Savient Pharmaceuticals Inc. continued handing out good news about its anti-gout drug Puricase (pegloticase), reporting that the compound met its primary endpoints in two Phase III trials for use in treatment-failure gout patients.
The news keeps Savient ahead in the race to be the first approved therapeutic option for treatment-failure gout sufferers, and the company said it plans to a file biologics license application with the FDA in 2008. Wall Street took notice of the news, sending shares of Savient (NASDAQ:SVNT) up $2.63, or 18 percent, to close at $17.09.
In the two double-blind, placebo-controlled six-month trials (GOUT1 and GOUT2), conducted under a special protocol assessment with the FDA, Puricase 8mg was administered by a two-hour intravenous infusion either every two weeks or every four weeks. The primary efficacy endpoint was normalization of plasma uric acid during months three and six of the trials.
Topline data showed that the mean responder rate for the every two week dose group pooled across both studies was 42 percent (p less than 0.001) and the mean responder rate for the every four week dose group was 35 percent (p less than 0.001), the company reported. In the per protocol analysis the responder rates were higher: every two week was 61 percent (p less than 0.001), and every four week was 50 percent (p less than 0.001), it said. The placebo responder rate was zero in both trials.
Zeb Horowitz, Savient senior vice president and chief medical officer, noted during a conference call that the data are impressive because of the "conservative" trial design that placed all patients who dropped out of the study - regardless of reason - as nonresponders.
Savient also reported that the every two week dose group also attained statistical significance for the a priori definition of reduction of gout tophi - accumulation of nodular masses of uric acid crystals - in the pre-specified pooled analysis. In the every four week dose group data revealed a "favorable numerical trend for this secondary endpoint" but it did not reach statistical significance.
"This is the first time, in a controlled rigorous trials, anyone has been able to show an effect of a drug on gout tophi," Horowitz said.
The occurrence of highly painful and crippling gout flares increased in both dose arms in the early months of the studies, the data showed, but Savient said that is typical for uric acid lowering therapies. In the last three months of the study period both dose arms showed less gout flare frequency compared to the first three months, but failed to meet statistical significance compared to placebo. But the company said that unlike other uric acid lowering therapies, the increase in gout flares induced by pegloticase appears to persist only during the early portion of the treatment period.
While the current studies were targeted at treatment-failed patients, the secondary endpoint results were encouraging enough that the company is considering trials in 2009 for the gout tophi and gout flare indications, said Christopher Clement, president and CEO.
The early analysis indicates that the safety issue "appears to be favorable," Horowitz said, although some patients may not be able to tolerate the drug because of infusion reactions. He said the safety risk "is manageable in the clinical practice setting" because the East Brunswick, N.J.-based company expects the infusion to be handled by specialists and trained infusion nurses.
Competition for pegloticase comes from an oral compound being developed by TAP Pharmaceutical Products Inc. It's febuxostat, a non-purine xanthine oxidase inhibitor, is in Phase III development attempting to settle safety concerns raised by the FDA from a previous new drug application.
Regeneron Pharmaceuticals Inc. in September reported a 10-patient safety study with rilonacept showed a statistically significant reduction in pain scores, and Altus Pharmaceuticals Inc. has ALTU-242 at the preclinical stage. BioCryst Pharmaceuticals Inc. also has a preclinical program in gout.