Sulodexide Gelcaps : An Oral Heparinoid for the Treatment of Diabetic Nephropathy Gets Ready for Phase 3-4 Trial
Mar 17, 2005 - 8:02:38 AM

Keryx Biopharmaceuticals, Inc. announced today that it has finalized a Special Protocol Assessment (SPA) agreement with the Food and Drug Administration (FDA) for the Phase 3 and Phase 4 clinical trials of KRX-101 (sulodexide gelcaps), the Company's drug candidate for the treatment of diabetic nephropathy.

The clinical plan to support an NDA approval for KRX-101 under Subpart H (accelerated approval), as agreed upon with the FDA under an SPA, consists of:

(i) a single Phase 3 trial in patients with microalbuminuria based on the surrogate marker of regression of microalbuminuria as the primary endpoint;

(ii) supportive data from previously conducted clinical studies; and

(iii) substantial recruitment into our Phase 4 confirmatory study that will measure clinical outcomes in patients with overt nephropathy, or macroalbuminuria.

As part of commitment to the FDA, the company plans to commence the Phase 4 trial at approximately the same time as the start of the Phase 3 trial.

The Special Protocol Assessment (SPA) process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for a new drug application.

Subpart-H guidelines allow for the use of surrogate endpoints in pivotal Phase 3 trials to support NDA approval, with confirmatory studies completed post-approval.

Michael S. Weiss, Chairman and Chief Executive Officer of Keryx, commented, "We would like to thank the FDA for their substantial input and guidance in this process."

Keryx's lead compound under development is KRX-101, a first-in-class, oral heparinoid for the treatment of diabetic nephropathy, a life-threatening kidney disease caused by diabetes. More than 20 studies have been published assessing the safety and efficacy of KRX-101 in diabetic nephropathy and other vascular conditions.

A randomized, double-blind, placebo-controlled, Phase 2 study of the use of sulodexide for treatment of diabetic nephropathy was conducted in 223 patients in Europe, and was published in the June 2002 issue of the Journal of the American Society of Nephrology. The results of this Phase 2 study showed a dose-dependent reduction in proteinuria, or pathological urinary albumin excretion rates.

In the third quarter of 2003, they announced that the Collaborative Study Group (CSG), the world's largest standing renal clinical trial group comprised of academic and tertiary nephrology care centers, would conduct the U.S.-based Phase 2/3 clinical program for KRX-101 for the treatment of diabetic nephropathy.

The CSG has previously conducted multiple large-scale clinical trials resulting in over 40 publications in peer-reviewed journals. In addition, the CSG conducted the pivotal studies for two of the three drugs that are currently approved for treatment of diabetic nephropathy. In the fourth quarter of 2003, Keryx initiated the Phase 2 portion of the Phase 2/3 clinical program for KRX-101, and in the third quarter of 2004, we completed the target enrollment for this Phase 2 portion of the clinical program.

In January 2005, the Company announced that the CSG recommended proceeding to the Phase 3 portion of the Phase 2/3 clinical program of KRX-101, as planned.

This recommendation was based on the completion, by an independent Data Safety Monitoring Committee, or DSMC, on January 4, 2005, of a safety evaluation of the first interim analysis from the approximately 150-patient, randomized, double-blind, placebo-controlled Phase 2 clinical trial of KRX-101, and an efficacy assessment of the same data set conducted by the CSG.

Pursuant to this recommendation, and in accordance with its commitment to the FDA, Keryx expects to commence its pivotal program, including both Phase 3 and Phase 4 studies for KRX-101, in the first half of 2005.

Keryx holds an exclusive license to KRX-101 in the territories of North America, Japan and certain other markets.

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