AS1413 (amonafide L-malate, formerly Xanafide®)AS1413 is a DNA intercalator that induces apoptotic signalling by blocking TopoII binding to DNA. Unlike classical TopoII inhibitors, a distinctive feature of AS1413 is its ability to evade PgP and related transporters responsible for multi-drug resistance. AS1413 is currently in phase III development in secondary AML. Secondary AML (acute myeloid leukaemia)AML is divided into two major categories, de-novo and secondary. AML is classified as secondary AML if it occurs as a result of a prior haematological disease or treatment with chemotherapy or radiation therapy or a combination of the two causes. In a phase II trial, treatment with AS1413 plus cytarabine resulted in a complete response rate of 38.6%, with an additional 3.4% showing CRi (complete response without recovery of blood cell count). This compares with CR rates of around 25% seen with standard treatment in similar AML patients enrolled in two large American studies. AS1413 is now in a phase III registration trial called ACCEDE. The ACCEDE trial compares AS1413 plus cytarabine with daunorubicin plus cytarabine in 450 patients Latest presentation AS1413 is distinct from daunorubicin and etoposide, poster presentation at AACR, Washington 2010 Pgp impacts on CR rates in AML, poster presentation at ASCO, Chicago 2010 AS1411 AS1411 has shown activity against a wide range of solid and blood cancer cell lines in preclinical experiments and could therefore have potential against a variety of human cancers. Clinical development is focused on acute myeloid leukaemia (AML).
AS1411 is an aptamer. This is a type of drug based on a short piece of DNA or RNA. However, unlike some other drugs based on these chemicals, aptamers work as conventional drugs, binding to a protein target by virtue of a fit with its three-dimensional structure. The term aptamer is derived from the Greek ‘aptos’ (to fit). AS1411 has a structure that allows it to bind specifically to a protein called nucleolin, which is found on the surface of many cancer cells. Once bound, the AS1411 aptamer is taken into the cancer cell, where it causes death by apoptosis (programmed cell death). A previous phase I trial of AS1411 in 30 patients with various advanced cancers reported no serious adverse events related to treatment and promising signs of anti-cancer activity were seen. Latest presentations AS1411 novel combinations and microarray, poster presentation at AACR, Washington 2010 Long-term outcomes of patients responding to AS1411 regimen, poster presentation at ASCO, Chicago 2010 ASA404ATTRACT-1 phase III trial of ASA404 halted following interim analysis 29 March 2010, London, UK, and Cambridge, MA: www.antisoma.com/asm/media/press/pr2010/2010-03-29/ Antisoma plc (LSE: ASM; USOTC: ATSMY) announces that the planned interim analysis of data from the ATTRACT-1 phase III trial of ASA404 in previously untreated non-small cell lung cancer (NSCLC) has shown that continuation of the trial would be futile, as there is little or no prospect of demonstrating a survival benefit with ASA404 in this setting. The ATTRACT-1 trial will therefore be halted.
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