LONDON, Oct. 17, 2005 (PRIMEZONE) -- Cancer drug developer Antisoma (LSE:ASM) today announces preliminary findings from an ongoing phase II trial of AS1404 in lung cancer. With initial data available from 47 of the 71 patients enrolled, those receiving AS1404 in addition to chemotherapy showed a higher frequency of tumour responses (43.5% vs 33.3%) and a lower frequency of progressive disease (8.7% vs 33.3%) than those receiving chemotherapy alone. Details are provided below. To date, all safety findings in the AS1404 arm of the trial have been consistent with those observed with standard chemotherapy treatment.
The lung cancer study is a multi-centre, randomised, controlled trial in patients being treated for the first time for locally advanced or metastatic non-small cell lung cancer. Enrollment was completed in August 2005, and the trial has included patients with both squamous and non-squamous lung cancers. Follow up of patients is continuing and Antisoma plans to present further data at medical congresses. These will include the final investigator-determined response rates, independently validated response rates and data on time to disease progression and survival. Disease progression data are expected during the first half of 2006.
AS1404 belongs to a class of drugs called vascular disrupting agents. These drugs selectively attack tumour blood vessels, giving them broad potential against solid cancers, which depend on their blood supply to survive and grow. Antisoma's lung cancer study is the first controlled trial of a vascular disrupting agent to report evidence of anti-cancer activity.
Dr Mark McKeage of the University of Auckland, New Zealand, one of the Principal Investigators in the study, said: "These early data are fascinating and very encouraging."
AS1404 is included in Antisoma's strategic oncology alliance with Roche. Robin Breckenridge, Global Head, Pharma Partnering Operations at Roche said: "Vascular disrupting agents represent an interesting novel approach to cancer treatment. We will follow with great interest as further data emerge from the AS1404 trials."
Antisoma's CEO Glyn Edwards said: "Lung cancer is a terrible disease that affects a huge number of patients worldwide and there is a desperate need to improve on currently available therapies. It is very exciting to see the initial clinical data on AS1404 and we look forward eagerly to further results from the lung cancer study and data from our other phase II trials of AS1404 in prostate and ovarian cancers."
Details of the lung cancer trial and the findings available to date The AS1404 lung cancer study is a randomised, controlled, phase II trial being conducted at hospitals in France, Germany, Australia and New Zealand. Half of the patients in the study are receiving AS1404 plus chemotherapy (carboplatin and paclitaxel) while the other half are receiving chemotherapy alone. Endpoints in the study are response rates (the percentage of patients with a complete or partial response, as described below), time to disease progression, median survival and one-year survival.
The table below shows the tumour response outcomes reported by investigators for the first 47 patients treated in the trial. Tumour response outcomes relate to the impact of treatment on the growth of tumours.
Tumour response AS1404 + chemotherapy Chemotherapy alone
outcome
(See notes below)
Number % Number %
Complete response 0 0 0 0
Partial response 10 43.5 8 33.3
Stable disease 11 47.8 8 33.3
Progressive disease 2 8.7 8 33.3
Total patients = 23 Total patients = 24
To discern the impact of treatment on the size and number of tumour lesions, patients are assessed at baseline (before treatment) and throughout the study using CT scans or magnetic resonance imaging. Tumour response outcomes are categorised using the widely accepted RECIST (Response Evaluation Criteria In Solid Tumours) system. Possible outcomes include complete response (disappearance of all tumours), partial response (more than 30% but less than 100% reduction in the sum of the longest diameters of 'target' tumour lesions), stable disease (between a 30% reduction and a 20% increase in the sum of lesion measurements) and progressive disease (greater than 20% increase in the sum of lesion sizes or appearance of new lesions).
Confirmation of a complete or partial response requires corroboration of the initial finding by a second scan at least one month after the scan in which the response was first seen. Confirmation of stable disease occurs if a patient has met the stable disease criteria at least once not less than six weeks after study entry. If a patient has progressive disease, they stop receiving treatment and no further confirmation of their response status is required. For the data tabulated above, 9 patients in the AS1404 group and 12 patients in the chemotherapy-alone group have a confirmed RECIST response outcome based on these criteria. Where outcome is unconfirmed, there remains a possibility that final outcomes will differ.
The response outcome data above are based on investigator assessments of patient outcomes. The final assessment of tumour response outcomes at the end of the study will be based on independent assessment of patient scans from the trial carried out by a reviewer who is 'blinded' with respect to the treatment each patient received. Results of the independent assessment could potentially differ from those based on investigators' reports.
All the data described above are derived from patients who received AS1404 at 1200 mg/m2, the dose chosen for the phase II programme. There is, however, a phase Ib component to the lung cancer trial, in which a small number of patients received other doses of AS1404 in combination with chemotherapy. The single patient who received 600 mg/m2 AS1404 has a confirmed partial response according to the investigator's assessment. Among the first three of six patients receiving 1800 mg/m2, investigator assessments currently show two with unconfirmed partial responses and one with ongoing stable disease.
In addition to the lung cancer study, Antisoma is conducting two other phase II studies of AS1404, in prostate and ovarian cancers.
AS1404 and the Roche alliance
Roche has worldwide development and commercialisation rights to AS1404 under its 2002 alliance agreement with Antisoma. To maintain its interest, Roche will be obliged to make a milestone payment to Antisoma if and when the drug starts phase III trials and then to fund in full the cost of these trials.
General background on AS1404
AS1404 (chemical name DMXAA) is a small-molecule derived from xanthenone acetic acid. A member of the class of drugs known as 'vascular disrupting agents', it is the only representative of its subclass in clinical trials and is the first of these drugs to report efficacy data from a controlled study. AS1404 was discovered by Professors Bruce Baguley and William Denny and their teams at the Auckland Cancer Society Research Centre, University of Auckland, New Zealand. It was in-licensed by Antisoma from Cancer Research Ventures Limited (now Cancer Research Technologies) in August 2001.
Preclinical models show that AS1404 causes necrotic death of the centre of tumours by disrupting their blood supply. AS1404 has completed three 'monotherapy' phase I trials including around 120 patients with various cancers. Published preclinical data show additive or more than additive effects when AS1404 is combined with a range of cancer treatments, with some of the most promising results seen with taxanes such as paclitaxel. All of the phase II studies of AS1404 currently ongoing are evaluating the effects of the drug in combination with taxane-based chemotherapy regimens.
Background on lung cancer
According to Globocan, incidence of lung cancer in North America, Europe and Japan (the major markets for cancer drugs) was around 667,000 in 2002. Some three quarters of lung cancer cases are non-small cell lung cancer. The American Cancer Society estimates that approximately 163,510 people in the US will die of the disease during 2005.
Background on Antisoma
Based in London, UK, Antisoma is a biopharmaceutical company that develops novel products for the treatment of cancer. Antisoma fills its development pipeline by acquiring promising new product candidates from internationally recognised academic or cancer research institutions. Its core activity is the preclinical and clinical development of these drug candidates. In 2002, Antisoma formed a broad strategic alliance with Roche to develop and commercialise products from Antisoma's pipeline. AS1404 is included within the Roche alliance. Please visit www.antisoma.com for further information about Antisoma.
Disclaimer Except for the historical information presented, certain matters discussed in this statement are forward looking statements that are subject to a number of risks and uncertainties that could cause actual results to differ materially from results, performance or achievements expressed or implied by such statements. These risks and uncertainties may be associated with product discovery and development, including statements regarding the company's clinical development programmes, the expected timing of clinical trials and regulatory filings. Such statements are based on management's current expectations, but actual results may differ materially.