Morphine Liposomal--SkyePharma: C 0401, D 0401, morphine--DepoFoam, SKY 0401.

Abstract

The SkyePharma PLC subsidiary SkyePharma Inc. (formerly DepoTech) is developing a sustained-release formulation of morphine sulphate [DepoMorphine, C 0401, D 0401, SKY 0401] using its DepoFoam proprietary drug delivery technology. It is intended for epidural administration in the treatment of acute postoperative pain. DepoFoam consists of microscopic spherical particles with internal aqueous chambers separated by lipid membranes containing the encapsulated drug. DepoFoam particles are synthetic replicas of natural lipids that are biodegradable and biocompatible. DepoFoam can be administered subcutaneously, intramuscularly and intrathecally. In December 2002, SkyePharma and Endo Pharmaceuticals signed a development and commercialisation agreement providing Endo Pharmaceuticals with exclusive marketing and distribution rights in the US and Canada for Depomorphine and another product, Propofol IDD-D trade mark, with options for other development products. Under the terms of the agreement, SkyePharma will receive an upfront payment and may receive further milestone payments. Skye-Pharma will also receive a share of each product's sales revenue. SkyePharma is responsible for clinical development towards the US FDA approval and for product manufacture and associated costs. Following the approval, SkyePharma will as act as a supplier, while Endo will market each product in the US and Canada. SkyePharma has received 30 million US dollars from Paul Capital Partners, a US private equity group, to develop DepoMorphine. This capital will enable SkyePharma to fund phase III clinical trials without raising extra funds. Paul Capital will have rights to 15% of any revenues from DepoMorphine until 2014, and also receive some royalties on three other SkyePharma products. However, if DepoMorphine fails in clinical trials or is declined for registration, Paul Capital will not be compensated for the investment. SkyePharma expect to conclude a European license by the end of 2003, and are also in discussions with potential Japanese licensees. In July 2003, SkyePharma submitted an NDA to the US FDA for DepoMorphine in the treatment of moderate to severe postoperative pain. The FDA accepted the filing in September, triggering a milestone payment to Skye-Pharma. Positive results from two phase III trials in 750 patients after hip surgery and lower abdominal surgery released in June 2003 report that DepoMorphine is effective in providing sustained dose-related analgesia. DepoMorphine demonstrated sustained dose-related analgesia and achieved its primary endpoint and also statistical significance on several secondary endpoints such as patient perception of pain intensity and adequacy of pain relief. The Financial Times in January 2001 reported that analysts have forecast DepoMorphine to reach peak sales of more than 200 million US dollars. In April 2001, the Wall Street Journal quoted the CEO of SkyePharma predicting that DepoMorphine has the potential to reach combined annual sales, in the US and Europe, of approximately 350 million US dollars.