After taking a stock hit on the ominous promise of a conference call the next morning, Rockwell Medical Inc. turned investor worries around with news that the firm had encouraging top-line data to offer from the Phase III study known as CRUISE-1, testing SFP, an iron-delivery drug for chronic kidney disease patients on dialysis.

Shares of the Wixom, Mich.-based firm (NASDAQ:RMTI) sank more than 13 percent in after-hours trading Wednesday but surged upward when the Phase III facts became public, and closed Thursday at $4.35, up 59 cents, or 15.7 percent.

Rockwell said SFP, an iron compound that is delivered to hemodialysis patients via dialysate, replacing the 5 mg to 7 mg of iron that's lost during a dialysis treatment, met its primary endpoint, reaching a statistically significant mean change in hemoglobin from baseline to end of treatment.

SFP achieved key secondary endpoints, too, including maintenance of hemoglobin, maintenance of reticulocyte hemoglobin and increase in serum iron pre-to-post treatment without an increase in ferritin. CRUISE-1 is the first of two identical studies to enable Rockwell's new drug application. CRUISE-1 started in March 2011, whereas CRUISE-2 started in July of that year, with results expected in October.

Specifically, CRUISE-1 yielded a mean hemoglobin change difference between SFP and placebo patients of 3.6 g/L in favor of SFP, a statistically significant rate (p = 0.011).

The compound is not only easy to administer as compared to intravenous (I.V.) iron, but also it "appears to be the only iron able to maintain hemoglobin without increasing ferritin," which is a marker that betrays stored iron and inflammation problems, wrote Andrew McDonald, analyst with LifeSci Advisors, in a research report last month, when CRUISE-1 completed dosing.

SFP is introduced into the sodium bicarbonate concentrate that subsequently is mixed into dialysate (the fluid that moves through the dialyzer). Once there, SFP enters the bloodstream and binds to apo-transferrin for transport to bone marrow, similar to the way dietary iron gets assimilated.

McDonald, working from earlier data from an SFP Phase II trial called PRIME, predicted success with CRUISE-1 , since PRIME helped form the basis for the Phase III program. He also forecast that the FDA would grant priority review for SFP, because using the compound decreases the use of costly erythropoietin-stimulating agents (ESAs), with their boxed warnings about cardiovascular reactions and stroke.

Investors' eyes are mostly on SFP, as if Rockwell's future depends on it. "Some might point to the experience of Affymax [Inc., of Palo Alto, Calif.], which is facing bankruptcy due to the recall of its treatment for anemia in patients with chronic kidney disease, Omontys [peginesatide]," McDonald wrote, but Rockwell has a $50 million operating business, more dialysis drugs and products in its portfolio, including the vitamin D injection Calcitriol, which the company is preparing to launch. (See BioWorld Today, May 13, 2013.)

Vindicated by the data, McDonald issued another report, noting that patients treated with SFP experienced a 0.6 g/L increase in hemoglobin levels while patients in the placebo group experienced a 3 g/L decrease in hemoglobin. "This result clearly demonstrates SFP's ability to maintain patient hemoglobin levels," he wrote.

If there were any sticking point to the SFP data, it was the trial dropout rate: 45 percent in the SFP arm and 54 percent in the placebo arm. "Dialysis units can get very touchy about having patients staying in studies with hemoglobins either dropping or going up above [proscribed] levels, given the safety concerns that have been brought up in the community," said Raymond Pratt, Rockwell's chief medical officer, during a conference call with investors to discuss the results.

Adjusting ESA Fixes Hemoglobin Levels

Comparing CRUISE-1's or PRIME's methodology with the ways other trials have been conducted is futile, Pratt said, because "the other iron studies have all been conducted in patients with iron deficiency anemia, and were very short-term studies. We're working on being a maintenance therapy for replacing iron losses for patients during dialysis, so therefore we did a very long study." An open-label experiment "is still ongoing, so we don't have any data we can share with you at this point," he added.

"Typically, in the real world – and again, going back to the PRIME study, which was very similar to what you would see in the real world – you would see that patients whose hemoglobin would be rising" get less ESA treatment administered; in those with hemoglobin dropping, ESA would be increased. SFP "won't eliminate the need completely for I.V. iron, when people become iron deficient, but the SFP group reduced that usage of I.V. iron by about 50 percent," Pratt said.

ESA doses in the CRUISE-1 trial were "clamped," Pratt noted. "They could not be changed during the course of participation in the trial. So in the real world, as we saw in the PRIME study, ESA doses were changed over time to match the hemoglobin values according to the algorithms that are out there for use of ESAs. So, this was a study that was designed to maintain patients within the safety bands that have been established by the anemia guidelines for hemodialysis patients. And when patients exceeded or dropped out of that, rather than keep them in the study, they were removed to the open-label study, where normal practice could then be retained. So these patients were not 'dropped out.' They were removed prospectively because of the design of the study."

Interrogators on the call seemed largely satisfied with the answers.

Pratt said SFP likely "will be used in dialysis patients to maintain their hemoglobin therapy and replace the iron losses that occur during each dialysis treatment from residual blood left in the dialyzer circuit and the multiple phlebotomies that these patients undergo all the time," and, overall, the compound "should decrease the use of ESAs, and it should also reduce the need for repetitive megadoses of intravenous iron in this patient population."

Full results from CRUISE-1 will be offered at the American Society of Nephrology meeting in November, the company said.

Asked about commercialization plans, CEO Robert Chioini said the company "expect[s] to get this drug out to all the dialysis providers" in a rather fragmented market, of which two major providers – Davita Inc. and Fresenius Medical Care Holdings Inc. – control about two-thirds. "We would expect that, with these groups, we would negotiate with them, they would do some evaluation, and if they decide to go with the drug, they would roll it out to all their clinics," he said.

Rockwell, which had previously focused on dialysate products, rebranded itself in 2008 to target end-stage renal disease and chronic kidney disease drugs, deploying an infrastructure already in place.