBEDA recalled in 2011?
EMBEDA was voluntarily recalled by Pfizer in March 2011 due to a stability issue that did not meet pre-specified requirements.
What are the abuse-deterrent properties of EMBEDA?
EMBEDA has properties that reduce abuse via oral and intranasal routes when crushed, as indicated by FDA-approved labeling.
Why was EMBEDA discontinued from the market?
Pfizer decided to discontinue the sale of EMBEDA in 2019, although the exact reasons were not fully disclosed.
What are the implications of EMBEDA’s discontinuation for patients?
Patients prescribed EMBEDA need to review their medication therapy with their prescribers to determine if alternative opioid analgesic treatments are necessary.
Are there any generic formulations of EMBEDA available?
No, there are currently no generic formulations of EMBEDA available.
Sources
- Pfizer Reports Results From Three Phase 4 Studies Demonstrating EMBEDA® (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules CII Impact On Drug Liking And Withdrawal Symptoms. Pfizer.
- FDA Approves Abuse Deterrent Labeling for EMBEDA® (morphine sulfate and naltrexone hydrochloride) Extended-Release (ER) Capsules CII. Pfizer.
- Overdose Prevention Activities Timeline - FDA. FDA.
- EMBEDA (morphine sulfate and naltrexone hydrochloride) extended-release capsules CII. FDA.
- Abuse-deterrent opioid analgesic Embeda® expected to be discontinued from the market. UHCC Community and State.
