PARSIPPANY, N.J., Dec. 14 A Phase II trial of a singleintraoperative administration of EXPAREL (DepoBupivacaine) resulted insignificantly reduced pain with activity in the first 8 to 24 hours followingsurgery, when pain is generally greatest, compared to conventional treatment.The results of the multicenter, randomized, double-blind study were presentedin a poster at the Annual Postgraduate Assembly in Anesthesiology in New YorkCity today, by lead investigator Richard Langford, MD, FRCA, Pain andAnaesthesia Research Centre, St. Bartholomew's Hospital, London, UK.
Dr. Langford indicated that EXPAREL provided safe and well-toleratedanalgesia with normal wound healing in all patients and noted that the studyalso showed:
-- Significant reductions in pain with activity in EXPAREL treatedpatients compared to active control
-- A positive trend toward lower opioid use in all EXPAREL groups comparedto active control
-- More patients who received EXPAREL avoided opioids altogether, comparedto active control.
In addition, the study demonstrated dose-proportional sustained plasmaconcentrations which support the prolonged local release of bupivacaine.
Presenting the results, Dr. Langford stated, "In addition to significantlylowering pain scores with activity during the 8 to 24 hours afteradministration, EXPAREL also showed trends of decrease in the number ofpatients using opioids and a decrease in total opioid consumption. This is animportant finding as lowering opioid usage can spare patients from sideeffects, such as sedation, nausea, vomiting and respiratory depression, thatcan adversely affect their recovery."
EXPAREL, a proprietary product of Pacira Pharmaceuticals, Inc., is a novellong-acting, sustained-release formulation of bupivacaine HCL, a localanesthetic widely used for treating postoperative pain. The dose-escalatingstudy evaluated the efficacy, safety, and pharmacokinetics of EXPAREL comparedto bupivacaine HCL in 76 adult male patients (age ranges 48 to 63) in 10hospitals in the UK and Australia. Subjects were randomized into one of fourcohorts and intraoperatively administered either 175mg, 225mg, 300mg or 325mgof EXPAREL or 100mg bupivacaine HCL around the surgical wound by infiltrationimmediately before closure.
-- There was a statistically significant reduction in pain intensity withactivity across all EXPAREL doses during the first 8 to 24 hours after surgerycompared to bupivacaine HCL (P<0.05). Each patient's pain intensity scoreafter surgery ranged from 21 - 31 across all EXPAREL groups compared to 45 -48 for bupivacaine as measured by the Visual Analogue Scale (VAS) at 8, 12 and24 hours.
-- The research also showed a trend toward lower opioid use in all EXPARELgroups compared to active control.
-- More patients in the EXPAREL groups completely avoided opioids 71% to83% across doses, versus 50% for the bupivacaine groups.
-- Pharmacokinetic findings showed that a single intraoperativeinfiltration of EXPAREL resulted in dose-proportional sustained (72 hours)plasma concentrations of bupivacaine (>100mg/mL).
Safety assessments reported in the poster found EXPAREL to be safe andwell-tolerated. Wound healing was normal in all EXPAREL subjects with nosignificant differences between cohorts. Adverse events were generally mild tomoderate with no significant differences between cohorts and no seriousadverse events were attributed to the study drug.
Inguinal hernia repair is one of the most common operations in routinesurgical practice. In the U.S., more than 600,000 procedures are performedannually with a majority performed on an out-patient basis, according to theNational Center for Health Statistics.
The Potential of EXPAREL
"The anesthesiology and surgical community recognizes the need for newapproaches to postoperative pain management and welcomes the potential advanceEXPAREL presents in overcoming limitations of conventional bupivacaineformulations," said Ronald Burch, M.D., PhD, Chief Medical Officer, Pacira."EXPAREL, currently in late Phase III clinical development, is being studiedin several different types of surgical procedures where postoperative painmanagement is especially problematic and where the need for prolongedanalgesia via a single administration can provide a significant improvement inpain relief, especially during the first 72-hours following surgery when painis the most intense."
EXPAREL is the latest product to benefit from Pacira's proprietarysustained-release DepoFoam(R) technology. DepoFoam technology is designed toaddress the limitations of widely used medications by enhancing their dosingand/or administration profile. It achieves this by encapsulating the drug inmultivesicular liposomal particles which then release the drug over a desiredperiod of time without altering the drug molecule. DepoFoam is a proventechnology that is already used in two commercially available products in theU.S. and Europe.
Pacira Pharmaceuticals, Inc. is an acute care specialty pharmaceuticalcompany founded in March, 2007 through the acquisition of the formerSkyePharma PLC injectable business, for which an experienced management teamwas assembled to address the needs of the acute care market. The company'smost advanced product, EXPAREL(TM) (DepoBupivacaine), a bupivacaine-basedproduct intended to deliver postoperative pain relief by infiltration, is inlate Phase III clinical development. Pacira will also study EXPAREL for nerveblock, non-surgical pain such as long bone fracture and for intraarticularinjection. EXPAREL benefits from the proprietary DepoFoam Technology owned byPacira. Two other DepoFoam-based products -- DepoDur(R) andDepoCyt/DepoCyte(R) -- are marketed by partners in several global territories.The DepoFoam technology also forms the basis of multiple development projectsproviding Pacira an opportunity to expand its pipeline. Pacira owns two cGMPproduction facilities which produce the two approved products, EXPARELclinical development and all pipeline materials.
Additional information about Pacira is available at www.pacira.com.
This news release and the anticipated presentation contain forward-lookingstatements that involve risks and uncertainties, including statements relatingto initiation and progress of the Company's clinical trial programs and thepreliminary results from the clinical trials. Actual results could differmaterially from those projected and the Company cautions readers not to placeundue reliance on the forward-looking statements contained in the release andanticipated presentation.
-- "A single administration of DepoBupivacaine(TM) intraoperative resultsin prolonged detectable plasma bupivacaine and analgesia in patientsundergoing inguinal hernia repair" by Richard M. Langford, FRCA; G.M Chappell,FRACS; Jeff A. Karrasch, FRACP, poster presented December 14, 2008 at thePostGraduate Assembly in Anesthesiology (PGA) of the New York State Society ofAnesthesiologists, is available at www.pacira.com
-- Pacira Pharmaceuticals executives are available for interviews uponrequest.
CONTACT: Taunia Markvicka, 973-254-3565.
SOURCE Pacira Pharmaceuticals, Inc.