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First Transmucosal Opioid for Treating Moderate to Severe Pain in a Medical Setting Enters Path to Approval

November 7, 2017
With Pamela Palmer, MD, PhD

Opioid pharmacology is driving new drug discovery efforts, according to a symposium presented at the American Society of Anesthesiologists’ annual meeting in late October. In the “Frontiers on Opioid Pharmacology”1 at Anesthesiology 2017, experts discussed how the industry is not only changing the way they use existing opioids but also pursuing new opioids with increased efficacy and safety profiles.

One such new drug is a sufentanil sublingual tablet (DSUVIA). The investigational medication contains 30 mcg of sufentanil, formulated into a very small, sublingually absorbed tablet that is delivered through a disposable, prefilled, single-dose applicator (SDA) the size of a sesame seed. AcelRx Pharmaceuticals is developing DSUVIA for the management of moderate-to-severe acute pain in a variety of medically supervised settings, including in emergency medicine; outpatient or ambulatory surgery; non-surgical patients experiencing pain in the hospital; or post-operative patients, following short-stay surgery, who do not require more long-term analgesia.

“This will be the first transmucosal opioid approved for moderate-to-severe acute pain in medically supervised settings that can be used in opioid-naïve patients,” Pamela Palmer, MD, PhD, co-founder and chief medical officer of AcelRx Pharmaceuticals, told Practical Pain Management. “Transmucosal fentanyl products have rapid onsets of analgesia, but they are indicated for those who are already taking opioids and have developed tolerance, and transmucosal buprenorphine products are not approved for acute pain conditions.”

Formulation and Drug Delivery Offer Unique Benefits

DSUVIA’s onset of action is 15 minutes and it may be given to patients who are “NPO,” meaning they cannot take food or liquids. Despite its demonstrated safety in a wide range of patients, DSUVIA will have a Risk Evaluation and Mitigation Strategy (REMS) to increase the safety of the environment in which it is administered, explained Dr. Palmer.

Having a sublingual form of sufentanil offers clinicians the potential to “replace the messy, old-fashioned way of delivering drugs,” said Dr. Palmer. DSUVIA is designed to reduce moderate-to-severe acute pain and dosing errors associated with IV administration via its non-invasive single-dose applicator. “Available in a prefilled dosage form, DSUVIA can eliminate the iatrogenic errors caused by cases of IV opioid misdosing as well as any issues around the current practice of having to witness the wastage, or discarding, of controlled substances following IV administration,” she explained.

SufentanilNew transmucosal sublingual sufentanil tablet may offer easier dosing and drug delivery.

Featured as one of eight top abstracts1 in the symposium, the DSUVIA presentation included a pooled analysis of four clinical trials on efficacy and safety. In these trials, DSUVIA met all primary and most secondary endpoints in studies that included populations of patients mixed age, weight, and comorbidities.

  • In a multicenter, open-label single-arm trial, 140 older adult patients with postoperative pain, many of whom had comorbidities, were given 30 mcg tablets. Using a 100-point pain intensity scale, the differences between the score at baseline and at various time points throughout the 12-hour period were totaled. The sum of the scores, or the Time-weighted Summed Pain Intensity Difference (SPID), over the 12-hour study period averaged 36.04 among the participants.  
  • In the emergency room setting, 76 patients who were given 30 mcg of sufentanil sublingual in an open-label single-arm trial were assessed at points over a one-hour period using a pain intensity scale from 0 to 10. In these patients, the mean SPID was 2.11.
  • A multicenter, randomized, double-blind study comparing sufentanil sublingual with placebo over 12 hours following abdominal surgery showed a mean SPID of 25.84 in those receiving sufentanil and 13.14 in those receiving placebo. The pain intensity scores were based on a scale from 0 to 10.
  • A trial of adult patients randomized to either 20 mcg of sufentanil, 30 mcg of sufentanil, or placebo and assessed every hour for 12 hours after bunionectomy showed a significant difference between SPID values for the 30-mcg tab compared with placebo. In this study, the pain intensity scale ranged from 0 to 10. The mean SPID for sufentanil 30 mcg was 6.53 and for placebo, -7.12. Minus scores indicate an increase in pain. The results for the 20-mcg dose were not significant.

On the Path to FDA Approval

Following an NDA submission in 2016, AcelRx received a Complete Response Letter from the FDA in October 2017 regarding its NDA for DSUVIA, 30 mcg sufentanil sublingual tablet. The agency requested additional safety data for patients who received the maximum dose described in the labeling and changes in the Directions for Use to ensure proper administration of the tablet. “We feel we can accommodate these CRL requests and hope for the availability of an end-of-year meeting with the FDA,” Dr. Palmer said, anticipating final approval in 2018. The new medication will be indicated for the relief of moderate-to-severe acute pain within medically supervised settings.

DSUVIA is funded in part by the Clinical and Rehabilitative Medicine Research Program (CRMRP) of the US Army Medical Research and Material Command, which was established in 2008 to foster research and technology advances for regeneration, restoration, and rehabilitation of traumatic injuries. 

Last updated on: November 9, 2017
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