Keryx Biopharmaceuticals announced that the Independent Data Safety Monitoring Committee (DSMC) responsible for monitoring Sulonex (sulodexide oral gelcaps), the company's lead drug candidate under development as a treatment for diabetic nephropathy, recently met to evaluate the data from the ongoing phase 3 trial.
Following a complete review of all available safety and efficacy data, the DSMC found no cogent reason to recommend alteration or termination of the Phase 3 trial. The DSMC raised no safety concerns regarding Sulonex or the trial. As planned, no review was conducted of the safety and efficacy data from the phase 4 trial during this meeting.
Prior to this most recent meeting, the DSMC had previously convened in November 2006, in March 2007 and in August 2007 to review data from the Phase 3 and Phase 4 studies. At each of these meetings the DSMC raised no safety concerns.
On June 18, 2007, the company announced the completion of patient randomizations into the Phase 3 portion of the clinical registration program. The company anticipates that the last patient will complete the active treatment period in mid-December 2007 and the two month off-treatment period in mid-February 2008.
Sulonex is in a pivotal phase 3 and phase 4 clinical programme under a Special Protocol Assessment with the Food & Drug Administration. These trials are being conducted by the Collaborative Study Group, the world's largest standing renal clinical trials group.
The clinical plan to support an NDA approval for Sulonex 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.
The phase 3 clinical program is a multi-centre, randomized, double-blind, placebo-controlled study, comparing 200 mg daily of Sulonex(TM) versus placebo, with a 1:1 randomization between the two arms. The objective of this study is to determine the safety and efficacy of sulodexide in the treatment of patients with type 2 diabetes and persistent microalbuminuria, or diabetic nephropathy, despite being treated with a maximum approved or tolerated dose of an angiotensin II receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEi). The study is designed for patients to be on treatment for six months, followed by two months of evaluation off-treatment.
During the treatment and off-treatment evaluation period, all patients in the study population are expected to continue to receive maximum approved or tolerated doses of ACEis or ARBs. Patients who were not already on maximum approved or tolerated doses of ACEis or ARBs for 120 days were required to go into a run-in period prior to randomization of up to 120 days. This run-in period was designed to stabilize blood pressure and to confirm persistent microalbuminuria while the patients are treated with maximum approved or tolerated doses of ACEis or ARBs.
The primary endpoint for the Phase 3 clinical trial is "therapeutic success" at 6 months, where therapeutic success is defined as (i) conversion from microalbuminuria to normoalbuminuria, as measured by albumin/creatinine ratio (ACR), with at least a 25% reduction in ACR relative to baseline ACR, or (ii) a 50% reduction in ACR relative to baseline ACR.
Concurrently with the phase 3 clinical trial, the company is continuing enrolment into its phase 4 clinical trial, which is a randomized, double- blind, placebo-controlled study, also comparing 200 mg daily of Sulonex versus placebo, with a 1:1 randomization between the two arms. The objective of this Phase 4 study is to determine the efficacy of Sulonex in reducing the rate of progression to End-stage renal disease and adverse clinical sequelae in patients with type 2 diabetes and macroalbuminuria or overt diabetic nephropathy, despite being treated with a maximum approved or tolerated dose of an ARB. All patients in the phase 4 study population are expected to continue to receive maximum approved or tolerated doses of ARBs during the course of the study. The Phase 4 study is designed to enroll approximately 2,200 patients.
The Company has committed to the FDA, as a condition to the approval of Sulonex based on the Phase 3 clinical trial under the guidelines of accelerated approval, that the Phase 4 study would be substantially enrolled at the time of the filing of the NDA for Sulonex.
Sulonex (sulodexide oral gelcap) belongs to a proposed new class of nephroprotective, or kidney protecting, drugs, known as the glycosaminoglycans. A variety of members of this chemical family have been shown to decrease pathological albumin excretion in diabetic nephropathy in humans. Some of the members of this chemical family include the following approved drugs: standard heparin, low molecular weight heparin and danaparoid. These agents all require therapy by injection and are all potent anticoagulants, which are blood thinners capable of inducing bleeding. Sulonex, on the other hand, is given orally and, in this form, has demonstrated little, if any, anticoagulant effects to date.
Keryx owns the exclusive rights to use Sulonex for the treatment of diabetic nephropathy in North America, Japan and certain other markets outside of Europe. Diabetic nephropathy is a long-term complication of diabetes in which the kidneys are progressively damaged. Sulonex is a glycosaminoglycan compound with structural similarities to the broad family of marketed heparins and low molecular weight heparins. This drug has been marketed in a number of European, Asian and South American countries for many years by our licensor for certain cardiovascular conditions and has an established safety profile at the doses used for such indications. Additionally, it has been demonstrated in multiple clinical trials conducted in Europe and the U.S., including two randomized, double-blind, placebo-controlled Phase II studies, that Sulonex can reduce urinary protein excretion in patients with diabetic nephropathy.
Sulonex is in a pivotal Phase 3 and Phase 4 clinical program under a Special Protocol Assessment, or SPA, with the Food & Drug Administration, or FDA. These trials are being conducted by the Collaborative Study Group, or the CSG, the world's largest standing renal clinical trials group.
Keryx Biopharmaceuticals, Inc. is focused on the acquisition, development and commercialization of medically important, novel pharmaceutical products for the treatment of life-threatening diseases, including diabetes and cancer.