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Keryx Biopharmaceuticals Reports Positive Phase 2 Study Results Of Zerenex (Ferric Citrate) For The Treatment Of Hyperphosphatemia

November 12, 2017

Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX) announced results of the Phase 2 study of Zerenex (ferric citrate) for the treatment of elevated serum phosphorous levels, or hyperphosphatemia, in patients with end-stage renal disease (ESRD) on thrice weekly hemodialysis. The study was a multicenter, open-label clinical trial, which enrolled 55 patients. The primary objective of this study was to assess the tolerability and safety of Zerenex (ferric citrate) with doses ranging from approximately 1 gram per day to 12 grams per day.

The top line efficacy and safety results from this Phase 2 study were submitted to the FDA, and discussed at a recent face to face meeting with the Division of Cardiovascular and Renal Drug Products. The FDA also reviewed the final reports for the 90-day rat and 16-week canine toxicology studies. The FDA indicated that the results of the Phase 2 study and the toxicology studies were adequate to support entry into a Phase 3 program. Keryx is in the process of finalizing the Phase 3 program in consultation with the FDA.

The FDA also reviewed the protocols for the ongoing chronic toxicology studies (6-month rat and 42-week canine), which can be completed after the Phase 3 program has begun.

In the first part of the Phase 2 study, 34 ESRD patients who were taking approximately 6 to 15 tablets/capsules per day of calcium acetate, calcium carbonate, lanthanum carbonate or sevelamer hydrochloride or any combination of these agents were eligible for enrollment and immediately switched to a starting dose of 4.5 grams per day of Zerenex (ferric citrate). In the second part of the study, 21 ESRD patients who were taking > 12 tablets/capsules per day of calcium acetate, calcium carbonate, lanthanum carbonate or sevelamer hydrochloride or any combination of these agents were eligible for enrollment and immediately switched to a starting dose of 6.0 grams per day of Zerenex (ferric citrate). Patients were treated with Zerenex (ferric citrate) for four weeks and were titrated weekly to achieve and maintain normal serum phosphorus levels, between 3.5 to 5.5 mg/dL, the therapeutic goal.

Although designed primarily as a safety study, key efficacy parameters were evaluated, with results as follows:

At baseline:

-- Baseline mean + standard deviation (SD) serum phosphorus was approximately 5.9 + 1.5 mg/dL immediately prior to the switch to Zerenex (ferric citrate);

-- The average daily dose of PhosLo(R) (calcium acetate) was 6.9 grams per day and for Renagel(R) (sevelamer hydrochloride) was 9.9 grams per day, for patients not on combination therapy prior to the switch to Zerenex (ferric citrate).

Following the treatment period (four weeks on Zerenex):

-- At the end of the treatment period (after four weeks on Zerenex) the mean + SD serum phosphorus was approximately 5.4 + 1.3 mg/dL;

-- The average daily dose of Zerenex (ferric citrate) at the end of four weeks of treatment was 6.8 grams per day.

In the subset of patients who had a serum phosphorus above the normal range (> 5.5 mg/dL) immediately prior to the switch to Zerenex (n = 29), the mean (SD) baseline serum phosphorus was 7.0 (1.1) mg/dL, and at the end of treatment with Zerenex the mean (SD) serum phosphorus was 5.6 (1.6) mg/dL.

In the Phase 2 study, there were four serious adverse events which were deemed unrelated to Zerenex. Darkened stool was reported in the study and was associated with the presence of iron in the gastrointestinal tract. With the exception of the reporting of darkened stool as an (asymptomatic) adverse event, the gastrointestinal adverse event profile was similar in incidence to that reported for other currently marketed phosphate binders. There was no increase in serum calcium noted in the study.

Dr. Julia Lewis, Professor of Medicine at Vanderbilt University, the Principal Investigator in the study, commented, "This study, as well as earlier studies, suggest that Zerenex is an effective, tolerated phosphate binder that will potentially make a significant clinical addition to treating the important universally present problem of hyperphosphatemia in patients with end-stage renal disease."

Ron Bentsur, Chief Executive Officer of Keryx, stated, "The promising safety and efficacy profile of Zerenex indicates that there is significant market potential for the drug in the phosphate binder space." Mr. Bentsur continued, "We're excited to have two late stage clinical drug candidates, Zerenex and KRX-0401 (perifosine), both with compelling Phase 2 data."

About Hyperphosphatemia

In the United States, according to data from the U.S. Renal Data System, there are approximately 485,000 patients with end-stage renal disease, or ESRD, and the number of ESRD patients is projected to rise 60% to approximately 785,000 by 2020. The majority of ESRD patients, over 350,000, require dialysis. Phosphate retention and the resulting hyperphosphatemia in patients with ESRD on dialysis are usually associated with secondary hyperparathyroidism (and its related cardiovascular complications), renal osteodystrophy and soft tissue mineralization. ESRD patients usually require treatment with phosphate-binding agents to lower and maintain serum phosphorus at acceptable levels. The need for alternative phosphate-binding agents has long been recognized, especially given the increasing prevalence of ESRD as well as shortcomings with current therapies. Zerenex has the potential to be an effective and safe treatment in lowering and/or maintaining normal serum phosphorus levels in patients with ESRD and hyperphosphatemia.

Sales of phosphate binders to treat hyperphosphatemia in ESRD patients in the U.S. were approximately $600 million in 2007, and has grown in excess of 20% per annum over the last five years.

About Keryx Biopharmaceuticals, Inc.

Keryx Biopharmaceuticals is focused on the acquisition, development and commercialization of medically important, novel pharmaceutical products for the treatment of life-threatening diseases, including renal disease and cancer. Keryx is developing Zerenex(TM) (ferric citrate), an oral, iron-based compound that has the capacity to bind to phosphate and form non-absorbable complexes. Zerenex has recently completed a Phase 2 clinical program as a treatment for hyperphosphatemia (elevated phosphate levels) in patients with end-stage renal disease. The Company is also developing KRX-0401 (perifosine), a novel, potentially first-in-class, oral anti-cancer agent that modulates Akt, a protein in the body associated with tumor survival and growth. KRX-0401 also modulates a number of other key signal transduction pathways, including the JNK and MAPK pathways, which are pathways associated with programmed cell death, cell growth, cell differentiation and cell survival. KRX-0401 is currently in Phase 2 clinical development for multiple tumor types. The Company also actively engages in business development activities that include seeking strategic relationships for its product candidates and for the Company, as well as evaluating compounds and companies for in-licensing or acquisition. Keryx is headquartered in New York City.

Cautionary Statement

Some of the statements included in this press release, particularly those anticipating future clinical and business prospects for Zerenex and KRX-0401, may be forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Among the factors that could cause our actual results to differ materially are the following: our ability to successfully complete clinical trials for Zerenex and KRX-0401; our ability to meet anticipated development timelines for Zerenex and KRX-0401 due to recruitment, clinical trial results, manufacturing capabilities or other factors; and other risk factors identified from time to time in our reports filed with the Securities and Exchange Commission. Any forward-looking statements set forth in this press release speak only as of the date of this press release.

Source: Keryx Biopharmaceuticals, Inc