Threshold Pharmaceuticals, Inc. changes the status of its TH-070 clinical development program for BPH (Benign Prostatic Hyperplasia).

As a result of abnormalities observed in liver enzyme levels in 6 subjects in ongoing clinical trials, the US FDA has placed the US TH-070 program on partial clinical hold and has requested that the company provide additional information related to the drug's acceptable dose and duration of treatment in BPH patients. These abnormalities include 3 serious adverse events observed at 3 months of dosing in the phase 3 European/Canadian clinical trial and 3 additional observations of elevated liver enzymes that occurred in other ongoing clinical trials.

The company is amending the phase 3 European/Canadian trial to discontinue dosing. 567 patients have been enrolled in this study, virtually all whom have completed 28 days of dosing.

"Our main priority right now is the safety of our patients and we are working with the FDA to resolve these safety issues as quickly as possible," said Alan Colowick, Threshold's chief medical officer.

Lonidamine (TH-070) was originally approved for the treatment of cancer in 3 European countries in the mid-1980's. Published randomized clinical trials of Londiamine in approximately 3500 cancer patients did not reveal statistically significant elevations in liver function tests. In the company's previous single centre phase 2 TH-070 trial, one patient had transient elevated liver enzymes.

The company plans to collect and analyze all the data, including the 28- day treatment data from approximately 750 patients who are participating in the phase 2 US trial and the phase 3 trial being conducted in Europe and Canada. Threshold expects these results to be available in the third quarter of 2006.