Failures and Disappointments
But as 2013 closed, it remains clear that success in cancer vaccine development remains few and far between. Although analysts who follow the field made optimistic predictions based on data available in September 2013, some key potential players have not made the cut.
Based on data available at the time, predictions were that three immunotherapy products could reach the market in the 2014–2015 timeframe including Biovest International’s BiovaxID, an autologous idiotype lymphoma cancer vaccine (Id-KLH/GM-CSF), projected to be approved in Canada and the EU in 2013–2014 and in the U.S. in 2017. Other potentially successful candidates in late-stage clinical development included, among others, GlaxoSmithKline’s MAGE A3 in NSCLC and potentially melanoma, New Link’s HyperAcute in pancreatic cancer, Vical’s Allovectin-7 in melanoma, and Bavarian Nordic’s Prostvac in prostate cancer.
In 2012, the FDA denied marketing approval for BioVaxID, requiring that the vaccine undergo another Phase III trial. But this January, Biovest announced that the European Medicines Agency (EMA) accepted its marketing authorization application for BiovaxID (submitted to EMA under the name Dasiprotimut-T Biovest), thus beginning the review process intended to secure approval to market BiovaxID in the EU and to allow prescription and sale of BiovaxID for the treatment of non-Hodgkin’s follicular lymphoma in patients who have achieved a first complete remission.
And Vical announced last August that its Allovectin (velimogene aliplasmid) failed to meet key endpoints in a Phase III trial in patients with stage III/IV metastatic melanoma and that it will not develop the vaccine further. The vaccine failed to demonstrate a statistically significant improvement in objective response rate at greater than or equal to 24 weeks, its primary endpoint, or in overall survival, the secondary endpoint, when compared with first-line chemotherapy, the company said.
Allovectin is a plasmid-based immunotherapeutic that expresses the HLA-B7 and β2 microglobulin genes, forming a major histocompatibility class I complex. Investigators had hoped that the vaccine, through multiple mechanisms of action, could provoke immune responses that target treated and distal lesions.
Last September, GlaxoSmithKline (GSK) reported that its targeted cancer immunotherapy MAGE-A3, incorporating recombinant MAGE-A3 protein and a novel immunostimulant, AS15 (a combination of QS-21 Stimulon adjuvant, monophosphoryl lipid A, and CpG7909, a TLR-9 agonist), failed its first co-primary endpoint in a Phase III study for melanoma, failing to produce better results than a placebo in enhancing disease-free survival. The company says it will carry on with the study to determine whether the second primary endpoint—testing the immunotherapy in a genetically defined subpopulation—will provide better efficacy, with data expected in 2015.
“We remain committed to identifying a patient subpopulation who may benefit from this investigational treatment," said Vincent Brichard, head of immunotherapeutics at GSK Vaccines.