Ever since ImmunoCellular Therapeutics (NYSEMKT:IMUC) released relatively disappointing results from its Phase 2 study with ICT-107, there has been a lot of speculation as to whether DCVax from Northwest Biotherapeutics (OTCQB:NWBO) will be any better. Little scientific evidence suggests at the moment that either cancer vaccine is any better than the other. DCVax may eventually prove to be better than ICT-107, but no one will know until results from the ongoing Phase 3 study are available. Even if DCVax improves progression free survival (NYSE:PFS), investors should be aware that the FDA may still not approve the cancer vaccine without positive overall survival (OS) results.
Both NWBO and IMUC are developing dendritic cell (DC) vaccines to treat brain cancer (specifically, newly diagnosed glioblastoma multiforme [GBM]) and have reported similarly amazing Phase 1 clinical results. While there are differences, the technologies are probably more alike than not. Investors should not be comparing the Phase 1 clinical results; the number of patients studied in each trial is too small to make any conclusions.
Without any scientific evidence, speculating how one technology might be better than the other is not very constructive. Sure, it makes sense to target as many tumor-associated antigens as possible to treat cancer. However, Provenge improved survival in prostate cancer targeting only a single antigen. Rindopepimut from Celldex (NASDAQ:CLDX) only targets EGFRvIII, and early clinical results in patients with brain cancer are pretty similar to DCVax. How many tumor antigens need to be targeted? Does targeting more actually improve clinical outcomes? Is targeting the most important tumor antigens enough? No one really knows yet.
There are several reasons why clinical results with DCVax might differ from ICT-107, but one can just as easily provide reasons why there will be no difference. For example, DCVax may have better results than ICT-107 since patients in the control group are treated with peripheral blood mononuclear cells (PBMCs) vs. DCs not loaded with antigen peptide, respectively. Theoretically, unloaded DCs can still elicit an immune response and delay progression, and thus, reduce the separation between the ICT-107 and control groups. On the other hand, immune suppression by regulatory T cells and myeloid derived suppressor cells in the tumor microenvironment may be so strong that activating DCs alone may not be enough to eliminate cancer cells. There is little evidence to suggest that either hypothesis above is true or false.
The debate between DCVax and ICT-107 is kind of a distraction, and investors may be forgetting that DCVax might still not receive FDA approval to treat newly diagnosed GBM even if the DC vaccine can show a statistically significant benefit in PFS. Avastin has yet to receive approval despite improving PFS by about 4 months in newly diagnosed GBM patients. Assuming DCVax can statistically improve both PFS and OS, the FDA will likely grant a conditional approval but require an additional Phase 3 trial with OS as a primary endpoint. Recall that the FDA required Dendreon (NASDAQ:DNDN) to conduct a Phase 3 trial with OS as a primary endpoint to before granting approval for Provenge. If the ongoing Phase 3 study with DCVax results in a non-statistically significant OS difference, the FDA will probably require NWBO to complete another Phase 3 trial to demonstrate an OS benefit before granting approval.
Investors should definitely keep an eye on the FDA's upcoming decision regarding Avastin. If Avastin does not receive an approval to treat newly diagnosed GBM, the likelihood that DCVax is approved on PFS alone will be pretty small. It is not very clear how European regulators will decide on Avastin. The EMEA has been more forgiving regarding PFS in the past.