On Friday, Oct. 12, 2018, AcelRex Pharmaceuticals, Inc. presented its case to the U.S. Food and Drug Administration (FDA) Anesthetic and Analgesic Drug Products Advisory Committee (ADCOM) to discuss the approval of the new drug application (NDA) 209128 for DSUVIA™.

DSUVIA is a small sufentanil pill deposited below the tongue with an applicator. It is a rapid onset, potent opioid. It would be used for the management of moderate-to-severe acute pain in adult patients in hospital settings who require an opioid when there are no adequate alternative treatments.

I testified before the committee as an advocate for people in pain. This provided me with an opportunity to shine a light on the inadequacy of pain treatment for many people today, particularly those with pain associated with cancer.

In an earlier blog, I wrote about how the preparation process to speak before an ADCOM works. I want to share my remarks to show those who might be interested in how individuals can make positive or negative comments about a drug that is being discussed.

I encourage everyone interested in having your voice heard to register to speak at a meeting that you feel is important to you.

Here was my statement in support of DSUVIA to the FDA ADCOM. It has been slightly modified from the version I uploaded to the public docket request for information. This version includes a citation for the New England Journal of Medicine commentary by Dr. Eduardo Bruera.

Hello,

I am Lynn Webster, Vice President of Scientific Affairs for PRA Health Sciences. I am speaking only for myself and have not been compensated for my time or expenses.

Also, I have not been involved in any phase of DSUVIA™ development.

There are two questions I would ask the committee to consider. First, is there a need for an opioid with the characteristics of DSUVIA? And second, is the safety profile of DSUVIA acceptable?

Regarding Need

Everyone recognizes there is a serious opioid crisis in the United States. Many measures have been taken to address this problem. Some efforts have resulted in fewer opioids’ being prescribed. This is not necessarily bad, but it has led to unintended consequences.

Inadequately controlled acute pain can increase the risk of chronic pain. Many academic publications have reported that undertreated pain increases the risk of dementia, memory loss, and premature mortality. As an advocate for people in pain, I want to see the most suffering among us receive the compassionate care they deserve.

Because of risks associated with prescribing opioids, many physicians are choosing not to treat their patients who have severe pain. Even in hospitals, pain is frequently undertreated.

A recent New England Journal of Medicine commentary by Dr. Eduardo Bruera, from MD Anderson, states that his institution has serious shortages of parenteral opioids necessary to provide relief from cancer-related pain.

Unfortunately, his cancer center is not an exception. There is a national shortage of parenteral opioids, particularly in cancer centers as a direct result of government interventions to curb the opioid crisis. Providers are now often forced to find alternative means to meet the needs of their patients and, frequently, the options are inadequate.

Parenteral opioids are desirable due to the immediate and reliable analgesia. Many patients requiring postoperative and palliative pain relief are not able to take oral analgesics. DSUVIA is a rapid onset sublingual analgesic that is similar to parenteral opioids in onset and avoids oral ingestion. Therefore, DSUVIA could help fill an unmet need.

The Second Consideration Is Regarding Safety

I am quite familiar with sufentanil, having used it extensively in the operating room, and in labor and delivery, for years as a practicing anesthesiologist. I also used it off-label with intrathecal delivery systems for chronic pain. It is a potent opioid that can provide clinical benefits to the appropriate patients.

DSUVIA has inherent risks that are typical of other potent opioids, including addiction and overdose deaths. However, the context in which an opioid is used and managed may be more important than the inherent pharmacologic risks of the product.

In other words, we should ask the following questions. For whom is the drug intended, and is there a risk mitigation strategy to ensure the drug is used properly? Who would be authorized to prescribe and dispense the product? How would prescribers and those dispensing the drug be trained to ensure the safest possible use? How can a patient be prevented from taking more than intended?

Since diversion from well supervised hospital settings is very uncommon for all opioids, we can trust there already will be systems in place to mitigate diversion. So the major concern with this product would be inappropriate use. This morning, AcelRex stated that provider education is a key component of their risk mitigation strategy to ensure appropriate use.

Therefore, it would appear that, with a robust provider education program proposed by AcelRex, DSUVIA could help fill an unmet need created by the shortage of parenteral opioids with minimal risk of harm to patients and to society.

Thank you for your attention.

Lynn Webster MD