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FDA committee approves AcelRx’s opioid formulation

By a 10-3 vote on Friday, the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee said the benefits of AcelRx’s Dsuvia tablet outweigh the risks for managing moderate-to-severe acute pain in adults in medically-supervised settings.

The FDA does not have to abide by committee decisions, but historically the FDA has followed committee recommendations.

The pill’s manufacturer had been asked by the FDA in a 2017 complete response letter to provide additional data on safety, efficacy and instructions for its use.

“Dsuvia ... has a predictable onset of action of 15 to 30 minutes without the delay of starting an IV. The 24-hour average redosing interval was 3.07 hours. Dsuvia does not have any active metabolites,” Pamela Palmer, MD, PhD, co-founder and chief medical officer of AcelRx said at Friday’s hearing.

“Importantly, the safety and efficacy of Dsuvia in non-opioid tolerant patients was demonstrated across the clinical program and had a safety profile similar to other opioids. With our educational and REMS materials in place, and limiting Dsuvia to medically-supervised settings, where it will be administered by trained medical providers, we believe the benefits of Dsvuia outweigh the risks.”

She added that Dsuvia (sufentanil sublingual tablet, 30 mcg) would be ideal for many patients who have difficulty establishing or maintaining an IV, problems with too much or too little saliva and the tablet dissolves in 6 minutes compared with 30 minutes for a fentanyl tablet.

Vince Angotti, AcelRx CEO, discussed with Healio Family Medicine how the company addressed some of the FDA’s other concerns.

“The FDA suggested we modify the directions for use to better clarify the sublingual space, and they also wanted more confirmation that the health care provider was the one administering the drug,” he said. “We went back and attached instructions to each and every Dsuvia packet and had health care providers administer the drug to mock patients and achieved close to 100% accuracy.”

 

By a 10-3 vote on Friday, the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee said the benefits of AcelRx’s Dsuvia tablet outweigh the risks for managing moderate-to-severe acute pain in adults in medically-supervised settings.

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Mindful of the negative stigma the word opioid can sometimes bring, Angotti also discussed the sufentanil sublingual tablet’s purpose with Healio Family Medicine in the interview prior to the committee meeting.

“We are not, and we will never be, a chronic pain company. You will not see Dsuvia in someone’s medicine cabinet. Dsuvia is only for supervised hospital settings and emergency situations like shoulder separations, long bone fracture, burn or other emergency room visit. This is not a drug for things like lower back pain,” Angotti said.

“The goal here is not to expand opioid use,” he continued. “The goal is, once a physician in a hospital deems an opioid is the best for the patient’s acute pain management, we have a feasible alternative that does not require the use of IV or tubes and can eliminate dosing errors.”

Committee concerns

An FDA official at Friday’s hearing said that although there is a need for drugs that eliminate pain, these drugs must take other factors into consideration.

“Adequate control of acute pain after surgery or after painful procedures is important for helping patients recover. However, the treatment of acute pain must be balanced with public health considerations related to abuse, misuse, and accidental exposure,” Sharon Hertz, MD, director of the FDA’s Anesthesia and Analgesia Drug Products division said.

Several FDA committee members — Steven B. Meisel, PharmD, CPPS, system director of medication safety at Fairview Health Services in Minnesota and Terri L. Warholak, PhD, RPh, professor and assistant dean of the college of pharmacy at the University of Arizona among them — pressed AcelRx representatives for more details about the company’s assurances the tablet would only be administered in hospitals by trained medical employees.

“One of the REMS elements in that health care professionals have read the instructions for use. How would you propose an organization like mine, that has five to six thousand nurses coming and going on a daily basis, ensure they have read these instructions?” Meisel asked.

Palmer explained that many health care organizations now have electronic records to show the training their employees have undertaken, and that AcelRx intends to audit such records regularly.

“We are [also] going to make available single dose applicators with placebos and also provide in-service hospital training to any hospital that requests it. Often hospitals like to do their own training, in which case we will provide training materials to them,” Palmer continued. “The key thing is that the hospital must document the training because we will be auditing for that.”

There were also other committee questions about how the tablets might be dropped or the impact of children accidentally ingesting the drug.

“The two settings ... where this drug might be administered are main places where children might be visiting their parent in the emergency department. Children tend to chew what is in their mouth, do we know what the chew viability is?” committee member Lonnie Zeltzer, MD, who is also director of the pediatric pain and palliative care program at the David Geffen School of Medicine at the University of California at Los Angeles asked.

“[AcelRx] did try to predict these consequences of accidental exposure by children. They went to the literature to see what the clinical consequences would be, but there were a lot of limitations on the data,” LaShaun Washington-Batts, PharmD, of the FDA’s division of risk management explained.

“The overall risk of a dropped pill causing harm [and a child chewing] is extremely low,” Palmer added.

Panel vote
Most committee members thought benefits of the sufentanil sublingual tablet 30 mcg outweighed the risks for abuse, misuse and accidental exposure. There was not as much consensus on whether or not AcelRx provided enough data on safety, efficacy and instructions for sufentanil’s use. Kevin Zacharoff, MD, FACIP, the committee’s acting chair, voted ‘yes’, but said greater clarification on where the drug could be administered was needed.

“Medically supervised setting means so many different things to me that I can imagine that this could end up in surgical centers and walk-in clinics,” he said. “If this medication is going to be administered to a patient over a period of time, then I’m not satisfied in the scope of the definition of medically supervised setting as the presented.”

Jennifer Higgins, PhD, director of research and policy at the Association of Developmental Disability Providers in Massachusetts, also voted ‘yes’ even though she said she felt that sufentanil’s impact in elderly populations had not been fully studied.

“I do still remain concerned about older adults, and their decreased clearance with age and several other factors that make them a very vulnerable population that hasn’t been studied to my satisfaction. I would hope this could be conveyed through labelling if and when we approve the drug,” she said.

One of the ‘no’ voters, Jacqueline A.M. Willacy, RN, of the Department of Veterans Affairs in Washington D.C., said she was concerned on how sufentanil would increase the workload of an already overworked medical community.

“This [medication] will require a lot of patient monitoring ... and a lot more working hours for nurses to keep going back and forth to check on patients. I would recommend it for inpatient settings,” Willacy said.

Next steps

The FDA has set the sufentanil sublingual tablet 30 mcg’s PDUFA date for Nov. 3. Angotti told Healio Family Medicine if the drug is approved on that date, it could be in hospitals and other approved facilities by the first quarter of 2019. - by Janel Miller

Disclosures : Palmer is chief medical officer of AcelRx. Angotti is CEO of AcelRx. Healio Family Medicine was unable to determine other relevant financial disclosures prior to publication.