AS1413 regimen yields high response rate and durable responses in patients with secondary AML, a poor-risk population underserved by current treatment options
London, UK, Cambridge, MA, and New Orleans, LA: 7 December 2009 -Antisoma plc (LSE: ASM; USOTC: ATSMY) announces that positive final data from a phase II trial of AS1413 in patients with secondary acute myeloid leukaemia (secondary AML) were presented this weekend at the American Society of Hematology (ASH) meeting in New Orleans. Follow-up of patients has now been completed, and full results are available:
* Eighty-eight patients with secondary AML received the novel DNA intercalator AS1413 together with cytarabine as first-line (remission-induction) therapy * The remission rate was 42%, with 39% of patients achieving a complete remission and 3% a complete remission with incomplete bone marrow recovery * The median duration of remission was 9.4 months, and 30% of those who achieved remission were still alive 2 years after treatment * Clinical benefit was maintained in older patients, with patients over 60 achieving remission rates and remission durations similar to those of patients under 60 * Median survival for all patients was 6.6 months * The safety profile of the regimen was manageable and acceptable, and consistent with that expected for AML remission-induction therapy
Dr Harry P. Erba, Associate Professor of Internal Medicine at the University of Michigan Health System, Principal Investigator in the trial, and presenter of the data at ASH, said: "The phase II study of AS1413 in secondary AML has produced encouraging data, with a 42% remission rate and a significant fraction of durable responses in this very poor-risk population. Based on these promising findings, a large, randomised phase III trial is evaluating AS1413 in patients with secondary AML."
Secondary AML is a well-characterised subset of AML that evolves from a prior myelodysplastic syndrome or develops following radiotherapy or chemotherapy treatment for other cancers. This contrasts with de novo AML, where there is no obvious history leading to the disease. A diagnosis of secondary AML carries a worse prognosis than de novo AML. Moreover, secondary AML is often associated with other adverse risk factors. Dr Erba added: "Patients with secondary AML have a very poor prognosis. In the AS1413 phase II study, most patients were over 60 and almost half had leukaemic cell karyotypes associated with unfavourable outcome."
One adverse risk factor that is common in secondary AML is multi-drug resistance (MDR). This can occur when leukaemic cells produce molecular pumps that expel chemotherapy drugs. MDR affects many drugs, including the anthracyclines daunorubicin and idarubicin, which are commonly used alongside cytarabine as standard remission-induction treatment for AML. AS1413, by contrast, is unaffected by MDR, since it evades the major MDR mechanisms, including Pgp, MRP-1 and BCRP. AS1413 has been shown to retain activity against MDR-positive leukaemia cells, and this could be a reason for the observed difference in remission rates between the AS1413 phase II trial and previous trials that used anthracyclines in similar patients, where complete remission rates of 24% and 26% were reported.
Treatment regimens based on AS1413 may be preferable to anthracycline-based approaches in various settings where MDR compromises anthracycline activity. The phase II trial reported at ASH and the ongoing phase III trial of AS1413 have focused on patients with secondary AML because this group represents a significant unmet medical need, with a high prevalence of MDR and poor outcome with standard, anthracycline-based regimens.
The phase III ACCEDE trial compares AS1413-based and anthracycline-based regimens as remission-induction therapy for secondary AML. It randomises 450 patients 1:1 to AS1413 plus cytarabine or daunorubicin plus cytarabine. Recruitment is proceeding rapidly, and data from the trial are expected in late 2010 or early 2011.
Bill Lundberg, MD, Project Leader for AS1413 at Antisoma, commented: "We're very pleased with the support from physicians and patients around the world for the ACCEDE study, which tests the idea of replacing the anthracycline daunorubicin with the novel DNA intercalator AS1413 as the partner for cytarabine in remission-induction treatment of secondary AML. We hope that this trial will build on the positive findings from our phase II study and lead to the introduction of AS1413 as a new standard for the treatment of secondary AML."
Glyn Edwards, Antisoma's CEO, added: "AS1413 has distinctive features that could translate into real benefits for patients. We look forward to seeing the phase III data in secondary AML and believe that AS1413 could ultimately have potential in various blood cancer settings."
An additional poster presentation given yesterday by Drs Ben Downie and James Foran of the University of Alabama at Birmingham considered whether certain karyotypes (different anomalies in the cancer cell chromosomes) were predictive of patients' outcomes in the phase II study. A monosomal karyotype, which has recently been found to predict poor outcome in de novo AML patients, was found to have a similar predictive value in the secondary AML patients studied in the AS1413 phase II trial.
Copies of both posters are available on the Antisoma website at http://www.antisoma.com/asm/products/as1413/
Enquiries: Antisoma plc: Glyn Edwards, CEO
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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.
About AML AML is a type of cancer in which the bone marrow makes abnormal and immature blood cells, eventually leading to bone marrow failure. The American Cancer Society estimates that there will be around 13,000 new cases of AML diagnosed this year in the US alone. Antisoma estimates that 3,000-5,000 of these patients will have secondary AML (AML evolving from a myelodysplastic syndrome or following chemotherapy or radiotherapy treatment for other cancers).
About AS1413 AS1413 (amonafide L-malate) was added to Antisoma's pipeline through the acquisition of Xanthus Pharmaceuticals, Inc. in June 2008. AS1413 is a novel DNA intercalator that induces apoptotic signalling by blocking topoisomerase II binding to DNA. This differs from the action of classical topoisomerase II inhibitors, which induce apoptosis by causing extensive DNA damage. A further distinctive feature of AS1413 is its ability to evade Pgp and related transporters responsible for multi-drug resistance (MDR). A pivotal phase III trial is evaluating AS1413 as a treatment for secondary AML, a condition often associated with MDR. This follows a phase II trial in the same population, from which final data are reported here and earlier data have been presented at conferences including the 2008 ASCO and ASH meetings. Antisoma is developing AS1413 independently and plans to commercialise the drug itself in the US while seeking partnerships for commercialisation in other territories.
About Antisoma Antisoma is a London Stock Exchange-listed biopharmaceutical company that develops novel products for the treatment of cancer. The Company has operations in the UK and the US. Please visit www.antisoma.com<http://www.antisoma.com> for further information about Antisoma.
Posted: December 2009