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Alchemia Reports Preliminary Positive Efficacy Data From HyCAMP Phase II Trial

SYDNEY, Australia, April 26, 2007 /PRNewswire-FirstCall/ -- Australian drug development company Alchemia Limited today announced preliminary results from its randomised Phase II clinical trial in patients with metastatic colorectal cancer, where Alchemia's drug HyCAMP(TM) was compared to irinotecan which is considered to be a cornerstone drug for the treatment of colorectal cancer. This announcement is being made at a preliminary stage of the analysis in accordance with the ASX disclosure requirements once the company became aware of the results reported below.

Primary safety endpoint - Comparison of the incidence of late grade 3 or 4 diarrhoea in patients receiving HyCAMP(TM) versus irinotecan alone:

    -- not met due to lower than expected incidence of diarrhoea in the

       control arm


    Secondary safety endpoints:


    -- No major differences in overall adverse events between the two

       treatment arms


    Secondary efficacy endpoints:


    -- 38 of 41 (93%) HyCAMP(TM) patients compared to 28 of 35 (80%)

       irinotecan patients completed 2 cycles (p=0.099)


    -- 14 of 41 (34%) HyCAMP(TM) patients compared to 5 of 35 (14%) irinotecan

       patients completed the full 8 cycles (p=0.064)


    -- Patients on HyCAMP(TM) received a median of 6 cycles of therapy,

       compared to 2 for irinotecan alone (p=0.005)


    -- Median progression free survival for HyCAMP(TM) patients was 5.2

       months, compared to 2.4 months for the irinotecan arm (p=0.014).

The Phase II trial commenced in December 2004 and patient accrual closed on 30 June 2006. In the randomised trial, 80 patients with metastatic colorectal cancer who had previously failed treatment with the anti-cancer drug 5-fluoro uracil were eligible to receive up to eight cycles of chemotherapy in the form of irinotecan or HyCAMP(TM) intravenously. The primary endpoint of the trial was safety (incidence of Grade 3/4 diarrhoea) with secondary safety and efficacy endpoints such as disease control, progression free survival and overall survival.

The major findings from the preliminary analysis of trial data are as follows. The two arms of the study were very well balanced for known prognostic factors. Preliminary data regarding toxicity indicates no major differences between the two arms, with an overall impression that HyCAMP(TM) was associated with less cumulative toxicity because the HyCAMP(TM) arm received significantly more doses. The overall incidence of grade 3/4 diarrhoea was lower in this study (14%) than anticipated at the commencement of the trial, presumably reflecting improved medical management today of this side effect in patients, and thereby impeding any meaningful analysis of this endpoint. Patients on HyCAMP(TM) received a median of 6 cycles of therapy, compared to 2 for irinotecan alone (p=0.005). Median progression free survival for HyCAMP(TM) patients was 5.2 months, compared to 2.4 months for the irinotecan arm (p=0.014). Preliminary data indicates the proportion of patients exhibiting disease control (complete responses, partial responses or stable disease) in the HyCAMP(TM) arm was at least 40 % greater than that observed in the irinotecan arm.

Analysis of the trial data is ongoing and full results will be presented when available. This is expected by the end of May. However, from the data analysed to date, HyCAMP(TM) is able to deliver more cycles of therapy and this has translated into an improved disease control rate, and a statistically significant improvement in progression free survival. "The findings have far exceeded our expectations in that we did not expect to achieve a statistically significant improvement in efficacy from such a small number of patients" commented principal investigator Associate Professor Peter Gibbs. Alchemia CEO Dr Ramsdale said "we will be moving as quickly as possible to discuss our plans for future studies with the FDA. We are hopeful that these results will enable us to move forward to a pivotal phase III study earlier than originally anticipated."

These results are important not only for the development and approval path for HyCAMP(TM) itself but they provide validation of the technology platform. The HyACT(TM) platform is an extremely flexible formulation technology as it can be used with virtually any intravenously administered anti-cancer treatment. We have successfully completed Phase I clinical studies on HyACT(TM) formulations of two other chemotherapy drugs, doxorubicin and 5- flurouracil. Encouraging preclinical data has also been obtained on a number of other cytotoxics. More recently, we have demonstrated in preclinical studies that HyACT(TM) can also be used to significantly enhance the efficacy of newer targeted antibody therapies such as Avastin(TM) and Erbitux(TM) In the case of generic drugs or drugs close to patent expiry, the HyACT(TM) formulation may provide a means for companies to differentiate their products from other competitors in the market place, and thereby build product value.

HyCAMP(TM) and the proprietary formulation technology, HyACT(TM), were obtained following the successful acquisition of Melbourne based oncology company Meditech Research Limited in 2006. "The Phase II clinical results provide proof of concept for the HyACT(TM) platform. We expect this technology to build substantial value for shareholders, not only with HyCAMP(TM), but with other oncology drugs as well" Dr Ramsdale said.

Before HyCAMP(TM) can be marketed in the US, the drug needs to successfully complete a Phase III study, and receive marketing approval from the US FDA.

Alchemia wishes to acknowledge the commitment and thank the patients who volunteered to participate in this trial, and to acknowledge and thank the investigators, study research personnel and nursing staff at the 10 clinical sites across Australia who looked after the welfare of the patients and diligently collected the data for analysis in this trial.

    ENQUIRIES: Dr. Tracie Ramsdale

    Chief Executive Officer

    Alchemia Limited

    Tel: +61-7-3340-0200


    RELEASED BY:

    Ms Anna Whybird

    Phillips Group

    Tel: +61-7-3230-5000

About HyACT

HyACT(TM) is a proprietary delivery technology which utilises Hyaluronic acid (HA), to deliver and enhance the retention of anti-cancer drugs within tumours. The drug becomes entrapped in a matrix of HA which binds to HA receptors located on the tumour resulting in more of the drug being delivered to the tumour cells. In preclinical studies, the HyACT(TM) technology has demonstrated improved delivery of the drug to the tumour resulting in significantly reduced toxicity and increased efficacy and survival.

About Irinotecan

Irinotecan is widely used in the treatment of metastatic colorectal cancer, and is being evaluated in many other tumour types. Like most cytotoxics the use of irinotecan is restricted by its side effects, the most significant of which are diarrhoea and neutropenia, and limited activity in some patients. Sales of Pfizer's irinotecan (Camptosar(R) ) were US$903 million in 2006, and patent exclusivity for the drug expires in 2008 in the US and 2009 in the EU.

About HyCAMP(TM)

HyCAMP(TM) is a proprietary formulation of the anti-cancer drug irinotecan. Preclinical studies with HyCAMP(TM) demonstrated improved delivery of the drug to the tumour, resulting in increased efficacy and reduced toxicity. The phase II clinical trial was initiated to evaluate HyCAMP(TM) in patients with metastatic colorectal cancer.

CLINICAL APPENDIX

The following additional information is provided in accordance with the Code of Best Practice for ASX Reporting by Life Science Companies

    Trial Title        Randomised Phase II Trial of irinotecan with Hyaluronic

                       Acid (HyCAMP(TM)) versus irinotecan as treatment for

                       patients with metastatic colorectal cancer who have

                       failed 5-FU based chemotherapy


    Blinding Status    Open label, randomised


    Treatment Method   HyCAMP(TM) arm:

                       Irinotecan: 350mg/mm2 day 1 every 3 weeks or

                       300 mg/mm2 day 1 every 3 weeks for age 70-75

                       HA: 1000 mg/mm2 day 1 every 3 weeks


                       Irinotecan arm:

                       Irinotecan: 350mg/mm2 day 1 every 3 weeks or

                       300 mg/mm2 day 1 every 3 weeks for age 70-75


                       Duration of treatment: maximum of 8 cycles


                       Route of administration: intravenous


    No of subjects     80


    Key Subject Selection Criteria   Metastatic colorectal cancer

                                     Failure of previous fluorouracil

                                     chemotherapy, Adequate major organ

                                     function ECOG PS (performance score) 0-1.

                                     Age 18-75 years



    Trial Location                   10 sites in Australia


    Primary endpoint                 Comparison of the incidence of late grade

                                     3 or 4 diarrhoea in patients receiving

                                     HyCAMP(TM) versus irinotecan alone


    Main Secondary safety end points


    1. Incidence of grade 3 or 4 diarrhoea in cycle 1 or cycle 2

    2. Requirement for dose reduction for any cause after 2 cycles of therapy

    3. Requirement for dose reduction for any reason

    4. Overall incidence of grade 3 or 4 neutropenia

    5. Overall adverse events


    Main Secondary efficacy end points


    1. Number of patients completing 2 cycles of therapy

    2. Number of patients completing 8 cycles of therapy

    3. Median number of cycles delivered

    4. Disease Control Rate

    5. Median Progression Free Survival

    6. Median Overall Survival

    7. 50% or greater decline in CEA levels

    8. Time to treatment failure Study Results


    Study Results



    Patient demographics



                                 Control       HyCAMP(TM)      Overall

                                 (n = 35)       (n = 41)      (n = 76)


    Sex                  Male    21 (60.0)     24 (58.5)     45 (59.2)

                         Female  14 (40.0)     17 (41.5)     31 (40.8)


    Age (Years)          n             35            41            76

                         Median     63.11         62.30         62.67


    ECOG Status          0             16            19            45

                         1             19            22            31


    Prior oxaliplatin

     therapy             n             30            34            64



    Primary Endpoint

    1. Incidence of grade 3 or 4 diarrhoea in HyCAMP(TM) arm versus irinotecan

       arm.

       The overall incidence of Grade 3/4 diarrhoea (14%) was much lower than

       anticipated (30%) making analyses of this end point futile. There was

       no statistically significant difference in the incidence of grade 3 or

       4 diarrhea in the HyCAMP(TM) arm versus the irinotecan arm.


    Secondary safety endpoints

    1. Incidence of grade 3 or 4 diarrhoea in cycle 1 or cycle 2

       see comment above for primary end-point all but one case of diarrhoea

       occurred in Cycle 1


    2. Requirement for dose reduction for any cause after 2 cycles of therapy

       to be determined


    3. Requirement for dose reduction for any reason

       to be determined


    4. Overall incidence of grade 3 or 4 neutropenia

       to be determined


    5. Overall adverse events -

       no major differences between treatment arms


    Secondary Efficacy Endpoints

    1. Number of patients completing two cycles of therapy

       38 of 41 (93%) HyCAMP(TM) patients compared to 28 of 35 (80%)

       irinotecan patients completed 2 cycles (p=0.099)


    2. Number of patients receiving full 8 cycles

       14 of 41 (34%) HyCAMP(TM) patients compared to 5 of 35 (14%) irinotecan

       patients completed 8 cycles (p=0.064)


    3. Median number of cycles delivered

       Patients on HyCAMP(TM) received a median of 6 cycles of therapy

       compared to 2 for irinotecan alone (p=0.005).


    4. Disease control rate (Complete Response + Partial Response + Stable

       Disease)

       The proportion of patients exhibiting disease control was at least

       40% higher in the HyCAMP(TM) arm than the control (analysis partially

       complete)


    5. Median progression free survival

       Mean progression free survival was 5.2 months for HyCAMP(TM) vs 2.4

       months for the control arm (p=0.014).

Please refer to graph available via announcement on the Australian stock exchange (ASX).

    6. Median overall survival

       To be determined


    7. 50% or greater decline in CEA levels

       To be determined


    8. Time to treatment failure

       To be determined


    Principal Investigator

    Assoc. Prof Peter Gibbs, Royal Melbourne Hospital and Western Hospital

CONTACT: Dr. Tracie Ramsdale, Chief Executive Officer, Alchemia Limited,+61-7-3340-0200; Ms Anna Whybird, Phillips Group, +61-7-3230-5000, forAlchemia Limited

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Posted: April 2007

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