POSIMIR®(SABER®-Bupivacaine)

Overview

POSIMIR is an investigational nonopioid analgesic being evaluated for its ability to provide 3 days of continuous local pain relief after surgery. Intended for administration just once at the close of surgery, POSIMIR may be instilled directly into the surgical incision(s) with a blunt-tipped applicator or injected into targeted anatomic spaces under endoscopic guidance. Once placed, clinical and nonclinical studies have shown it to form a biodegradable depot that releases bupivacaine directly to the surgical site at a stable rate for 72 hours.

Based on DURECT's proprietary SABER technology, POSIMIR is anticipated to play a central role in modern multimodal postoperative pain management protocols. It has been studied in open, laparoscopic, and arthroscopic surgeries, and is now undergoing further investigation in a multicenter Phase 3 clinical trial. It has not been approved by the FDA for marketing in the U.S. for any indication.

POSIMIR is being studied for its ability to:

  • Improve postoperative pain control in a wide variety of surgical procedures
  • Reduce the use of postoperative opioids and their attendant side effects
  • Improve postsurgical mobilization and enhance recovery
  • Reduce the duration and cost of hospital stays
  • Reduce the resources required to manage postoperative pain and opioid-related side effects

POSIMIR is an investigational new drug and has not been approved by the FDA for marketing in the U.S. for any indication.

Approximately 72 million surgical procedures are performed annually in the United States. Despite improvements in anesthetic and analgesic techniques, insufficient postoperative pain control remains a significant problem, with a recent study indicating that as many as two-thirds of surgical patients experience moderate-to-extreme pain after surgery.

Opioid pain relievers, though widely used postoperatively, have important limitations. They cause undesirable side effects (most commonly nausea, constipation, and sedation) that can delay mobilization, demand more intensive postoperative care, and lower patient satisfaction. They also pose risks of abuse, misuse, and addiction that have contributed to a serious national public health emergency.

POSIMIR is a nonopioid, locally-acting analgesic whose ability to reduce postoperative pain and lower opioid analgesic use is currently under evaluation. If approved by the FDA, it could fill an important medical need in both the inpatient and outpatient surgical settings.

POSIMIR is currently in Phase 3 clinical development and has not been approved by the FDA for marketing in the U.S. for any indication.

DURECT began enrolling patients in PERSIST, a Phase 3 clinical trial, in November 2015. More than 350 patients undergoing laparoscopic cholecystectomy (removal of the gallbladder) are expected to participate in the two sequential parts of the trial. In Part 1, patients were randomized on a 1:1 basis to receive POSIMIR or placebo as a one-time intra-incisional instillation at the close of surgery. In Part 2, patients are being randomized 1:1 to receive POSIMIR or the active control bupivacaine HCl.

In a previous trial of 50 patients using the same surgical model (laparoscopic cholecystectomy), POSIMIR was shown to reduce pain intensity on movement by approximately 25% (P=0.024) over the first 3 days after surgery compared with the active control bupivacaine HCl. This post hoc analysis used the same statistical methodology as the prespecified primary analysis for the PERSIST trial.

In 2 previous late-stage efficacy trials, POSIMIR significantly reduced postoperative pain and opioid use compared with placebo over the first 72 hours after surgery. Patients undergoing open mesh hernia repair (N=79) showed reductions of 31% (P=0.003) and 80% (P=0.009, post hoc analysis), respectively, in mean pain intensity and median opioid use, while patients undergoing shoulder arthroscopy (N=78) showed reductions of 20% (P=0.012) and 67% (P=0.013), respectively, in these same parameters.

The most common adverse reactions reported in clinical trials (occurring at a rate of at least 5% and more frequently than placebo) were: application site discoloration.

The PERSIST trial, in concert with other trials in the POSIMIR clinical program, is expected to support a robust NDA resubmission to the Complete Response Letter received in February 2014.

In May 2017, DURECT licensed development and commercialization rights in the United States to Sandoz AG. For a description of the associated terms, please see Collaborations.  DURECT retains all rights in the rest of the world.

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There are risks and uncertainties associated with our business. Please see our most recent SEC filings (10-K or 10-Q) for a complete description of these risks and uncertainties, which are incorporated herein by reference.