AZM Alizyme

    RNS Number : 7683Z
  Alizyme PLC
  24 July 2008
   

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 For immediate release  24 July 2008

    ALIZYME PLC

    ALIZYME ANNOUNCES HEADLINE RESULTS FROM ITS EUROPEAN PHASE III CLINICAL TRIAL OF COLAL-PRED� IN PATIENTS WITH MODERATE TO SEVERE
ULCERATIVE COLITIS

    Cambridge UK, 24 July 2008: Alizyme plc (LSE: AZM) ("Alizyme") today announces headline results of its European Phase III clinical trial
of COLAL-PRED� in patients with moderate to severe ulcerative colitis.

    Highlights

    *     Results indicate safe treatment for acute ulcerative colitis
    *     COLAL-PRED� showed significantly improved risk*benefit profile compared to conventional prednisolone
    *     Non-inferiority of efficacy of COLAL-PRED� to conventional prednisolone in terms of DAI at 8 weeks was not shown
    *     COLAL-PRED� showed equivalent efficacy in terms of SCCAI compared to conventional prednisolone after 8 weeks' dosing, and at the
12 week follow-up visit
    *     Optimal dose shown to be 40 mg of COLAL-PRED�
    *     Results indicate further potential for COLAL-PRED� in the maintenance of remission of ulcerative colitis
    *     Delay to submission of MAA pending discussions with partners and regulatory advisors


    Ulcerative colitis is a chronic relapsing inflammatory disease of the colon for which there is an unmet medical need for a therapy that
is both effective and safe. The 'gold standard' in terms of efficacy is conventional oral prednisolone. However, this has significant
adverse effects that limit its clinical use and restrict the duration for which it can be safely administered. COLAL-PRED� is the
combination of Alizyme's proprietary colonic drug delivery system, COLAL�, and prednisolone metasulfobenzoate sodium ("PMSBS"), a form of
prednisolone approved in Europe for the treatment of acute ulcerative colitis.

    The European Phase III trial was designed to demonstrate that in individual patients, COLAL-PRED� was both an effective, and a safe and
well tolerated treatment for ulcerative colitis, without the debilitating side-effects associated with conventional prednisolone. The study
was a double blind comparison of COLAL-PRED� capsules and conventional prednisolone tablets in patients with moderate to severe ulcerative
colitis.

    COLAL-PRED� (40 mg, 60 mg or 80 mg once daily ("o.d.")), administered for 8 weeks, was compared with conventional prednisolone. The
conventional prednisolone dosing regimen was 40 mg o.d. for 2 weeks, followed by a tapering regimen (to allow recovery from adrenal
suppression) that reached 0mg by Week 8. 

    The study had two co*primary endpoints:

    *     Safety Response
Superiority compared to conventional prednisolone in the proportion of patients who were Safety Responders (patients whose early morning
plasma cortisol was >150 nmol/l at Week 4 and at Week 8). 

    *     Efficacy Response
Non-inferiority compared to conventional prednisolone in the proportion of patients who were Efficacy Responders (patients who showed a
reduction of at least 3 points in their Disease Activity Index ("DAI") score at Week 8 (or time of withdrawal) compared to baseline). The
required non-inferiority margin was 15%.

    The key secondary endpoint that addressed the Target Product Profile was:

    *     Treatment Response
    Superiority compared to conventional prednisolone in the proportion of patients who were Treatment Responders (individual patients who
were both Efficacy Responders and Safety Responders).
    Other efficacy endpoints included change in Simple Clinical Colitis Activity Index ("SCCAI") score.

    Results
    799 patients were randomised; approximately 200 per treatment group. Of these, 543 (68%) completed study medication (65% to 67% in the
COLAL-PRED� groups and 74% in the prednisolone group). The mean initial DAI score was 8.1. Of the patients randomised, 40% had an initial
DAI score of *9.

    The Efficacy Responder rate in the COLAL-PRED� arms (approximately 56%) was about 18% lower than that in the prednisolone arm (74%).
Thus non-inferiority of efficacy of COLAL-PRED� to conventional prednisolone was not shown.

    The reduction in mean SCCAI in the COLAL-PRED� treatment groups was equivalent to that in the prednisolone treated group at Week 8
(reduction of 2.32 points and 2.42 points respectively in comparison with baseline) and at Week 12 (reduction of 3.06 points and 2.75 points
respectively).

    Early morning plasma cortisol was unchanged in the COLAL-PRED� treatment groups throughout the study, while there was a clinically
significant reduction of 170 nmol/l in the prednisolone group at Week 4. 

    The incidence of typical steroid-related adverse events was significantly lower in the COLAL-PRED� groups compared to the prednisolone
group. Cushingoid syndrome was reported by 5.3% patients in the prednisolone group compared to 0.0% to 1.0% in the COLAL*PRED� treated
patients, 4.8% of patients in the prednisolone group reported insomnia compared to 1.0% to 1.5% in the COLAL*PRED� groups, and 4.8% of
prednisolone patients reported acne compared to 0.0% to 1.5% of the COLAL*PRED� patients.

    Although non-inferiority of efficacy of COLAL-PRED� to conventional prednisolone was not shown, COLAL-PRED� was statistically superior
to prednisolone in the proportion of patients who were Treatment Responders, i.e. were both Efficacy and Safety Responders, thereby meeting
the key secondary endpoint with respect to addressing the Target Product Profile. 

    The results of the study support the product profile for COLAL*PRED� of safety as well as efficacy in individual patients. The excellent
safety profile, particularly the absence of an effect on plasma cortisol, also supports the long term administration of COLAL-PRED� for
maintenance of remission.

    There was no clinically relevant difference in response in terms of efficacy, safety and tolerability across the three COLAL*PRED�
treatment groups (40 mg, 60 mg or 80 mg o.d.), supporting a dose recommendation of 40 mg o.d.


    Commenting on the results, Prof. CJ Hawkey, Chief Coordinating Investigator, said:

    "These results indicate COLAL-PRED� to be a safe treatment for acute ulcerative colitis with fewer adverse effects than conventional
prednisolone and support further development of COLAL-PRED� for maintenance of remission."


    Commenting on today's announcement, Tim McCarthy, Alizyme's Chief Executive Officer said:

    "We are pleased to report that the headline results of this study indicate that COLAL-PRED� is a safe steroid in the treatment of
ulcerative colitis. The headline results also indicate that this product has potential for maintenance of remission of ulcerative colitis.
We will continue to analyse the results and, in conjunction with our partners and regulatory advisors, establish the optimum way forward in
commercialising this product."




    For further information, please contact:

 Alizyme plc                Tel: + 44 (0) 1223 896000 
 Tim McCarthy, Chief
 Executive Officer
 David Campbell, Finance
 Director 

 UK/Europe Enquiries
 Buchanan Communications    Tel: + 44 (0) 20 7466 5000 
 Lisa Baderoon                Tel: + 44 (0) 7721 413496



 US Enquiries
 Trout Group
 Tim Ryan
 Lee Stern                      Tel: + 1 (646) 378 2924
                                Tel: + 1 (646) 378 2922


    Further information on Alizyme can be found on the Company's website: www.alizyme.com


    Notes to editor

    Alizyme plc
    Alizyme is a speciality biopharmaceutical development company, focused on the therapeutic areas of metabolic disorders, gastrointestinal
disorders and cancer supportive care. In addition to COLAL-PRED� it is developing cetilistat for the treatment and management of obesity and
related diseases, such as type 2 diabetes and ATL-104 for mucositis, a side effect of cancer therapy.


    Ulcerative colitis
    Ulcerative colitis is an inflammatory disease of the colon that causes symptoms such as abdominal pain, bleeding, cramping, fatigue and
diarrhoea. These conditions are characterised by episodes of acute flare of the inflammation, followed by periods of remission. In severe
cases, surgery may be required to remove the diseased tissue.

    The ulcerative colitis market is currently dominated by anti-inflammatory steroids and 5*ASA products, which have safety and/or efficacy
issues. Currently around 2 million people in the major pharmaceutical territories around the world suffer from ulcerative colitis with
projected sales of COLAL-PRED� in these territories in excess of US$250 million per annum. 


    COLAL-PRED�
    COLAL-PRED� is a proprietary gastrointestinal product developed by Alizyme for the treatment of ulcerative colitis. It is the
combination of Alizyme's proprietary colonic drug delivery system, COLAL�, and a prednisolone ester, prednisolone metasulfobenzoate sodium
("PMSBS"), a steroid approved in Europe. 

    COLAL*PRED� has a coating that is broken down only in the colon, by locally occurring bacteria. This leads to topical delivery of PMSBS
to the colon, rather than systemic delivery.


    COLAL-PRED� partnerships
    In November 2007, Alizyme granted Prometheus Laboratories Inc ("Prometheus") an exclusive licence to develop and market COLAL-PRED� in
North America. Prometheus will be primarily responsible for clinical development costs in North America and has commenced Phase II
development.

    In December 2007, Alizyme entered into an agreement with TSD Japan Inc ("TSD") for the co-development and commercialisation of
COLAL-PRED� in Japan. TSD is scheduled to commence Phase I development of COLAL-PRED� later in 2008.

    In June 2008, Alizyme granted Norgine BV ("Norgine") an exclusive licence to develop and market COLAL-PRED� in Europe, South Africa, New
Zealand and Australia. Norgine will be responsible for commercialisation.

    COLAL�
    COLAL� is a drug delivery technology that enables drugs to be taken orally and then be specifically released when the preparation
reaches the colon. Achieving colonic release with conventional oral dosage forms has proved difficult because of the variation between
individuals in transit times and conditions within the gastrointestinal tract. COLAL� overcomes this difficulty by covering small pellets
containing the drug with a coating of ethylcellulose and a specific form of amylose (derived from starch). This coating prevents drug
release in the stomach and small intestine. When the pellets reach the colon the amylose in the coating is broken down by bacterial enzymes
and the drug is released.
        

    (Note: COLAL� and COLAL-PRED� are registered trademarks of Alizyme Therapeutics Limited)


    The identification of compounds for successful research, their progress through development and the obtaining of regulatory approvals or
authorisations before marketing, manufacture and/or distribution of products is not certain or a formality.

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