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Zerenex Phase III Data Wow; Keryx Hits 52-Week High

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By Marie Powers
Staff Writer

Three weeks ago, Keryx Biopharmaceuticals Inc. CEO Ron Bentsur faced tough questions at the 31st Annual J.P. Morgan Healthcare Conference in San Francisco about continuing delays in reporting long-term Phase III data on Zerenex (ferric citrate) for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD) on dialysis.

On Monday, those doubts were laid to rest when the company reported the compound met its primary and all key secondary endpoints in the study, sending shares (NASDAQ:KERX) to a 52-week high of $6.86.

Responding to skeptical analysts at J.P. Morgan, Bentsur acknowledged the company was equally frustrated with delays in reporting results, which were initially expected by mid-December. He blamed the holdup on a one-week shutdown of the company's East Coast-based contract research organization due to Hurricane Sandy, followed by year-end holiday schedules and the departure of a site coordinator. (See BioWorld Today, Jan. 11, 2013.)

Zerenex seemed worth the wait. Investors and analysts were blown away by the Phase III findings, which showed a significant change in serum phosphorus compared to placebo over the study's four-week efficacy assessment period. In addition, Zerenex increased ferritin and transferrin saturation (TSAT) and reduced the use of intravenous (I.V.) iron and erythropoiesis-stimulating agents (ESA) compared to active control over the study's 52-week safety assessment period – findings that could potentially offer greater long-term value for the drug.

The randomized, multicenter, open-label safety and efficacy trial enrolled 441 ESRD patients on hemodialysis or peritoneal dialysis randomized 2:1 during a 52-week safety assessment to Zerenex or active control (Renvela [sevelamer carbonate, Sanofi SA] and/or Phoslo [calcium acetate, Fresenius Medical Care]). During a subsequent four-week efficacy assessment, patients who received Zerenex during the safety assessment were again randomized 1:1 to continued treatment with Zerenex or to placebo. Subjects were titrated during the study to achieve serum phosphorus levels that ranged between 3.5 to 5.5 mg/dL.

Oral iron therapy was not permitted during the study, and I.V. iron therapy was permitted only if a subject's serum ferritin level fell below 1,000 ng/mL or the TSAT fell below 30 percent. Use of ESAs was at the discretion of physicians.

Zerenex met the primary efficacy endpoint with an increase from 5.3 mg/dL in mean serum phosphorus at baseline to 7.2 mg/dL at week 56 compared to a decline in the placebo group from 5.2 mg/dL at baseline to 4.9 mg/dL at week 56 (p < 0.0001).

During the safety assessment period, Zerenex maintained serum phosphorus in the normal range, with favorable and consistent measurements in mean serum phosphorus concentration at weeks 12, 24, 36, 48 and 52, compared to baseline.

Keryx Looking Ahead to Anemia

On a conference call early Monday morning, Bentsur was quick to cite secondary efficacy endpoints related to iron, which he described as "statistically significant" in comparison to Renvela or Phoslo.

The pre-specified iron-related endpoints were selected to corroborate prior data suggesting Zerenex may increase iron storage parameters and reduce the need for I.V. iron and/or ESAs.

Zerenex demonstrated 25.8 percent treatment improvement from baseline to week 52 in mean TSAT compared to a -3.2 percent change for the active control group, and a 51.6 percent decrease in median I.V. iron intake compared to the active control group.

The compound also demonstrated a statistically significant treatment difference compared to active control in mean hemoglobin change from baseline to week 52.

"We said all along that Zerenex was the only phosphate binder that had the potential to transcend into another dialysis category – in this case, anemia management – and generate some benefit," Bentsur said.

The company said complete safety and efficacy data from the study will be presented at a future medical conference.

Despite lingering concerns about the ability of Zerenex to compete commercially with soon-to-be generic phosphate binders, Roth Capital Partners LLC analyst Joseph Pantginis described the long-term Phase III results as dazzling, reiterating Keryx's "buy" rating and raising the price target from $7 to $15.

"Zerenex now has a meaningful opportunity to become the first phosphate binder to also have clinical meaningful properties to manage anemia associated with dialysis patients," Pantginis wrote in a research note, predicting commercialization in 2014.

Similarly, Brean Capital LLC analyst Jonathan Aschoff pointed to reductions in cumulative I.V. iron and ESA use for patients on Zerenex "not only alleviating infection risks and allergic reactions associated with I.V. iron, but also saving costs." In his model, Aschoff tripled Keryx's target price, from $5 to $15.

On Monday, shares of New York-based Keryx gained $2.63, or 76.6 percent, to close at $6.06.

More than 67 million shares changed hands, far eclipsing the stock's previous one-day peak volume when the company axed Sulonex (sulodexide oral gelcap) in diabetic nephropathy in 2008. Keryx's pipeline was trimmed to a single compound last year, after oral Akt inhibitor perifosine failed to improve overall survival in a Phase III trial in colorectal cancer. (See BioWorld Today, March 11, 2008, and April 3, 2012.)

With the completion of the Zerenex registration program, conducted under an FDA special protocol assessment, Keryx plans to submit a new drug application (NDA) to the FDA and a marketing authorization application to the European Medicines Agency in the second quarter, according to Bentsur.

Zerenex also is in Phase II development in the U.S. to manage phosphorus and iron deficiency in anemic patients with Stage III to V nondialysis-dependent chronic kidney disease.

Excluding certain Asian Pacific countries, Keryx holds a global license to Zerenex. Last month, Japanese partner Japan Tobacco Inc. and Torii Pharmaceutical Co. Ltd. filed an NDA for ferric citrate in Japan for the treatment of hyperphosphatemia in patients with chronic kidney disease.