BioWorld International Correspondent
BRUSSELS, Belgium - The European Medicines Agency has just revealed why it finally turned down in July an application for a new antineoplastic based on anti-sense technology.
Genta Development Ltd., of London, had applied for a marketing authorization for Genasense (oblimersen) in January 2006 as an infusion for treatment of patients with advanced or metastatic melanoma.
No statistically significant difference regarding the primary endpoint of overall survival was demonstrated in the single pivotal trial, and data-driven subgroup analyses on overall survival only can be considered as hypothesis-generating, the agency's scientific committee concluded.
"Taking into consideration that efficacy has not been established and that significant toxicity is associated with Genasense treatment, the benefit/risk balance is negative," the committee recommended the refusal of the granting of a marketing authorization.
In June 2006, after an initial review, the agency sent the company a list of questions. It reviewed the answers in January 2007, and decided additional information was needed. Further contacts with the company over subsequent months failed to meet the concerns of the agency, which issued a negative opinion on the application in April.
Genta demanded a review of the decision, and the agency re-examined the dossier and further information in May and June, but in the light of the overall data submitted, and of further scientific discussion, the agency issued a final negative opinion in July.
Oblimersen sodium, a synthetic phosphorothioate oligonucleotide, is a linear strand of DNA comprising 18 nucleotides, with a sulphur atom replacing one of the non-bridging oxygen atoms in the backbone. The sulphur modification is introduced to make oblimersen more resistant to metabolic clearance in vivo.
The agency published a justification of its decision on Oct. 31, exposing many of the inadequacies it identified in the application, including sample sizes that were "too small to draw reliable conclusions," a study design in which "the demonstration of clinical efficacy was not possible," "a relevant increase of adverse events which is felt to outweigh the uncertain benefits," and "lack of independent review."
European Union ministers have yet again failed to reach a decision on the legitimacy of Austria's continuing ban on import of GM products. (See BioWorld International, Oct. 31, 2007.) Their failure means the decision will be referred to EU officials, who are expected to make a ruling in the coming weeks.