Date: 2015-04-20
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at 2015 Annual Meeting of the American Association of Cancer Research
Company: Aveo Oncology (USA - MA)
Product: AV-380
Action
mechanism: monoclonal antibody. AV-380 is a humanized IgG1 inhibitory monoclonal antibody targeting growth differentiating factor-15, or GDF15, a divergent member of the TGF-ß family, for the potential treatment or prevention of cachexia.
Disease: cancer cachexia
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 20, 2015, Aveo Oncology announced the presentation of results from a preclinical study of AV-380, the Company’s potent, humanized inhibitory antibody targeting growth differentiation factor 15 (GDF15), in a cachectic human tumor xenograft model with significantly increased plasma GDF15 levels. The data were presented in a poster titled “Effective treatment of cancer associated cachexia by AV-380, a GDF15 inhibitory antibody” at the 2015 Annual Meeting of the American Association of Cancer Research in Philadelphia from April 18-22. Cachexia affects the majority of advanced cancer patients and is thought to be responsible for approximately 30% of all cancer deaths. Cachexia is a complex metabolic syndrome associated with malnutrition and severe involuntary weight loss due to the loss of muscle and fat tissue, as well as the clinical manifestation of anemia, inflammation and suppression of immune functions. Current evidence suggests that a pro-inflammatory state may be responsible for many of the symptoms associated with cachexia. GDF15 is a pro-inflammatory cytokine whose elevated circulating levels are significantly correlated with cachexia in cachectic cancer patients and several animal models of cancer cachexia. For the study, mice bearing HT-1080 were treated either with AV-380, or a control antibody. The effect on body weight, muscle/fat mass and organ sizes were assessed. Metabolic changes induced by the treatment were measured by a comprehensive laboratory animal monitoring system (CLAMS). Results demonstrated that the inhibition of GDF15 function results in the complete reversion of the phenotypic and metabolic changes associated with cancer-related anorexia-cachexia syndrome, or CACS, completely reverting body weight loss and restoring normal body composition of the tumor bearing mice. AV-380 treatment resulted in a catabolic to anabolic metabolic switch and increased food intake, energy expenditure, resting energy expenditure and physical activity. The data highlight the potential of AV-380 as a therapeutic intervention for the treatment for CACS. * On September 26, 2014, Aveo Oncology announced the presentation of results from four preclinical studies of AV-380, the Company’s potent, humanized inhibitory antibody targeting growth differentiation factor 15 (GDF15), in various in vivo cachexia models and in vitro assays at the 2nd Cancer Cachexia Conference, being held September 26-28, 2014, in Montreal, Canada. In addition to the poster presentations, the AVEO research was selected for presentation in an oral session titled “Targeting GDF15 with the inhibitory antibody AV-380 for the treatment of Cancer Cachexia.” Data from these posters, titled “Induction of Cancer Cachexia by Inflammatory Molecules in Directed Complementation Tumor Models;” “Complete reversal of CASC in animal models by AV-380, a GDF15 inhibitory antibody;” “The combination of GDF15 blockade with an anti-cancer agent reverses cachexia and significantly prolongs survival in xenograft models;” and “Recombinant GDF15 does not trigger canonical SMAD2 pathway activation in vitro,” together with additional data regarding the role of GDF15 and AV-380 in cancer cachexia, are being submitted for publication in a scientific journal. “These studies demonstrate that elevated levels of circulating GDF15 drive the development of cancer cachexia in mice, and that its inhibition, with AV-380, completely reversed body weight loss and restored normal body composition, including fat, muscle and organ size said Jeno Gyuris, Ph.D., chief scientific officer of AVEO.. We have also demonstrated that the combination of AV-380, an anti-cachexia agent, with an anti-cancer treatment, dramatically prolonged survival compared to mice treated with anti-cancer therapy alone. We look forward to building on these discoveries as we progress AV-380 toward clinical study, expected to begin in the second half of 2015.” Initial clinical development is expected to be for the treatment of cancer cachexia. AVEO plans to evaluate opportunities for partnerships to expand the development of AV-380, including in cachexia associated with non-cancer indications, including chronic heart failure, chronic kidney disease and chronic obstructive pulmonary disease to leverage the full potential of this asset.
