To everyone’s disappointment GenVec needed to pull out its Phase III trial of TNFerade in patients with locally advanced pancreatic cancer. The interim analysis showed 8% lower risk of death, and although mortality reduction in pancreatic cancer should be considered potentially important, with the planned patient number the trial would probably not have reached the required level of statistical significance.
What can we learn?
First, it really was a disappointment for the industry and cancer gene therapy. TNFerade had advantages – at least in theory – over drugs like Advexin with its TNF-Alpha -mediated radio- and chemosensitizing “bystander effect”: TNFerade affects also nearby cells, not just cells directly infected by the vector. I am sure we all would have liked the product to survive Phase III.
Since the announcement, many potential reasons have been raised in public debate. Some people ask if pancreatic cancer, ‘the drug killer’ indication, was a too ambitious target? For sure TNFerade’s story is not at its end yet as it is thought to have a broader applicability.
However, there might be a more fundamental reason for failing to reduce mortality dramatically enough for consideration for approval.
TNFerade is “an adenovector, or DNA carrier, which contains the gene for tumor necrosis factor-alpha (TNFα), an immune system protein, for direct injection into tumors”. So, it is a gene transfer vector – like many others that have not made it to the market for a single reason: maybe the non replication –capable, non-infectivity enhanced gene vectors are just not effective enough, fundamentally?
The next wave of the industry is currently developing replication -capable oncolytic viruses – such as OncoVEX, JX-594, CGTG-102, REOLYSIN and Cavatak – that have high potency in replication and strong local amplification to treat cancer systemically. These results from randomized trials are yet to be published, but the promise of these next wave therapeutics is very strong.