LONDON, Jul 21, 2003 /PRNewswire-FirstCall via COMTEX/ -- SkyePharma PLC (Nasdaq: SKYE; LSE: SKP) announced today that on 18 July it submitted a New Drug Application to the US Food & Drug Administration ("FDA") for DepoMorphine(TM), SkyePharma's novel sustained-release injectable formulation of morphine for control of moderate-to-severe post-operative pain. DepoMorphine(TM) was licensed to Endo Pharmaceuticals Inc. ("Endo", Nasdaq: ENDP) for North America at the end of 2002. SkyePharma will receive an unspecified milestone payment from Endo on acceptance of the DepoMorphine(TM) submission by the FDA.

SkyePharma's Chief Executive Michael Ashton said, "DepoMorphine(TM) is currently our most important pipeline product. Having taken the decision to undertake full clinical development ourselves, we are extremely proud to have delivered on our promise to complete the clinical studies for DepoMorphine(TM) and to file it with the FDA on time. Our clinical trials show that DepoMorphine(TM) has great potential to improve the treatment of pain after surgery. There is widespread recognition that pain relief is an under-served market and current approaches to control of post-operative pain leave much to be desired."

DepoMorphine(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 highly effective pain relief for 48 hours following surgery. There is no need for an indwelling catheter for continuous infusion, which overcomes a major drawback to the epidural route of administration for opioids.

DepoMorphine(TM) is designed for the control of moderate-to-severe post-operative pain. SkyePharma expects that its main use will be in control of post-operative pain in hospitalised patients undergoing surgical procedures requiring general or local anaesthesia such as major abdominal surgery, orthopaedic surgery and caesarean section. Currently there are an estimated 7 million such procedures every year in the USA and 5 million in Europe.

SkyePharma has completed seven clinical trials of DepoMorphine(TM). The Phase IIb and Phase III clinical development programme for DepoMorphine(TM) involved four separate pain models and included nearly 1000 patients. In the two Phase III trials, in hip surgery and lower abdominal surgery, DepoMorphine(TM) demonstrated sustained 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<0.0001 and p=0.0003, respectively). DepoMorphine(TM) also achieved statistical significance on several secondary endpoints such as patient perception of pain intensity and adequacy of pain relief.

In two related Phase IIb trials, DepoMorphine(TM) was significantly better than study comparators in the caesarean section study (p=0.0209) and approached statistical significance in the knee arthroplasty study (p=0.0902), which used a novel endpoint: time-weighted pain intensity recall score over 48 hours. DepoMorphine(TM) achieved a high degree of statistical significance in total demand for opioid analgesics after surgery (p=0.001), a secondary endpoint in this trial but the primary endpoint in the three other studies. In all four of these studies the safety profile of DepoMorphine(TM) was typical for an epidural opioid agent.

SkyePharma plans to file DepoMorphine(TM) with the European Agency for the Evaluation of Medicinal Products (EMEA) in the autumn. SkyePharma expects to announce the appointment of licensees for DepoMorphine(TM) in Europe and other non-US territories later this year.

About SkyePharma

SkyePharma PLC uses its world-leading drug delivery technology to develop easier-to-use and more effective formulations of drugs. The majority of challenges faced in the formulation and delivery of drugs can be addressed by one of the Company's proprietary technologies in the areas of oral, injectable, inhaled and topical delivery, supported by advanced solubilisation capabilities. For more information, visit http://www.skyepharma.com.

About DepoFoam(TM)

DepoFoam(TM) is SkyePharma's proprietary sustained-release injectable delivery technology. This is fully commercialised and approved by regulatory agencies in both the USA and Europe. DepoFoam(TM) consists of tiny lipid-based particles containing discrete water-filled chambers dispersed through the lipid matrix. The particles are 10-30 microns in diameter and are suspended in saline. The suspension resembles skimmed milk and can be injected through a fine needle. The water-filled chambers containing active drug account for most of the weight of the particles. The lipids are naturally occurring substances (or close analogues) such as phospholipids and triglycerides. The small amount of lipid is cleared rapidly in the body as the particles deliver their drug payload over a period that can be modified from 1 to 30 days. For example in DepoCyt(R)/DepoCyte(R) the circulating half-life of the drug cytarabine is increased from 3.4 hours to 141 hours.

About post-operative pain

After a major surgical operation, the level of pain is usually very high for the first one to two days but the intensity of pain gradually subsides and by the end of the second day pain can normally be controlled with oral analgesics. For the immediate post-operative period, opioid analgesics like morphine (used alone or in combination with other non-opioid analgesics) are likely to remain the "gold standard" for relief of severe acute pain. However the relatively short duration of pain relief with opioids means that they require either continuous infusion or patient-controlled analgesia ("PCA") in which a pump delivers a series of doses of a short-acting opioid analgesic in response to the patient pressing a button (under computer control to prevent over-dosing). Both of these approaches require the patient to have an in-dwelling epidural or intravenous catheter. Such catheters can fall out or interfere with patient mobility and are a potential source of infections. Epidural catheters are also contra-indicated with concomitant use of anticoagulants because of the risk of bleeding in the spinal column that can potentially result in paralysis. There is a growing trend to routine use of anticoagulants in patients undergoing orthopaedic surgery in order to prevent blood clots.

Except for the historical information herein, the matters discussed in this news release include forward-looking statements that may involve a number of risks and uncertainties. Actual results may vary significantly based upon a number of factors, which are described in SkyePharma's 20-F and other documents on file with the SEC. These include without limitation risks in obtaining and maintaining regulatory approval for existing, new or expanded indications for its products, other regulatory risks, risks relating to SkyePharma's ability to manufacture pharmaceutical products on a large scale, risks that customer inventory will be greater than previously thought, risks concerning SkyePharma's ability to manage growth, market a pharmaceutical product on a large scale and integrate and manage an internal sales and marketing organization and maintain or expand sales and market share for its products, risks relating to the ability to ensure regulatory compliance, risks related to the research, development and regulatory approval of new pharmaceutical products, risks related to research and development costs and capabilities, market acceptance of and continuing demand for SkyePharma's products and the impact of increased competition, risks associated with anticipated top and bottom line growth and the possibility that upside potential will not be achieved, competitive products and pricing, and risks associated with the ownership and use of intellectual property rights. SkyePharma undertakes no obligation to revise or update any such forward-looking statement to reflect events or circumstances after the date of this release.

SOURCE SkyePharma PLC

Michael Ashton, Chief Executive Officer, or Peter Laing,
Director of Corporate Communications, +44-207-491-1777, or Sandra Haughton, US
Investor Relations, +1-212-753-5780, all of SkyePharma PLC; or Tim Anderson or
Nicola How, +44-207-466-5000, both of Buchanan Communications

http://www.skyepharma.com