Keryx Aims For Ironclad Hold On Hyperphosphatemia Market

Recently-approved (and still un-trade named) phosphate binder ferric citrate could unseat the market leader due to its unique ability to increase iron in patients, firm believes, although it didn’t get the full set of labeling claims it sought.

Despite entering a crowded field with a firmly entrenched market leader, Keryx Biopharmaceuticals Inc. believes it can turn its recently approved phosphate binder into the dominant player due to some strong differentiators, even though its product label is not as extensive as the investment community had been hoping.

Keryx’s first commercial product, ferric citrate, a non-calcium based phosphate binder for the control of serum phosphate levels in patients with chronic kidney disease (CKD) on dialysis, cleared FDA Sept. 5. Ferric citrate was previously known as Zerenex, but FDA didn’t approve the name. The company is still in discussions on a brand name and is hoping to have that hammered out before the product launch in early December (Also see "Zerenex To Be Positioned As Cost-Saving, Oral Alternative In ESRD Setting" - Pink Sheet, 12 Mar, 2013.).

Keryx hopes to expand to pre-dialysis CKD patients, and will start a trial soon.

While its label has similar efficacy and safety messages as other phosphate binders – including Sanofi/Genzyme Corp.’s Renvela (sevelamer carbonate), which has 55% of the market – the ferric citrate label has the warning that it may cause iron overload and requires possible reduction and even discontinuation of I.V. iron.

The ferric citrate label also notes that the drug increases serum ferritin and transferrin (TSAT) levels, but does not include any of the data surrounding these endpoints in the clinical trials section of the label – something that displeased investors greatly.

“We had a very robust Phase III program and the investment community was expecting more of that data in the label itself,” Keryx Chief Operating Officer Greg Madison acknowledged in an interview, but stressed “if we didn’t think we had enough differentiators to do the right thing for patients and really go out and market this effectively, we would not have stopped negotiating with FDA.”

The ferric citrate label includes two Phase III clinical trials, including a 56-week study that compared the drug to an active comparator and a four-week fixed-dose study that looked at the serum phosphate levels in patients based on doses of one, six or eight pills per day (Also see "So Far So Good: With Phase III Data, Keryx Says Zerenex Will Stand Out In ESRD Crowd" - Pink Sheet, 1 Dec, 2010.).

In the active controlled trial, ferric citrate was able to lower phosphorus levels and maintain that effect consistent with the active control. After week 52, patients in the ferric citrate arm of the study were re-randomized to either drug or placebo and given another four weeks of treatment. Patients given placebo saw an increase in their serum phosphate levels of 2.2 mg/dL compared to those on ferric citrate (p<0.0001).

The fixed-dose trial showed that doses of six to eight pills per day were much more effective than a single pill daily. Mean reduction in serum phosphorus at four weeks was 0.1 mg/dL with one tablet/day, 1.9 mg/dL with six tablets/day, and 2.1 mg/dL with eight tablets/day.

The trials had four secondary endpoints that showed how ferric citrate controlled the various elements of iron – but the full data regarding those endpoints was not included in the label.

What’s In A Label?

For Keryx, the mention of iron increases in the label still represents a win. End-stage renal disease (ESRD) patients often have trouble with iron absorption, particularly during dialysis, resulting in the need for I.V. iron administration several times per week. Ferric citrate is the only phosphate binder that has been shown in clinical trials to increase iron absorption as well as regulate phosphate levels.

That small mention in the label is what Keryx is banking on to make it the market-leading phosphate binder – a market currently worth about $1.3 billion and growing.

“The single most important differentiator for us has been that we have a phosphate binder that causes increases in serum ferritin and serum TSAT. That is the single biggest differentiator when we think about commercialization strategy and when we think about how we are going to attack this market overall. It allows us to go out there and talk about this product in a very aggressive way,” Madison said.

Despite early ambitions to partner ferric citrate, Keryx has opted to go it alone in the U.S. The concentration of target nephrologists within dialysis centers should make this an easy indication for a small company to market without the deep pockets of a big pharma partner. While the company is well past the point of seeking a partner in the U.S., Keryx is still conducting talks with potential partners in Europe and expects a decision on its filing there in mid-2015.

The company intends to give ferric citrate a “coming out party” at the American Society of Nephrology meeting in Philadelphia in November, said Madison, who indicated the company will have a large presence at the conference. But the drug will hit the market in early December, with 59 sales reps across six regions. The company has been negotiating with payers and expects to have “a baseline of reimbursement” in place by the time of launch with further rolling formulary coverage over the next year.

The drug will likely be priced in-line with the current standard of care, but Keryx has yet to make a definitive decision on pricing just yet. JMP Securities analyst Michael King expects the drug to be priced below market leader Renvela, providing another point of differentiation.

“We note that our ferric citrate pricing assumption of $425 per month is substantially below that of the wholesale acquisition cost (WAC) of competitive drugs like Velphoro ($1,026 per month) and Renvela ($1,114 per month),” he wrote in a Sept. 5 note.

Dialysis Centers Could Save A Bundle

Keryx has already begun engaging the major dialysis centers – even though the oral drug is not included in the bundling system like I.V. dialysis drugs and prescriptions are filled at retail pharmacies by patients. The company expects to have conversations with the 20 payers that cover 80% of dialysis centers before launch.

For dialysis centers, the Keryx drug could hold major appeal. Reducing the use of I.V. iron as well as erythropoietin-stimulating agents (which ferric citrate also did in clinical trials) will bring down the costs associated with the typical dialysis bundle and increase the revenues to the center.

“Clinics will be able to cut the cost of treatment and realize greater revenue from the ‘bundle.’ Additionally, there are several significant peer-reviewed publications that detail the multitude of benefits to patients, including ESA sparing, decreases in infections, and decreased hospitalizations,” King said in his note.

“We feel this is a major differentiator for ferric citrate and will likely increase its market adoption due to physician recognition of the major health benefits to patients and economic benefits to their practice,” added King.

Ferric citrate’s effects on iron aren’t just a competitive distinction in its current market – CKD patients on dialysis – but could allow Keryx to expand beyond that market to CKD patients who have yet to start dialysis. Many of these patients have trouble controlling their iron levels and oral iron supplements carry their own set of nasty side effects that often lead to patient noncompliance.

Keryx believes it could be positioned to have a strong place in this market as well – an indication that no other phosphate binder carries. The company is expected to begin a late-stage trial in this patient population in the coming weeks.

Despite the strong case that Keryx makes for the prospects of its drugs, some of its competitors have been having a harder time cracking into this market. Vifor Pharma Ltd. launched its own hyperphosphatemia drug Velphoro (sucroferric oxyhydroxide) in December. Vifor is claiming that it has the advantage of convenience; Velphoro requires 3.3 pills per day on average to control phosphate levels, while Renvela requires nine and ferric citrate requires eight pills daily (Also see "Will Velphoro’s Convenience Advantage Be Enough In Crowded ESRD Field?" - Pink Sheet, 3 Dec, 2013.).