Javelin Pharmaceuticals announced that its US product candidate Dyloject (diclofenac sodium for injection) met primary efficacy endpoints with robust statistical significance in the second of two large pivotal US phase-3 efficacy studies in post-surgical patients with moderate-to-severe pain.

This successful phase-3 pivotal trial in 277 orthopaedic surgical patients randomized subjects to receive one of three treatments every six hours: Dyloject 37.5 mg, ketorolac 30 mg, or placebo. The primary efficacy measure was the area under the curve of pain intensity across time, plotted as the difference from pre-treatment pain compared to placebo. This area was examined stepwise across intervals of 0-24, 0-48, 0-72, 0-96, and 0-120 hours. Dyloject 37.5 mg had statistically significant differences compared to placebo for its primary endpoint across all five time intervals (P< 0.0001 for each of the five intervals). Dyloject's efficacy was numerically although not statistically superior to ketorolac, which in turn was superior to placebo (P<0.0001).

"I am very pleased by the important data. We are well on track to submit a high quality New Drug Application for Dyloject to the US FDA in the second half of 2009. Our open label safety study of Dyloject is rapidly enrolling and will supplement the current US patient safety data base for the submission," stated Martin J Driscoll, Javelin's CEO.

Javelin's chief medical officer, Dr Daniel Carr, stated, "It is gratifying to reconfirm Dyloject's robust effects in this trial in moderate-to-severe pain in postoperative orthopaedic surgical patients, a substantial target population. The fact that doses of Dyloject lower than those previously felt necessary provided statistically significant pain relief in this trial is noteworthy. Further, Javelin has recently presented phase-1 results demonstrating that Dyloject has minimal effects upon platelet function at the same dose tested in this study."

As in earlier trials, this latest Dyloject trial revealed no unexpected safety signals. Adverse events in the present study were similar for Dyloject and placebo. This finding is consistent with the absence to date of any untoward safety signal in the tens of thousands of patients who have received Dyloject in the UK since it was approved there a year ago. Complete analysis of data from this trial will be submitted for presentation at a medical meeting in 2009.

Javelin's first pivotal phase-3 study of Dyloject evaluated patients with acute postoperative pain after abdominal or pelvic surgery, and successfully met its primary and secondary endpoints with statistical significance. Top-line results from that trial were reported in December 2007 and secondary data was presented in August 2008 at the World Congress of the International Association for the Study of Pain.

Dyloject is an injectable formulation of diclofenac in Phase 3 clinical development in the United States and marketed in the United Kingdom.

With corporate headquarters in Cambridge, MA, Javelin applies innovative proprietary technologies to develop new drugs and improved formulations of existing drugs to target unmet and underserved medical needs in the pain management market.