POSIMIR® (bupivacaine solution) for infiltration use reduced mean pain over 72 hours after arthroscopic subacromial decompression surgery compared with vehicle control and improved several measures of postoperative opioid use.
Innocoll Pharmaceuticals Limited, a commercial-stage biotechnology company and portfolio business of Gurnet Point Capital, announced today the publication of the results of Study BU-002-IM evaluating the safety and efficacy of POSIMIR® (bupivacaine solution) for infiltration use in 107 patients undergoing arthroscopic subacromial decompression. The peer-reviewed paper, entitled “SABER-Bupivacaine Reduces Postoperative Pain and Opioid Consumption After Arthroscopic Subacromial Decompression: A Randomized, Placebo-Controlled Trial,” was published online on May 17, 2022 in the Journal of the American Academy of Orthopedic Surgeons (AAOS) Global Research & Reviews (https://t.co/fsFe6cUYP5).
According to the report, POSIMIR 5 mL administered into the subacromial space at the end of arthroscopic subacromial decompression surgery in this double-blind, randomized, controlled, multicenter study, reduced mean postoperative pain on movement (shoulder flexion to 90 degrees) over 72 hours by 1.3 points on a 0-10 scale compared with vehicle control, a relative reduction of 20% (P=0.012). Simultaneous improvements in postoperative opioid use during the same 72-hour period provided evidence that the observed pain reduction was clinically meaningful. The median time to first request for opioid rescue medication was 12.4 hours among patients treated with POSIMIR compared with 1.2 hours in patients who received vehicle control (P=0.014). The median total opioid consumption in intravenous (IV) morphine milligram equivalents over 72 hours was 4.0 mg in the POSIMIR group vs 12.0 mg in the vehicle control group (P=0.010). The proportion of patients who were opioid free at 72 hours was 40% in the POSIMIR group vs 16% in the vehicle control group (P=0.027).
As reported in the paper, the most common treatment-emergent adverse events (TEAEs with incidence in the Safety population of >2%) were headache (POSIMIR 5.7% vs vehicle control 4.0%), elevated ALT (1.9% vs 8.0%), nausea (1.9% vs 12.0%), musculoskeletal pain (3.8% vs 4.0%), cardiac disorders (1.9% vs 8.0%), skin and subcutaneous tissue disorders (3.8% vs 8.0%), injury and procedural complications (5.7% vs 4.0%), general disorders and administration site conditions (1.9% vs 8.0%), and respiratory, thoracic, and mediastinal disorders (1.9% vs 0.0%). Of 2 serious adverse events reported among patients in these treatment groups, only 1 (intolerance to tramadol in a POSIMIR-treated patient) occurred during the immediate 2-week postsurgical follow-up period, and none was considered related to treatment. There were no TEAEs leading to study discontinuation.
“These very compelling results, demonstrating up to three days of local analgesia after a single intra-operative injection, make POSIMIR an important new tool in treating postoperative pain from arthroscopic subacromial decompression,” said Sten Rasmussen, MD PhD, Professor and Head of Department of Clinical Medicine, Aalborg University, Denmark, the senior author and a principal investigator in the POSIMIR study.
“We are excited to publish the positive results of this pivotal clinical trial of POSIMIR, the second approved product in our portfolio of nonopioid, extended-duration, locally-acting analgesics for postsurgical pain control. As the only company with two non-opioid extended release bupivacaine products on the market, we look forward to bringing POSIMIR to the orthopedic community,” said Louis Pascarella, Innocoll President and Chief Executive Officer.
POSIMIR (bupivacaine solution) for infiltration use contains more bupivacaine in a single dose than any other approved, sustained-release bupivacaine product. It employs a proprietary extended-release technology that enables the continuous release of bupivacaine, a non-opioid local anesthetic, directly to the surgical site for 3 days after administration. POSIMIR was approved in February, 2021 by the US Food and Drug Administration (FDA). POSIMIR is indicated in adults for administration into the subacromial space under direct arthroscopic visualization to produce post-surgical analgesia for up to 72 hours following arthroscopic subacromial decompression. Use in any other surgical procedure is investigational. POSIMIR is a registered trademark of Innocoll Pharmaceuticals Limited.
About Subacromial Decompression Shoulder Surgery
Subacromial decompression is a type of shoulder surgery used to treat impingement syndrome, a common repetitive-use injury that causes pain when the arm is raised over the head. The procedure is performed arthroscopically, meaning that several small incisions are made in the skin and muscle of the shoulder through which a camera (arthroscope) and surgical instruments are inserted during surgery. Arthroscopic subacromial decompression is generally performed as outpatient surgery, and most patients go home within a few hours of surgery. The most intense pain typically occurs during the first 3 days and is often managed with a combination of nerve block and oral opioids. There are over 600,000 surgeries involving arthroscopic subacromial decompression performed each year in the U.S.
About Innocoll Pharmaceuticals Limited
Innocoll Pharmaceuticals Limited is a global biotech pharmaceutical company headquartered in Athlone, Ireland and is a subsidiary of Innocoll Biotherapeutics Holding Limited. The Innocoll group of companies is focused on the development and commercialization of pharmaceutical technologies to meet some of today’s most important healthcare challenges.
Innocoll is a portfolio business of Gurnet Point Capital.
About Gurnet Point Capital
Gurnet Point Capital is a unique healthcare investment platform within the B-Flexion Group and led by a team with deep expertise in an industry for which they share a passion, both as investors and senior executives. GPC invests long-term capital and supports entrepreneurs in building a new generation of companies that deliver outsized returns through active ownership. Based in Cambridge, MA, its remit encompasses life sciences and health care focused businesses, with a particular emphasis on businesses that have high growth potential in the product development and commercialization stages of their evolution. With its strategy of driving best in class operational transformation for these businesses, to create social impact while generating significant economic value, Gurnet is able to deliver differentiated results for its investors and partners. www.gurnetpointcapital.com
Further Information About POSIMIR
INDICATIONS AND USAGE
POSIMIR is a bupivacaine solution indicated in adults for administration into the subacromial space under direct arthroscopic visualization to produce post-surgical analgesia for up to 72 hours following arthroscopic subacromial decompression.
Limitations of Use
Safety and effectiveness have not been established in other surgical procedures, including soft tissue surgical procedures, other orthopedic procedures, including for intra- articular administration, and boney procedures, or when used for neuraxial or peripheral nerve blockade.
POSIMIR has not been studied for use in patients younger than 18 years of age.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: RISK OF POTENTIAL ADVERSE EMBOLIC EFFECTS RESULTING FROM INADVERTENT INTRAVASCAULAR INJECTION. Inadvertent intravascular injection could cause POSIMIR droplets to be deposited in the pulmonary and other capillary beds. Administer POSIMIR into the subacromial space at the end of arthroscopic shoulder surgery. Direct arthroscopic visualization must be used to confirm proper placement of the needle tip before injecting POSIMIR.
POSIMIR is contraindicated in patients with a known hypersensitivity to any amide local anesthetic or to other components of POSIMIR, and in patients undergoing obstetrical paracervical block anesthesia.
WARNINGS AND PRECATIONS
Risk of Potential Adverse Embolic Effects Resulting from Inadvertent Intravascular Injection: Caution should be taken to avoid accidental intravascular injection of POSIMIR. Direct arthroscopic visualization must be used to confirm proper placement of the needle tip in the subacromial space before injecting POSIMIR.
Risk of Joint Cartilage Necrosis with Unapproved Intra-articular Use: The safety and effectiveness of POSIMIR in surgical procedures other than subacromial decompression have not been established, and POSIMIR is not approved for use via intra-articular injection. A study of POSIMIR in dogs following an intra-articular administration demonstrated joint cartilage necrosis.
Risk of Systemic Toxicity: Unintended intravascular injection of POSIMIR may be associated with systemic toxicities, including CNS or cardiorespiratory depression and coma, progressing ultimately to respiratory arrest.
Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness should be performed after injection of bupivacaine. Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness.
Avoid additional use of local anesthetics within 168 hours following administration of POSIMIR. Consider increased monitoring for systemic toxicity in debilitated, elderly, or acutely ill patients.
Methemoglobinemia: Cases of methemoglobinemia have been reported in association with local anesthetic use. If local anesthetics must be used in patients more susceptible to developing clinical manifestations of methemoglobinemia close monitoring for symptoms and signs of the condition is recommended.
Chondrolysis with Intra-Articular Infusion of Local Anesthetics: There have been reports of chondrolysis (mostly in the shoulder joint) following intra-articular infusion of local anesthetics, which is an unapproved use.
Risk of Toxicity in Patients with Hepatic Impairment: Consider reduced dosing and increased monitoring for bupivacaine systemic toxicity in patients with moderate to severe hepatic impairment.
Risk of Use in Patients with Impaired Cardiovascular Function: Care should be taken when considering the use of POSIMIR in patients with impaired cardiovascular function (e.g., hypotension, heartblock). Consider reduced dosing. Monitor patients closely for blood pressure, heart rate, and ECG changes.
Adverse events reported with an incidence greater than or equal to 10% and greater than control following POSIMIR administration in shoulder surgery were dizziness, dysgeusia, dysuria, headache, hypoesthesia, paresthesia, tinnitus, and vomiting.
Adverse events reported with an incidence greater than or equal to 10% and greater than control following POSIMIR administration in soft tissue surgical procedures were anemia, bradycardia, constipation, C-reactive protein increased, diarrhea, dizziness, dysgeusia, headache, nausea, post-procedural contusion (bruising), procedural pain, pruritus, pyrexia, somnolence, surgical site bleeding, visible bruising and vomiting.
Do not dilute or mix POSIMIR with local anesthetics or other drugs or diluents.
Patients who are administered POSIMIR are at increased risk of developing methemoglobinemia when concurrently exposed to drugs associated with methemoglobinemia, which could include other local anesthetics.
Pregnancy: There are no studies conducted with POSIMIR in pregnant women. Bupivacaine is contraindicated for obstetrical paracervical block anesthesia.
Lactation: POSIMIR has not been studied in nursing mothers.
Pediatric: Safety and effectiveness in patients below the age of 18 have not been established.
Geriatric: Consider increased monitoring for local anesthetic systemic toxicity when administering POSIMIR to elderly patients.
Hepatic Impairment: Consider reduced dosing and increased monitoring for bupivacaine toxicity in patients with moderate to severe hepatic impairment.
Renal Impairment: Consider increased monitoring for local anesthetic systemic toxicity when administering POSIMIR to patients with impaired renal function
Full Prescribing Information, including the BOXED WARNING, is available at www.POSIMIR.com
To report SUSPECTED ADVERSE REACTIONS, contact DURECT Corporation at 1-844-767-4647 or FDA at 1‑800‑FDA-1088 or www.fda.gov/medwatch.