SYDNEY, Australia, April 26 /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
Alchemia Limited
CONTACT: Dr. Tracie Ramsdale, Chief Executive Officer, Alchemia Limited,+61-7-3340-0200; Ms Anna Whybird, Phillips Group, +61-7-3230-5000, forAlchemia Limited
