By Amy Brown
If Celldex (NASDAQ:CLDX) was hoping that "promising" interim data from an ongoing phase II study with rindopepimut in glioblastoma would be enough to reassure investors about the cancer vaccine’s potential, it will have been disappointed by yesterday’s share price reaction: the company's stock fell 10%.
In a press release long on detail, but short on conclusive evidence of efficacy, Celldex said only that trends towards a survival benefit had been seen so far. Interestingly, a lack of firm evidence was not troubling investors in ImmunoCellular Therapeutics (NYSEMKT:IMUC) yesterday; shares in the company jumped 36% on the back of data from a very small single arm phase I trial of its immunotherapy, ICT-107, also in glioblastoma. The only real conclusion that can be drawn from these pronouncements is that companies are not afraid of building hype, and hope, around experimental drugs, when at best cautious optimism is called for.
Targeting a Response
To be fair to Celldex, it is still too early to call the phase II React study a failure, and the trends the company laid out yesterday will provide those betting on success with evidence for their case. Still, the interim data should not raise hopes too far. Glioblastoma has proved again and again an incredibly tough cancer to treat.
Celldex is recruiting patients who have tested positive for the EGFRvIII mutated oncogene, which is associated with particularly bad survival prospects and provides the target for the immune-stimulating rindopepimut. The React study comprises two groups, patients either naïve or refractory to Avastin, and only the former group of 70 patients includes a control arm. Results from the first 40 patients who were given rindopepimut and Avastin failed to show significant improvements in overall (p=0.16) or progression free (p=0.47) survival.
This is the first randomised data to emerge for rindopepimut; on a conference call Tom Davis, Celldex’s chief medical officer, described the results as very encouraging, pointing to a stronger trend towards overall survival and suggesting that if the data hold up, it could move into significance. He also highlighted strong immune responses to the drug, with high antibody titers seeming to correlate with longer survival; final data should be available in the second half of next year.
A confirmatory randomised double blind study called ACT IV, already recruiting, will provide the real test of rindopepimut in this setting. Seeking to sign up at least 450 patients and with 350 enrolled so far, data are still some way off.
Hype and Hope
Celldex released its data at the Fourth Quadrennial Meeting of the World Federation of Neuro-Oncology, where the ImmunoCellular data was also presented. This was from a phase I study of ICT-107 that recruited 16 glioblastoma patients between 2007 and 2010; a press release was put out by Cedars-Sinai, which licensed the product to ImmunoCellular and owns a stake in the company.
This chose to highlight that half of the patients in the trial were still alive after five years, adding that typically only 10% of these patients survive more than five years. However it failed to set out how patients were selected for the trial, or highlight the difficulties of drawing any firm conclusions from a single arm, small study.
ICT-107, a six-antigen dendritic cell vaccine, is also being tested more rigorously, in a randomised, double blind phase II study in 200 newly diagnosed patients; results are due any time now. Only if this trial demonstrates a significant improvement in overall survival, will a jump in the company’s share price be justified.
As such, ImmunoCellular’s share price increase yesterday looks misplaced. Celldex’s drop was also probably an overreaction, given the minimal read across possible to the crucial ongoing ACT IV study. The main message is that for the time being rindopepimut and ICT-107 remain far from proven therapies.
Clearly, companies need to keep interested parties informed about the progress of their products. But the line between hype and hope must be walked responsibly, if only for the sake of patients suffering from these diseases, who offer their precious time for these studies.