Ferric Citrate – Auryxia™ – Demonstrates Safety and Cost Savings in Dialysis Patients

Dr. Julia Lewis, MD, Lead Investigator Nephrologist and Professor of Medicine Vanderbilt University Medical CenterMedicalResearch.com Interview with:
Dr. Julia Lewis, MD, Lead Investigator

Nephrologist and Professor of Medicine
Vanderbilt University Medical Center

Medical Research: What is the background for this study? What are the main findings?

Dr. Lewis: The 48-week Open Label Extension (OLE) study for Auryxia™ (ferric citrate) was conducted to determine long term safety following the Phase 3 52-week active-control period. The study also evaluated changes in serum phosphorus, transferrin saturation (TSAT), serum ferritin, hemoglobin, hematocrit and additional parameters, as well as intravenous (IV) iron and erythropoiesis-stimulating agent (ESA) usage.

In the OLE study, Auryxia demonstrated long-term safety in dialysis-dependent chronic kidney disease (CKD) patients. The results were consistent with those seen in the published pivotal Phase 3 trial.

The study demonstrated that the adverse events (AE’s) profile of Auryxia was similar to that seen in the Phase 3 52-week active-control period. AEs occurred in 142 patients treated with Auryxia. They were primarily non-serious gastrointestinal (GI) – related AE’s, including diarrhea, nausea, vomiting and constipation. Serious adverse events occurred in 75 patients, though none were related to Auryxia. In addition, there were no clinically or statistically significant differences in liver enzymes or aluminum levels observed from baseline to the end of the 48 weeks.

Similar to the original trial, we witnessed excellent phosphorus control with the drug, along with an increase and then a plateau in serum ferritin and TSAT levels with Auryxia. The plateauing of serum ferritin and TSAT further supports iron absorption is highly regulated by the gastrointestinal track as seen in the 52-week active control period. This suggests that the body absorbs iron as needed for effective erythropoiesis.

Additionally, iron store increases from ferric citrate resulted in, by the end of the extension study, 85% of subjects not using any IV iron.

We presented this data at the 2014 American Society of Nephrology Meeting. The abstract can be found online at www.asn-online.org.

Medical Research: What should clinicians and patients take away from your report?

Dr. Lewis: The results of the OLE study provide further confirmation of Auryxia’s potential in the dialysis setting. Patients on dialysis take several medications to manage metabolic factors like elevated phosphate levels and iron deficiency that are common in end-stage renal disease. Having an absorbable iron-based phosphate binder with unique pharmaco-dynamic properties may be of clinical value to doctors treating patients in the dialysis setting. Ferric citrate has been demonstrated to effectively bind phosphorous while increasing iron stores, resulting in decreased usage of IV iron and ESA and sustaining hemoglobin.

Also, recent data regarding the pharmaco-economic impact of Auryxia showed patients treated with Auryxia had a savings of $896 per-patient-per-year (PPPY), due to a reduction in infection-related adverse events, $1,021 PPPY due to a reduction in gastrointestinal-related adverse events, and $1,033 PPPY due to a reduction in cardiac-related adverse events, with lower overall rates of hospitalization in all three categories. To arrive at these conclusions, researchers examined the results of the Phase 3 52-week active-control period, and looked at the rate of serious adverse events compared to active control in relation to standard billing practices and adjusted for inflation. Medicare payment rates were applied, and overall costs were measured PPPY.

The data from this study led by my colleague Dr. Roger Rodby was also recently presented at the 2014 American Society of Nephrology Meeting. The abstract can be found online at www.asn-online.org.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Lewis: The population of patients with early CKD and iron deficiency anemia remains underserved. Further research is still needed however to evaluate current treatment strategies for iron deficiency anemia in early CKD, which are clearly not optimal, and how an iron-based phosphate binder can potentially play a role.

A pivotal Phase 3 study of Auryxia for the treatment of iron deficiency anemia in patients with non-dialysis dependent (Stage 3-5) chronic kidney disease was recently initiated. The ability to treat this common CKD related condition could be greatly beneficial to the patient population, and I look forward to those results.

Citation:

Results from the long-term open label extension (“OLE”) study of Ferric Citrate in dialysis dependent chronic kidney disease (“CKD”) patients with elevated serum phosphorus.

Keryx Biopharmaceuticals Announces Ferric Citrate Presentations at the Upcoming American Society of Nephrology Kidney Week 2014 Annual Meeting

Pharmacoeconomic Abstract Selected for Oral Presentation
Results from a Long-Term Safety Extension Study in Chronic Kidney Disease
Selected as a Late-Breaking Poster Presentation

New York, NY – October 23, 2014 — Keryx Biopharmaceuticals, Inc. (Nasdaq:KERX) today announced  that two Ferric Citrate-related abstracts have been accepted for presentation at the upcoming American Society of Nephrology (ASN) Kidney Week 2014 annual meeting in Philadelphia, PA from November 11-16, 2014.  An abstract regarding the pharmacoeconomic impact of Ferric Citrate has been selected for oral presentation and an abstract with results from the long-term open label extension (“OLE”) study of Ferric Citrate in dialysis dependent chronic kidney disease (“CKD”) patients with elevated serum phosphorus has been selected as a late-breaking poster presentation. Some abstracts are now available on the ASN website.

Details of the presentations are as follows:

Friday, November 14 2014      Abstract # FR-OR045

Description: The potential pharmacoeconomic impact of Ferric Citrate.
Session Name: Dialysis Identifying Risk Factors and Improving Noncardiovascular Outcomes Presentation Time: 4:30PM Saturday, November 15th:
Abstract # SA-PO1102
Description: Results from the long-term open label extension (“OLE”) study of Ferric Citrate in dialysis dependent chronic kidney disease (“CKD”) patients with elevated serum phosphorus.
Session Name: Late-Breaking Posters
Presentation Time:  10:00 a.m. – 12:00 noon

“We are thrilled about the presentations of key clinical and pharmacoeconomic data that we believe can further reinforce Ferric Citrate’s value, at the upcoming ASN conference, occurring just a few weeks before our expected launch,” stated Ron Bentsur, Chief Executive Officer of Keryx. “This conference is an outstanding renal venue known for its high academic standards and typically draws over 10,000 treating nephrologists and dialysis professionals from the U.S. and abroad.”

About Ferric Citrate

Ferric Citrate was approved by the U.S. Food and Drug Administration on September 5, 2014 and is indicated in the U.S. for the control of serum phosphorus levels in patients with chronic kidney disease (CKD) on dialysis. Keryx plans to make Ferric Citrate available to U.S. dialysis patients in early December.

In January 2014, ferric citrate was approved for the treatment of patients with all stages of CKD in Japan, where it is being marketed as Riona® by Keryx’s Japanese partner, Japan Tobacco Inc. and Torii Pharmaceutical Co. Ltd.

Keryx has filed a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA), seeking the approval of Ferric Citrate as a treatment of hyperphosphatemia in patients with CKD, including dialysis and non-dialysis dependent patients, and that application is currently under review.

Ferric Citrate is also being developed in the U.S. as a treatment for iron deficiency anemia in patients with Stage 3 to 5 non-dialysis dependent chronic kidney disease (CKD). The pivotal Phase 3 study in this indication commenced in September 2014.

For Full Prescribing Information for Ferric Citrate, please visit http://www.keryx.com/wp-content/uploads/Keryx_FerricCitrate_PI.pdf.

Important Safety Information about Ferric Citrate

Contraindication:  Patients with an accumulation of iron in their body, e.g. hemochromatosis, should not take Ferric Citrate.

Iron Overload:  Iron absorption from Ferric Citrate may lead to increased iron in storage sites.  Iron parameters should be monitored prior to and while on Ferric Citrate. Patients receiving IV iron may require a reduction in dose or discontinuation of IV iron therapy.

Accidental Overdose of Iron:  Keep Ferric Citrate away from children as it contains iron.  Accidental overdose of iron containing products is a leading cause of fatal poisoning in children under 6 years of age. Call a poison control center or your physician in case of an accidental overdose in a child.

Patients with Gastrointestinal Bleeding or Inflammation:  Safety has not been established for these patients.

Adverse Events: The most common adverse events with Ferric Citrate were diarrhea (21%), nausea (11%), constipation (8%), vomiting (7%) and cough (6%)Gastrointestinal adverse reactions were the most common reason for discontinuing Ferric Citrate (14%).

Ferric Citrate contains iron and may cause dark stools, which is considered normal with oral medications containing iron.

Drug Interactions:  Doxycycline should be taken at least 1 hour before Ferric Citrate.

About Keryx Biopharmaceuticals, Inc.

Keryx Biopharmaceuticals, headquartered in New York, is focused on bringing innovative therapies to market for patients with renal disease. The Company’s lead product, Ferric Citrate, is approved in the United States for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis. Keryx plans to commercially launch Ferric Citrate in the U.S. in the fourth quarter of 2014. In January 2014, ferric citrate was approved for the treatment of patients with all stages of CKD in Japan, where it is being marketed as Riona® by Keryx’s Japanese partner, Japan Tobacco Inc. and Torii Pharmaceutical Co. Ltd.  For more information about Keryx, please visit www.keryx.com.

Cautionary Statement

Some of the statements included in this press release, particularly those regarding the commercialization of Ferric Citrate, 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: whether Ferric Citrate will be successfully launched and marketed in the U.S.; whether the FDA will approve a brand name for Ferric Citrate prior to the projected launch date; 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. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at http://www.keryx.com. The information found on our website and the ASN website is not incorporated by reference into this press release and is included for reference purposes only.

KERYX CONTACT:

Amy Sullivan
Vice President – Corporate Development and Public Affairs
Keryx Biopharmaceuticals, Inc.
Tel: 617.466.3447
E-mail: amy.sullivan@keryx.com