FDA Approves New Opioid Despite Controversy

On Friday, November 2nd, FDA announced its approval of Dsuvia™, a highly potent synthetic opioid manufactured by AcelRx Pharmaceuticals, Inc.  The drug is a sublingual (under the tongue) formulation of sufentanil that is injected with a disposable, pre-filled, single dose syringe.  “Dsuvia is indicated for the management of acute pain in adults that is severe enough to require an opioid analgesic in certified medically supervised healthcare settings, such as hospitals, surgical centers, and emergency departments.”

Dsuvia’s safety and efficacy were evaluated in a randomized, double-blind, placebo controlled clinical trial.  The trial included 161 patients ranging from 18 to 69 years of age suffering from acute postoperative pain with an intensity of at least four (on a 0-10 numeric rating scale) following abdominal surgery.  During the study, patients received either 30 mcg of Dsuvia or the placebo as needed with at least 60 minutes between doses.  Morphine sulfate 1 mg IV was also available as rescue medication during the trial.

In its press release announcing the product’s approval, AcelRx states that “patients using Dsuvia had a statistically significantly greater SPID12 than patients using placebo. Approximately 22% of patients in the DSUVIA group and 65% of patients in the placebo group took rescue medication within the first 12 hours of the treatment phase.”

The safety of Dsuvia was evaluated through controlled and uncontrolled studies including a total of 646 patients.  Study participants were suffering from moderate-to-severe postoperative pain or pain due to trauma requiring opioid analgesia.  “The most frequently reported adverse reactions ≥ 2% in the randomized, placebo-controlled trial were nausea, headache, vomiting, dizziness, and hypotension. The DSUVIA clinical program builds upon the established safety and efficacy of the reference product, sufentanil citrate injection, which has been in commercial use for over three decades.”

AcelRx anticipates the commercial launch of Dsuvia to take place in the first quarter of 2019.

Controversy Surrounding Dsuvia’s Approval

Dsuvia’s approval has been rather controversial as it comes in the midst of the opioid epidemic that has been afflicting the US for years.  In a recent statement regarding this controversy, FDA Commissioner, Scott Gottlieb, MD, states that the drug “has some unique features in that the drug is delivered in a stable form that makes it ideally suited for certain special circumstances where patients may not be able to swallow oral medication, and where access to intravenous pain relief is not possible. This includes potential uses on the battlefield.” For this reason, AcelRx worked closely with the Department of Defense (DoD) throughout the development of Dsuvia.

The approval came after the chair of FDA’s Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC), Raeford Brown, Jr., M.D., F.A.A.P., along with representatives of the Public Citizen’s Health Research Group sent a letter to the FDA urging the Agency to reject the sublingual sufentanil tablets. In the letter, the group stated that Dsuvia is five to ten times more potent than fentanyl, and 1,000 times more potent than morphine. The group then goes on to list three main reasons why the drug should not be approved and how it could add to the growing opioid epidemic in the US.

Overcoming Controversy

Although the FDA’s statement did not directly mention Dr. Brown’s letter, Dr. Gottlieb did address a number of the concerns it included. He indicated that Congress has directed the Agency to take a new approach to identifying the benefit-risk evaluation of opioids, of which it has already began implementing. He also states that he has asked the professional staff at the FDA and the Opioid Policy Steering Committee to evaluate a new and transparent framework for opioid analgesic approvals.  Gottlieb states that the Agency will eventually issue a guidance document, which will clearly delineate this new process and outline how FDA intends to consider the benefits and risks of opioid products amidst the crisis.

Limitations on Dsuvia’s Use

Furthermore, Gottlieb states that there will be strong limitation of Dsuvia’s use.  The product cannot be dispensed to patients for home use and is not to be used for more than 72 hours, which means it will not be available at retail pharmacies.  The Agency took these measures to restrict the use of Dsuvia to prevent the misuse and abuse of the product and reduce the potential for diversion.  “Because of the risks of addiction, abuse and misuse with opioids; Dsuvia is also to be reserved for use in patients for whom alternative pain treatment options have not been tolerated, or are not expected to be tolerated, where existing treatment options have not provided adequate analgesia, or where these alternatives are not expected to provide adequate analgesia. Like all opioids, Dsuvia will also carry a boxed warning about the serious risks of misuse and abuse, which can lead to addiction, overdose and death. It also includes a boxed warning about the serious risks, including extreme sleepiness, respiratory depression, coma and death, side effects that may be potentiated by the combined use with central nervous system depressants such as drugs called benzodiazepines.”

In conclusion, Dr. Gottlieb reiterates that it is FDA’s responsibility to help combat the opioid crisis all while finding a balance between overall risks and patient needs.  Over the past few years, the FDA has been committed to overcoming the opioid epidemic and has made several monumental strides in doing so, including:

• Participation in Interpol’s annual Operation Pangea XI
• Publication of a draft guidance regarding endpoints for medication-assisted treatment (MAT) & the expansion of MAT for opioid addiction
• Public discussions regarding the impact of abuse deterrent opioids
• Removal of Opana ER from the market
• Approval of implant device to treat opioid addiction
• Publication of a draft guidance regarding abuse-deterrent generic opioids
• Increased labeling requirements for immediate-release opioids

*This list is not intended to be illustrative of all opioid-related regulatory actions taken by FDA.

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