(THLD - Get Report)
presented new data Saturday showing how pancreatic cancer patients who "crossed over" in a mid-stage clinical trial of TH-302 may have hampered the drug's ability to demonstrate a stronger improvement on overall survival.
When these crossover patients were excluded from the analysis of the phase II study, the survival benefit attributable to TH-302 improved.
The new analysis was an effort by Threshold to alleviate investor concerns about the future of TH-302. The company's stock price has fallen by 20% over the past two weeks because of worries that TH-302 would not help patients live longer in a larger, phase III trial scheduled to start soon.
Threshold shares closed Friday at $7.24
The phase II study enrolled 214 pancreatic cancer patients and randomized them to treatment with TH-302/gemcitabine or gemcitabine alone. As presented earlier this year, treatment with
TH-302/gemcitabine led to a two-month improvement in progression-free survival
of 5.6 months compared to 3.6 months for gemcitabine alone. The benefit in PFS was statistically significant, although there were some imbalances in patients' baseline criteria that favored TH-302 and may have skewed results.
An analysis of
overall survival from the TH-302 study
was less favorable. TH-302/gemcitabine reduced the relative risk of death by 4.5% compared to gemcitabine alone -- a small survival benefit that was not statistically significant. This survival analysis was made public two weeks and was responsible for the selloff in Threshold shares.
Threshold attributed the modest survival benefit, in part, to patients in the gemcitabine control arm of the study that "crossed over" and began treatment with TH-302 after their tumors began growing again. This made it more difficult for the study to measure the true survival benefit of TH-302 since patients in both arms of the study were treated with the drug.
To add weight to its argument, Threshold on Saturday presented new data from the study that excluded the 38% of patients in the control arm who crossed over to treatment with TH-302. The new data were presented in conjunction with the presentation of the TH-302 phase II data at the European Society for Medical Oncology [ESMO] annual meeting.
Without crossover patients, TH-302 plus gemcitabine reduced the relative risk of death by 24-25% over gemcitabine alone. That's an improvement over the 4.5% risk reduction for death when the crossover patients were factored into the analysis. [Two doses of TH-302 were studied.]