Ace1Rx Pharma completes final Phase III trial for ARX 04 (sufentanil sublingual tablet)for the management of moderate to severe acute pain.

AcelRx Pharmaceuticals, Inc. announced that in an open-label Phase III trial (SAP303), investigational product candidate ARX 04 (sufentanil sublingual tablet 30 mcg) was well tolerated in the management of moderate-to-severe acute pain in post-operative study patients, including elderly patients and those with organ impairment. Regardless of age and organ function, approximately 2 in 3 patients had no adverse events during the study (63% of all patients, 63% of those aged more than 65 years, 62% of those with hepatic impairment, 70% of those with renal impairment). The most common adverse events were nausea and headache. On a global assessment of ARX 04 as a method of pain control, 90% of healthcare professionals and 87% of patients responded "good" or "excellent.

SAP303 (NCT02662556) is a multicenter, single-arm, open-label Phase III trial that enrolled 140 patients aged over 40 years who were expected to have moderate-to-severe acute pain after surgery. The primary objective of SAP303 was to study the safety of ARX 04 in the post-operative management of moderate-to-severe acute pain. Recruitment included patients aged over 65 years and patients with comorbidities. The mean age for all patients in SAP303 was 54.7 years, and 17% of patients were aged over 65 years. More than 1 in 4 patients (29%) had some degree of baseline hepatic and/or renal impairment. Nearly 7 in 10 patients (69%) were American Society of Anesthesiologists Physical Status Classification II or III (mild or severe systemic disease).

Safety results showed that, overall, there were no differences in adverse events between patients with normal and impaired liver function or between patients with normal and impaired renal function. No clinically meaningful changes from baseline in vital signs or oxygen saturation were observed, and no opioid reversal agents were needed in the study.

The primary and secondary efficacy endpoints showed a reduction in pain intensity starting at 30 minutes after the first dose of ARX 04, followed by 27%, 49%, and 57% reductions in mean pain intensity from a baseline mean pain score of 6.2 at 1 hour, 2 hours, and 12 hours, respectively.

Comment: This announcement marks the completion of the ARX 04 Phase III clinical program, which comprises SAP303 and 2 earlier Phase III trials in patients with moderate-to-severe acute pain: �SAP301, an ambulatory surgery study that reported positive results in 2015 at the American Society of Anesthesiologists annual meeting. �SAP302, an emergency room study that reported positive results in 2016 at the Military Health System Research Symposium (MHSRS). With positive data from all 3 studies, AcelRx intends to submit a new drug application (NDA) for ARX 04 for the treatment of moderate-to-severe acute pain in medically supervised settings with the FDA by the end of 2016.