FDA Approves Dsuvia amidst Protests

As I begin my blogging days for the Willow Springs Recovery (https://www.willowspringsrecovery.com), I hope to stay on par with current recovery information that comes across the news.

The Food and Drug Administration has approved Dsuvia (http://www.dsuvia.com/) , a potent opioid, despite dissuasion's from several sectors that the drug will contribute to the ongoing opioid epidemic and will result in an increase in the already alarming number of deaths from overdose.

The FDA’s advisory committee (https://www.fda.gov/advisorycommittees/committeesmeetingmaterials/drugs/anestheticandanalgesicdrugproductsadvisorycommittee/default.htm) recommended in a 10-3 vote on October 12 for the approval of the drug. Dsuvia is sufentanil in a new product form made by AcelRx Pharmaceuticals, Inc., and is a small tablet for sublingual use in a single dose. The FDA generally follows the AADPAC recommendations and approved Dsuvia on Friday, November 2.

In a lengthy press statement (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624968.htm) explaining the approval of the new formulation, FDA Commissioner Scott Gottlieb acknowledged the role of diverted opioids in the current addiction epidemic and that the hard lessons from this are being applied to address the concerns for safety with regards to Dsuvia. He said that distribution and use of this drug will be put under very restricted conditions, particularly under the requirements of Risk Evaluation and Mitigation Strategy (http://dsuviarems.com/).

The current addiction epidemic is complicated by opioids and other drugs being diverted and ending up used by people for whom they are not intended. AcelRX, the manufacturer of Dsuvia contends that the risk of diversion is low considering that it will not be available at pharmacies but only to health care professionals and in health facilities.

The Substance Abuse and Mental Health Services Administration (SAMHSA) reports in the National Survey Drug Use and Health Survey (https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR1-2016/NSDUH-FFR1-2016.htm#opioid) of 2016, that 11.6 million people in the US ( those who are aged 12 and older) have abused opioids in the past year. It also acknowledges that the figures for fentanyl misuse may be understated due to unreported sourcing from illicit manufacturers. Fentanyl is the parent chemical of sufentanil.

The Case for Dsuvia:

Dr. Pamela Palmer, co-founder of AcelRX argues that only a few people misuse drugs from medical centers and will not increase the incidence of outpatient opioid crisis.

Palmer says that as a new product form Dsuvia fills a specific need inasmuch as medical provider put it under patients’ tongue where they dissolve. Giving oral tablets to swallow or giving intravenous or epidural injections can take too long before they give the desired relief from pain. Dsuvia is given as a single 30 microgram dose using an applicator to place the tablet under the patient’s tongue.

She envisions health workers administering the sublingual Dsuvia in cases where swallowing a pill or finding a vein is difficult. An example will be in emergency room cases where the patient is obese and finding a suitable vein will take an unduly long time. She also said that the Department of National Defense, which funded the research for Dsuvia, intends to use sufentanil in the battle fronts as a replacement for morphine. Sufentanil (and Dsuvia) is 500 to 1000 times more potent than the latter. Palmer foresees a $1.1 billion sale for Dsuvia per year.

Criticisms against Dsuvia:

Dr. Raeford Brown, the Chairman of AADPAC, the advisory committee that endorsed the approval of Dsuvia, despite his disagreement and absence from the meeting had exhorted the FDA to reject the drug on October 18 (https://www.citizen.org/sites/default/files/2451.pdf) together with other doctors from the Public Citizen’s Health Research Group. He earlier informed AADPAC that he will not be able to attend the meeting due to conflicting schedules.

Dr. Brown said that approving Dsuvia will not help in any way the previous gains made in the reduction of potent opioids on the streets. Dr. Brown says that the size and potency of Dsuvia are appealing to people who desire to use or sell it.

The other doctors from Public Citizen feel that Dsuvia is unnecessary and is not unique, dismissing AcelRX claims that it fills a crucial need. No test in emergencies was conducted, and two of AcelRx’s own tests (https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AnestheticAndAnalgesicDrugProductsAdvisoryCommittee/UCM622858.pdf) proved that the relief from pain came after 54 and 78 minutes.

As stated by Dr. Palmer Mackie, the director of the Eskenazi Health Integrative Pain Program located in Indianapolis and assistant professor at the Indiana University School of Medicine, although a niche for Dsuvia may eventually be found, there is still the uncertainty of our need for the medicine. One thing we can be sure about, however, is that Dsuvia will be diverted at some level. And are we really in need of another opportunity of a medicine to be diverted?

Even though the final vote of the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) was in favor of the drug with 10 in favor to 3, the Public Citizen argues that the outcome of the vote was manipulated by the FDA towards the medicine’s approval. In a letter (https://www.citizen.org/sites/default/files/2451.pdf) by Public Citizen, they urged the FDA to reject the approval of the sufentanil and stated their reasons.

Dr. Raeford Brown, who has been involved in countless opioid product assessment over four years, is fully aware of the harms that come with opioid compounds and has strong feelings against approving Dsuvia. He even relates cases of opioid misuse in health facilities environment, where he had to resuscitate co-workers, technicians, and medical students.

As the FDA advisory committee chair that is in charge with the evaluation of analgesic products, Dr. Brown was not able to attend the advisory committee meeting held on October 12, 2018, due to a conflict of schedule which the FDA knew about months in advance. And yet the FDA still held the meeting even without the chair of the advisory committee.

The FDA also failed to invite most members of Drug Safety and Risk Management Advisory Committee (DSRMAC), another committee of the FDA who are a frequent part of the committees that discusses regulations of new opioid drugs. According to a spokesperson of FDA, members of the drug safety committee could not attend the meeting because of conflicts to schedule, however, according to Dr. Brown, this was not the full story.

Prior to the deadline of FDA’s final decision, U.S. senators – Richard Blumenthal, Ed Markey, Joe Manchin, and Claire McCaskill, – also sent a letter (https://www.markey.senate.gov/imo/media/doc/letter%20to%20Administrator%20Gottlieb%20on%20Dsuvia.pdf) to the commissioner of FDA, Scott Gottlieb, expressing the same concerns as Dr. Brown and Public Citizen and requested the FDA to reject the approval of Dsuvia until all the members of the Drug Safety and Risk Management Advisory Committee, as well as Dr. Raeford Brown were allowed to participate.

In the end, the FDA still implemented the approval of the drug. And as Dr. Sidney Wolfe expresses the mess and failure of the FDA, all meetings on opioids should never again exclude drug safety.

Charles Watson | @charleswatson00