SkyePharma: NDA submission in US for Lodotra in RA

SkyePharma Announces Submission of New Drug Application in the United States for Lodotra® for the treatment of Rheumatoid Arthritis

LONDON, UK, 28 September, 2011 - SkyePharma PLC (LSE: SKP) today announces that its licensee, Horizon Pharma, Inc ("Horizon"), has submitted a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for Lodotra® for the treatment of active rheumatoid arthritis (RA).

Lodotra® utilises SkyePharma's Geoclock™ technology to provide a proprietary delayed-release formulation of low-dose prednisone. Prednisone is currently FDA-approved for RA and commonly used to inhibit the production of various pro-inflammatory cytokines, which are proteins associated with joint inflammation in RA.

SkyePharma is entitled to a low-mid single digit percentage royalty on net sales of Lodotra® in North America and a mid-single digit percentage royalty elsewhere. Lodotra® is manufactured at the Lyon Manufacturing Facility recently leased by the Group to Aenova.

The Lodotra® NDA submission was primarily based on results from the Circadian Administration of Prednisone in RA (CAPRA-2) trial, a pivotal, 12-week, double-blind, placebo-controlled Phase 3 trial involving 350 RA patients. Both treatment groups in the trial continued to receive standard of care RA treatment with a disease-modifying anti-rheumatic drug (DMARD). Horizon has announced that the results from CAPRA-2 demonstrated:

·; A statistically significant improvement in American College of Rheumatology 20 (ACR20) response criteria, the primary study endpoint, for patients who were treated with Lodotra® compared with the placebo group (48.5% vs. 28.6%; p-value = 0.0002)

·; A statistically significant improvement in ACR50 response compared with placebo (22.7% vs. 9.2%; p-value = 0.0027) and an improvement in the more stringent ACR70 response criteria (7.0% vs. 2.5%; p-value = 0.0955)

·; A statistically significant reduction in morning stiffness compared with patients in the placebo group (56.5% vs. 33.3%; p-value = 0.0008)

Additional data in the NDA submission included results from the CAPRA-1 study, which was a 12 week, double-blind, placebo-controlled study in Europe evaluating 288 RA patients. CAPRA-1 compared the night-time administration of Lodotra® with the morning administration of immediate release prednisone at the same individual dose (average dose of 6.7 mg). Horizon has announced that the results from CAPRA-1 demonstrated:

·; A statistically significant reduction in morning stiffness compared with patients in the immediate release group, the primary outcome of the trial (22.7% for Lodotra® compared with 0.4% for immediate release prednisone (p-value = 0.045))

·; Patients treated with Lodotra® had a reduction in IL-6 levels of approximately 29% (relative median change), which was statistically significant, while corresponding IL-6 levels following treatment with immediate release prednisone remained constant

Following the 12-week CAPRA-1 study, patients were followed in a nine-month, open-label extension study, which included 249 RA patients, 219 of whom completed the extension study. Results showed that patients who continued treatment with Lodotra® experienced a 55% reduction in the duration of morning stiffness. Further, patients newly assigned to Lodotra® exhibited a 45% reduction in the duration of morning stiffness over the nine-month course of this extension study. These patients also experienced a 50% median reduction in IL-6 levels that also corresponded to improvements in the duration of morning stiffness following daily administration of Lodotra®.

A Phase 3 clinical trial of Lodotra® for the treatment of polymyalgia rheumatica (PMR) is being planned by Horizon. This indication is not included in the NDA.

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About SkyePharma PLC

Using its proprietary drug delivery technologies, SkyePharma develops new formulations of known molecules to provide a clinical advantage and life-cycle extension. The Group has twelve approved products in the areas of oral, inhalation and topical delivery. The Group's products are marketed throughout the world by leading pharmaceutical companies. For more information, visit www.skyepharma.com.

About Rheumatoid Arthritis ("RA")

RA is a chronic disease that causes pain, stiffness and swelling, primarily in the joints. RA affects approximately 1.8 million people in the United States and is not associated with factors such as ageing. RA occurs when the body's immune system malfunctions, attacking healthy tissue and causing inflammation, which leads to pain and swelling in the joints, and may eventually cause permanent joint damage and painful disability. The primary symptoms of RA include progressive immobility and pain, especially in the morning, with long-term sufferers experiencing continual joint destruction for the remainder of their lives.

About Lodotra®

Lodotra®, is a novel programmed-release formulation of low dose prednisone, utilising SkyePharma's proprietary Geoclock™ technology and developed in collaboration with Horizon Pharma, Inc ("Horizon"). It was approved in Europe in March 2009, under the European decentralised procedure, for the treatment of moderate to severe active rheumatoid arthritis in adults particularly when accompanied by related morning stiffness. It was launched in Germany in April 2009 and in Italy in January 2011. Horizon has licensed to Mundipharma the distribution rights for Lodotra® in Europe as well as in Australia, China, Hong Kong, Indonesia, Korea, Malaysia, New Zealand, Philippines, Singapore, South Africa, Taiwan, Thailand and Vietnam.