Lodotra(R) (Modified-Release Prednisone) Now Launching Across Europe for Treatment of Rheumatoid Arthritis and Associated Morning Stiffness

Innovative Modified-Release System Offers Hope to Those Whose Quality of Life is Significantly Impacted by Morning Stiffness

CAMBRIDGE, England, June 18, 2010 - Mundipharma announced today that 13 European countries to date have
received approval of Lodotra(R) (modified-release prednisone), a new
treatment for rheumatoid arthritis (RA) which offers the benefits of
conventional prednisone, with the added advantage of a clinical reduction in
morning stiffness, a barrier to the morning functioning of people with RA.

A complexity of symptoms including physical dysfunction, stiffness and
pain in joints (particularly affecting the hands) first thing in the morning
can be a barrier to normal morning function. Pain and stiffness in the
morning have been linked with increased concentrations of inflammatory
chemicals, known as cytokines that circulate in the blood(1). Interleukin-6
(IL-6) is one such cytokine which peaks in the early morning hours,
manifesting itself as inflammation, pain and stiffness in joints upon waking,
affecting ability to work and impacting on quality of life(1,2,3.)

Taken at 10.00pm, Lodotra utilises a unique modified-release mechanism to
begin releasing low-dose prednisone about four hours after ingestion, at a
time in the early morning when inflammation builds up and damage occurs1.
Maximum levels of prednisone in the blood are reached six hours after
ingestion, at the optimum time when levels of pro-inflammatory cytokines such
as IL-6 are at their natural peak, reducing the impact of joint stiffness for
people with RA in the first few hours after waking(1,4,5,6). Conventional
prednisone taken in the morning does not adequately control symptoms of pain
and stiffness(1).

The need for a new treatment option for those who suffer from morning
stiffness is supported by results from new research involving people with RA
and physicians, carried out by Ipsos MORI and commissioned by Mundipharma
across 11 European countries. Almost three quarters (74%) of people across
Europe living with pain and stiffness in the morning as a result of their RA
say that they are either unemployed, early retired or on sick leave as a
result of RA and over half (58%) say they are frustrated emotionally because
they find it more difficult to do everyday tasks(7). Nearly two thirds (60%)
of people with RA say that pain and stiffness in the morning controls their
lives(7).

Maurizio Cutolo, Professor of Rheumatology, Director Research Laboratory
and Academic Unit of Rheumatology, University of Genova says: "The stiffness
and pain experienced in the morning by people with RA appear to have a direct
impact on quality of life, particularly in relation to work. 74% of people
with RA questioned said that these symptoms have a significant impact on
their work, with over a quarter confessing that the pain and stiffness they
experience in the morning has been a direct factor in slowing their career
progression - one in seven had to change profession(7). There is therefore a
clear need for new treatment options to specifically address the issue of
morning stiffness."

Over a quarter (29%) of those with RA questioned state that it can take
between one and a half and three hours before they are even able to start
their day due to pain and stiffness in the morning resulting from their RA7.
This is in direct contrast to the opinion of the majority of rheumatologists,
62% of whom believe pain and stiffness in the morning only lasts between 30
minutes to one hour8.

Describing her experience with rheumatoid arthritis, Danielle Leys from
Belgium says: "As my rheumatoid arthritis has progressed I find it very
difficult to carry out tasks in the morning. The hardest thing to accept is
not being able to take my grandchildren to school any more - I'm not even
able to carry them in my arms and I find that very upsetting. I used to work
as a typist but because of the stiffness in my hands, I had to leave my job.
My biggest wish is that I could do everything myself without the help of
others - it would just be nice to get my old life back."

Approval of Lodotra is supported by clinical data which showed that after
12 weeks of treatment, evening administration of Lodotra resulted in a
significant decrease in duration of morning stiffness of the joints than was
recorded after morning administration of conventional prednisone(1).

A total of 288 patients with active rheumatoid arthritis took part in the
Circadian Administration of Prednisone in Rheumatoid Arthritis (CAPRA-1)
trial. Participants were randomly assigned to 12 weeks of double-blind
treatment, with either modified-release prednisone (Lodotra) or immediate
release (standard) prednisone1. At the end of the treatment, those who were
administered Lodotra achieved a significantly higher mean relative change in
duration of morning stiffness of the joints from baseline than with
immediate-release prednisone (-22.7% vs -0.4%; [95% CI 0.49-44.30];
p=0.045)(1). Results also showed Lodotra significantly reduced levels of IL-6
serum concentrations after three months, but conventional prednisone had no
effect on IL-6 levels1. In addition to reducing morning stiffness, this study
showed that therapy with Lodotra was well tolerated and had a safety profile
similar to the same dose of conventional prednisone(1).

In another Phase III trial (CAPRA-2) treatment with Lodotra in
combination with a disease-modifying anti-rheumatic drug (DMARD) resulted in
a clinically significant improvement in ACR 20 response rate, the primary
endpoint of the trial, compared to DMARD alone. Improvements in both pain and
morning stiffness - barriers to morning function - were demonstrated(9). In
this trial, Lodotra was also found to be well tolerated(10).

Notes to Editors:

About Lodotra

Lodotra is licensed for the treatment of rheumatoid arthritis and
associated morning stiffness. It is administered in the form of a specially
formulated tablet which utilises modified-release technology. The active drug
is contained within an outer tablet layer which acts as a barrier between the
gastrointestinal fluids in the stomach and the active core. Water in the
digestive tract causes the outer layer to break and release prednisone from
the core. The innovative technology allows the drug to be delivered at a
pre-determined release rate, which in this case is four hours after
ingestion.

Lodotra was first launched in Germany in April 2009, and has been
approved for the treatment of RA and associated morning stiffness in a
further 12 countries including Austria, Belgium, Denmark, Finland, France,
Luxembourg, the Netherlands, Norway, Poland, Portugal, Sweden and the United
Kingdom. Studies are planned to investigate the use of modified-release
prednisone in other conditions in which IL-6 plays a role such as severe
asthma and polymyalgia rheumatica.

For more information: www.lodotra.com

(R) Lodotra is a registered trade mark.

About Mundipharma

The Mundipharma/Napp/Norpharma independent associated companies,
including Mundipharma, Purdue and Napp, are privately owned companies and
joint ventures covering the world's pharmaceutical markets. The companies
worldwide are dedicated to bringing to patients with severe and debilitating
diseases the benefits of novel treatment options in fields such as rheumatoid
arthritis, severe pain, haemato-oncology and respiratory disease.

For more information: www.mundipharma.co.uk

About Horizon Pharma

Horizon Pharma, Inc., the licensor of Lodotra, is a late-stage
biopharmaceutical company focused on the development and commercialization of
innovative medicines for pain-related diseases and chronic inflammation.

For more information: www.horizonpharma.com.

About the research

This research was carried out across 550 rheumatologists and 750 patients
aged between 18 and 75 from 11 countries across Europe: the United Kingdom,
Spain, France, Italy, Sweden, Denmark, The Netherlands, Norway, Belgium,
Finland and Poland. All patients surveyed had been diagnosed with RA for at
least 6 months and all suffer from impaired morning function at least 3 times
a week.

References

1. Buttgereit F, Doering G, Schaeffler A et al. Efficacy of
modified-release versus standard prednisone to reduce duration of morning
stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind,
randomised controlled trial. Lancet 2008; 371: 205-214

2. Westhoff G, Buttgereit F, Gromnica-Ihle E et al. Morning stiffness and
its influence on early retirement in patients with recent onset rheumatoid
arthritis. Rheumatology 2008; 47(7): 980-984

3. Kirwan JR, Clarke L, Hunt LP et al. Effect of novel therapeutic
glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid
arthritis. Ann NY Acad Sci 2010; 1193: 127-133

4. Cutolo M, Straub RH and Buttgereit F. Circadian rhythms of nocturnal
hormones in rheumatoid arthritis: translation from bench to bedside. Ann
Rheum Dis 2008; 67: 905-908

5. Cutolo M et al. Circadian rhythms in RA. Ann Rheum Dis 2003; 62:
593-596

6. Cutolo M et al. Circadian melatonin and cortisol levels in rheumatoid
arthritis patients in winter time: a north and south Europe comparison. Ann
Rheum Dis 2005; 64(2): 212-216

7. Ipsos MORI RA patient study May 2010. Participants: 750 adults

This research was commissioned by Mundipharma International

8. Ipsos MORI Rheumatologist study May 2010. Participants: 550
rheumatologists

This research was commissioned by Mundipharma International

9. Buttgereit F et al. CAPRA-2 efficacy data presented at EULAR 2010

10. Buttgereit F et al. CAPRA-2 safety data presented at EULAR 2010

For further information please contact: Mani Reel, mani.reel at redconsultancy.com , +44-207-025-6584; Ellie Moffat, eleanor.moffat at redconsultancy.com , +44-207-025-6584.