It's a sad fact in oncology clinical trials that use overall survival as an endpoint -- people have to die for the trials to progress. For developmental-stage drug companies, the wait can be excruciating.
Alfacell (NASDAQ:ACEL) is in that position now with its lead drug candidate, Onconase, which is in its final phase 3 trial for treatment of patients with unresectable malignant mesothelioma. Two hundred and ninety evaluable events -- in this case, patient deaths -- have occurred, but the protocol for the trial requires the company to wait until 316 deaths have taken place before the statistical analysis can be done.
The trial's conclusion has been delayed from the company's previously guided completion date of mid-2007. It's tempting to guess that the low number of deaths thus far is due to the drug extending lives, but unfortunately other possibilities exist. The company might have taken longer than expected to enroll the patients in the trial, or the control group receiving placebos could be surviving longer than expected.
Interim trial data released last year showed that Onconase plus Pfizer's (NYSE:PFE) doxorubicin extended survival of subjects by two months over those treated with doxorubicin alone. If that trend continues through the end of this trial, Alfacell shouldn't have many problems securing an FDA approval, given that the drug is extending the lives of patients by 20%.
Clinical trials taking longer than expected due to a lack of evaluable events is not uncommon. Earlier this summer, GPC Biotech (NASDAQ:GPCB) and Spectrum Pharmaceuticals (NASDAQ:SPPI) pulled their marketing applications after an FDA advisory panel said the drugmakers had to wait until a specified number of deaths had occurred.
Of course, on the rare occasion that a drug works extraordinarily well, an independent data-monitoring committee will stop the trial early because the smaller number of patients is enough to prove the drug is statistically different than placebo. That has occurred not once but twice in liver cancer trials of Onyx Pharmaceuticals' (NASDAQ:ONXX) and Bayer's (NYSE:BAY) Nexavar.
The problem with the extra time Alfacell has to wait is that the trial is almost out of money. The company had $6.5 million in cash at the end of April and a current quarterly burn rate of close to $2 million. It doesn't take a degree in mathematics to figure out that it'll need additional financing soon. Fortunately, Onconase has received fast-track status from the FDA, so much of the New Drug Application (NDA) has already been submitted and reviewed.
Now it needs some positive trial results to complete the NDA and perhaps get a hand up from one of its pharmaceutical big brothers.
