SkyePharma and Endo Announce FDA Approval of DepoDur(TM) (previously referred to as DepoMorphine(TM)) Innovative Single Epidural Injection to Provide 48 Hours of Post-Surgical Pain Relief LONDON and CHADDS FORD, Pa., May 19 /PRNewswire-FirstCall/ -- SkyePharma PLC and Endo Pharmaceuticals today announced that the US Food & Drug Administration (FDA) has approved SkyePharma's New Drug Application (NDA) for DepoDur(TM) for the treatment of pain following major surgery. Previously referred to as DepoMorphine(TM), DepoDur(TM) is a novel single dose sustained-release injectable formulation of morphine. Michael Ashton, Chief Executive of SkyePharma, said: "The FDA's decision to approve DepoDur(TM) is a tremendous vindication of our faith in the product. DepoDur(TM) represents the largest single commitment SkyePharma has made to product development, including funding the product through Phase III trials and building and sustaining a purpose-built manufacturing plant. We expect its commercialisation to have a profound effect on the company's future. Our clinical trial programme for DepoDur(TM) involved over 1000 patients in four different pain models and demonstrated the great potential of the product to improve the control of post-operative pain. We and our partners look forward to the benefits this product will bring for many patients after surgery." Endo's Chairman and Chief Executive Officer Carol A. Ammon said: "We are delighted with the FDA's decision on DepoDur(TM). We believe the approval of DepoDur(TM) is an important step in fulfilling our vision of building our franchise in pain management as well as extending our reach into complementary therapeutic areas such as anaesthesiology." She added that Endo expects to be in a position to commercialize DepoDur(TM) by the end of 2004 provided SkyePharma is able to provide sufficient inventory to support the launch of the product. "We look forward to the commercialization of DepoDur(TM) and believe it provides a novel approach to the treatment of post-operative pain benefiting patients undergoing major surgery." For further information please contact: SkyePharma PLC +44 207 491 1777 Michael Ashton, Chief Executive Officer Peter Laing, Director of Corporate Communications +44 207 491 5124 Sandra Haughton, US Investor Relations +1 212 753 5780 Buchanan Communications +44 207 466 5000 Tim Anderson / Mark Court Endo Pharmaceuticals +1 610 558 9800 Bill Newbould, Vice President, Corporate Communications Lauren Topf +1 212 798 9730 Cohn & Wolfe Notes for editors: SkyePharma PLC develops pharmaceutical products benefiting from world- leading drug delivery technologies that provide easier-to-use and more effective drug formulations. There are now ten approved products incorporating SkyePharma's technologies in the areas of oral, injectable, inhaled and topical delivery, supported by advanced solubilisation capabilities. For more information, visit http://www.skyepharma.com/. A wholly owned subsidiary of Endo Pharmaceuticals Holdings Inc. (NASDAQ: ENDP), Endo Pharmaceuticals is a fully integrated specialty pharmaceutical company with market leadership in pain management products. The company researches, develops, produces and markets a broad product offering of branded and generic pharmaceuticals, meeting the needs of healthcare professionals and consumers alike. More information, including this and past press releases of Endo Pharmaceuticals Holdings Inc., is available online at http://www.endo.com/. About DepoDur(TM) DepoDur(TM) is a single dose extended-release injectable formulation of morphine sulphate. DepoDur(TM) employs SkyePharma's proprietary DepoFoam(TM) technology and is supplied as a ready-to-use suspension. It is given as a single epidural injection before or during surgery and provides pain relief for up to 48 hours following surgery. There is no need for an in-dwelling catheter for continuous infusion, thereby overcoming a major drawback to the otherwise theoretically desirable epidural route of administration for opioid analgesics. DepoDur(TM) is designed for the control of pain after major surgery. SkyePharma and Endo expect that its main use will be in control of post- operative pain in hospitalised patients undergoing major surgical procedures requiring general or regional anaesthesia such as major abdominal surgery, orthopaedic surgery and caesarean section. Currently there are an estimated 6 million such procedures every year in the USA and 5 million in Europe. DepoDur(TM) is supplied in a 2 ml vial containing a 10 mg/ml suspension in sterile saline and is administered as a single dose epidural injection at the lumbar level prior to surgery (or after clamping of the umbilical cord during caesarean section). The recommended dose is 10 mg for caesarean section, 10-15 mg for lower abdominal surgery and 15 mg for major orthopaedic surgery of the lower extremities. Some patients may benefit from a dose of 20 mg. It should be appreciated that as with all opioids the incidence of serious adverse respiratory events is dose-related. Respiratory depression is the chief hazard of all opioid preparations and occurs more frequently in elderly or debilitated patients. For elderly patients (age >65 years), the low end of the dosing range for DepoDur(TM) is recommended together with vigilant peri-operative monitoring. On 16 September 2003 the FDA formally accepted for filing a New Drug Application ("NDA") for DepoDur(TM), which had been submitted on 18 July 2003. On 20 November 2003 SkyePharma submitted an application for DepoDur(TM) to the UK Medicines and Healthcare products Regulatory Agency ("MHRA"). After national approval in the UK, SkyePharma intends to seek approval in other European Union countries under the Mutual Recognition procedure. SkyePharma has licensed DepoDur(TM) to Endo for North America and to Medeus Pharma for Europe. SkyePharma has completed seven clinical trials of DepoDur(TM). The Phase IIb and Phase III clinical development programme for DepoDur(TM) involved four separate pain models and included more than 1000 patients. In the two Phase III trials, in hip surgery and lower abdominal surgery, DepoDur(TM) demonstrated extended dose-related analgesia and achieved its primary endpoint (superiority over study comparators in terms of total demand for opioid analgesics after surgery) with a high degree of statistical significance (p