Date: 2014-11-20
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the 26th European Organization for Research and Treatment of Cancer(EORTC) – the National Cancer Institute (NCI) – and the American Association for Cancer Research (AACR) symposium
Company: Isis Pharmaceuticals (USA - CA) AstraZeneca (UK)
Product: AZD5312 (ISIS-ARRx)
Action
mechanism: ISIS-ARRx is a generation 2.5 antisense drug designed to inhibit the production of androgen receptor (AR) for the treatment of patients with prostate cancer. Prostate cancer growth, proliferation and progression are all androgen-dependent, and AR function is involved in disease progression at all stages of prostate cancer. For patients diagnosed with metastatic prostate cancer, current treatments largely involve opposing the action of androgens by blocking the androgen receptor or removing circulating androgens. Although androgen deprivation therapy approaches are initially effective in delaying disease progression in patients with metastatic prostate cancer, over time the course of the disease will progress in many of these patients. Resistance to current therapies is frequent and can occur through a variety of mechanisms including the activation of AR signaling in tumor cells through the amplification, overexpression and mutation of the AR gene. Because ISIS-ARRx can inhibit the production of all known forms of AR, including variants of the AR gene, this drug has the potential to be an effective treatment for all stages of prostate cancer, including prostate cancer patients who are resistant to current therapies.
Disease: prostate cancer
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On November 20, 2014, Isis Pharmaceuticals announced that data from two drugs in its anti-cancer franchise will be presented by researchers at AstraZeneca in three presentations at the 26th European Organization for Research and Treatment of Cancer(EORTC) – the National Cancer Institute (NCI) – and the American Association for Cancer Research (AACR) symposium. Preclinical data from ISIS-ARRx, will be presented in a poster titled, \'Preclinical pharmacology of ISIS 560131, a generation 2.5 antisense oligonucleotide targeting the androgen receptor with differentiated activity from enzalutamide\'. Preclinical data from this presentation shows that ISIS-ARRx can substantially reduce levels of all forms of the androgen receptor, including splice variants that have been implicated in promoting androgen resistance in prostate cancer. Moreover, evidence was presented demonstrating that ISIS-ARRx is effective in prostate cancer models that display resistance to current standard of care prostate cancer treatments. Isis Pharmaceuticals and AstraZeneca entered into a collaboration, development and license agreement in 2012 in oncology, subsequently expanded in 2013 to include CVMD. Under the 2012 agreement, one of the molecules being developed is ISIS-STAT3Rx, a first-in-human, first-in-class, generation 2.5 antisense oligonucleotide inhibitor of STAT3, which is being developed as an immunomodulatory agent in combination with MEDI4736, AstraZeneca\'sinvestigational anti-PD-L1 immune checkpoint inhibitor. A second product of that collaboration, a generation 2.5 antisense drug targeting the androgen receptor, ISIS-ARRx, is in a Phase 1/2 study. This month, Isis and AstraZenecaexpanded their relationship by entering into a collaboration to develop novel delivery methods for antisense oligonucleotides. This new collaboration builds on the existing relationship and could also bring benefits to these programs.
