May 20, 2009 (Datamonitor via COMTEX) -- GNTA | Quote | Chart | News | PowerRating -- The independent Data Monitoring Board for AGENDA, a Phase III trial of Genta's Genasense in advanced melanoma, has announced that the study can continue to completion. Should Genasense enter the melanoma market - an indication which has been tainted with late-stage drug failures - Genta may finally reap the commercial benefits of its long-term investment in this troubled drug. The independent Data Monitoring Board informed Genta that its Phase III melanoma trial investigating Genasense passed its final futility analysis of progression-free survival (PFS). An independent committee often conducts analyses for 'futility' to ensure that a clinical trial at least has the potential to achieve its main endpoints. Having achieved this recommendation, Genta is able to continue the Phase III trial in order to support a future approval of Genasense in melanoma. The AGENDA trial is a randomized double-blind study involving 315 patients with advanced melanoma. The study aims to determine whether the combination of dacarbazine and Genasense is superior to dacarbazine and placebo in chemotherapy-naive patients. Primary endpoint measures are PFS and overall survival in the two treatment arms. Subsequent futility analyses for overall survival are planned if the PFS endpoint is achieved. Genasense is an antisense oligonucleotide designed to bind to the first six codons of Bcl-2 messenger ribonucleic acid (mRNA). This triggers mRNA degradation and subsequent inhibition of Bcl-2 expression. The Bcl-2 gene is over-expressed in around 80% of tumors and contributes to the development of resistance to chemotherapy, radiotherapy and immunotherapy by inhibition of apoptosis. Genasense has had a troubled development history to date in several indications including chronic lymphocytic leukemia. The drug has been in Phase III development for melanoma since May 2001 and, on many occasions since, has failed to gain regulatory approval for use in this indication. In February 2004, the FDA accepted Genta's New Drug Application for Genasense for first-line melanoma. However, Genta withdrew the application the same year following a lack of efficacy ruling by the Oncology Division Advisory Committee. Genta also withdrew its EU application in July 2007 following a negative opinion from the Committee for Medicinal Products for Human Use. Given the drug's history of negative clinical trial data and safety concerns, Genasense has significant hurdles to overcome. Unless a long and statistically significant survival benefit is shown in the ongoing Phase III AGENDA study, it is unlikely that Genasense's negative physician perceptions will be offset. However, the recent failure of two Phase III melanoma drugs - GSK/Synta's elesclomol in February 2009 and Bayer/Onyx's Nexavar (sorafenib) in April 2009 - reduces potential competitive pressure on Genasense from other pipeline drugs in this notorious indication. |
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