Keryx Biopharmaceuticals Inc fka KERX

[califax]

Keryx Rises as Phase III Zerenex Study Readies to Leave the Gate

By Donna Young
Washington Editor
Published May 7, 2010
http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=54457

Investors Thursday drove shares of Keryx Biopharmaceuticals Inc. up 6.8 percent after the firm said it started a short-term Phase III study evaluating Zerenex (ferric citrate), an iron-based phosphate binder, as a treatment for hyperphosphatemia in dialysis patients with end-stage renal disease (ESRD).

Shares of the New York-based biotech (NASDAQ:KERX) closed at $5.95, a gain of 38 cents.

The initiation of the short-term trial marks the commencement of Zerenex's registration program, which also consists of a 58-week long-term safety and efficacy study scheduled to start in the third quarter.

The program is being conducted under a special protocol assessment (SPA) agreed on with the FDA, noted Keryx CEO Ron Bentsur. (See BioWorld Today, Jan. 06, 2010).

For the short-term multicenter, randomized, open-label Phase III trial of Zerenex, Keryx plans to enroll about 150 hemodialysis patients, who must undergo a two-week washout period. The patients will then be randomized to receive a daily fixed dose of Zerenex at 1 g, 6 g or 8 g for 28 days.

The primary endpoint of the study is to demonstrate a dose response in the change of serum phosphorous from baseline to the end of the treatment period, or day 28.

For its long-term multicenter, randomized, open-label, safety and efficacy Phase III trial of Zerenex, Keryx plans to enroll about 300 hemodialysis or peritoneal dialysis patients. That study will consist of a two-week washout period followed by a 52-week safety assessment, in which patients will be randomized at a 2:1 ratio to receive Zerenex or another phosphate binder.

The safety assessment will be followed by a four-week efficacy assessment. Only patients taking Zerenex during the safety assessment will be randomized to continue treatment on the drug or given a placebo during those four weeks.

Keryx plans to file a new drug application for Zerenex as a therapy for hyperphosphatemia in the first half of 2012, Bentsur told BioWorld Today.

He said he was "confident" that Zerenex - for which Keryx licensed the worldwide rights, excluding the Asian Pacific Region, from Panion & BF Biotech Inc. - would capture "meaningful market share" in the global phosphate binder space, which he noted is approaching $1.5 billion in sales.

Bentsur insisted that the drug has shown clear factors that differentiate it from currently marketed medicines to treat hyperphosphatemia in ESRD patients on dialysis, which include Genzyme Corp.'s Renagel (sevelamer hydrochloride) and Renvela (sevelamer carbonate), Shire plc's Fosrenol (lanthanum carbonate) and Fresenius Medical Care North America's PhosLo (calcium acetate).

Fosrenol and PhosLo, Bentsur noted, have "overriding safety concerns."

In PhosLo's case, prescribers must be careful not to give too much of the drug because of the risk of hypercalcemia, or too much calcium in the blood. Fosrenol also carries risks of lanthanum accumulation, Bentsur said, adding that Zerenex does not come with those types of safety issues.

"So at a minimum, we think we could come in and be another alternative and take some additional market share away from those two," he said.

The "bigger prize," however, would be for Zerenex to cut into Renagel's and Renvela's market share, "which are by far the market leaders," Bentsur said, noting that his firm is targeting the "pill burden" of those two agents.

Patients on average must take up to 10 tablets per day of Renagel and Renvela, he noted, calling that a "pretty heavy" pill burden.

"It is a big issue that leads to noncompliance and inconvenience, which patients complain about all of the time," Bentsur said. "We think we can cut that quite substantially, perhaps by even as much as 40 to 50 percent," he argued, noting that Zerenex's tablet is the same size as Renagel and Renvela.

Renagel and Renvela, which are polymer-based products, also have gastrointestinal bloating associated with the drugs.

"We feel that we could have lower rates," Bentsur contended, insisting that Zerenex could provide a better safety, convenience and compliance profile than the two Genzyme drugs.

In addition, Bentsur said, as an iron-based drug, Zerenex also has shown other potential advantages over the currently marketed products.

He noted that ESRD patients on dialysis "without exception" will become iron-depleted to the point they will need intravenous iron or an erythropoiesis-stimulating agent (ESA).

In Keryx's long-term Phase II study of Zerenex, which Bentsur acknowledged was a "small" trial conducted outside of the U.S., the data showed that over time, patients on the treatment had "mild increases" in iron storage parameters, "which is what you want to see in these patients because they are iron-depleted."

Indeed, about 40 percent of the patients in the Phase II study were able to take I.V. iron and ESA holidays, he said.

"It ends up being a benefit to the patients because they are iron-depleted anyway, and they need iron," he said. "If we see that in the Phase III program, that could be a very big advantage for us. The pharmacoeconomic impact of something like that could be pretty tremendous," Bentsur added.

He insisted that the market was ripe for additional phosphate binders, such as Zerenex, "and we think this drug is very well-positioned to capture significant market share."

Now if Keryx can "just execute and meet our timelines and move forward," Zerenex has the potential to do just that, he said.

Keryx also recently started Phase III testing of its other lead compound perifosine in metastatic colorectal cancer and in multiple myeloma.

Those studies also are being conducted under SPA agreements with the FDA, Bentsur said.

"We are in a good position having two drugs pursuing three different Phase III programs all under SPAs," he said, adding that the company has sufficient capital to complete all three trials.

"I think that is a very compelling and unique position for a small biotech company to be in," Bentsur said. "We feel confident about the prospects of the company."