Can Rockwell Medical win FDA approval for its dialysis drug?

FDA reviewers have little doubt that Rockwell Medical's ($RMTI) iron-replacement treatment for dialysis patients met its goals in late-stage trials, but the company, seeking agency approval, may have trouble convincing regulators that its Phase III results can translate into real-world benefits.

Rockwell is due before the FDA's independent Oncologic Drugs Advisory Committee on Thursday to defend Triferic, a drug designed to noninvasively deliver iron to the bone marrow of dialysis patients. In documents posted ahead of the meeting, FDA staff noted that Triferic met its primary endpoints of boosting hemoglobin and serum iron in chronic kidney disease sufferers across two Phase III trials, but reviewers also flagged an alarmingly high drop-out rate and questioned whether Rockwell's analysis adequately demonstrates the drug's effect.

Particularly troublesome to regulators: Fewer than 20% of patients made it all the way to either study's 48-week end mark, and about half didn't even get to 20 weeks. That led to "a considerable amount" of missing data, reviewers wrote, casting doubts on "the validity and robustness of the efficacy results."

And "a large portion" of those dropouts discontinued because they needed anemia treatment with erythropoiesis-stimulating agents (ESAs), drugs designed to spur the production of red blood cells. That result confounds Rockwell's secondary goal of securing a label touting Triferic as effective at reducing the need for ESAs.

Furthermore, Rockwell handed in Phase II data designed to demonstrate that lessened need for ESAs among patients taking Triferic compared to those on placebo, but agency staff was unconvinced by the results, pointing out that while the drug contributed to a reduction in prescribed doses of ESA, actual dosing wasn't significantly different.

Thus the FDA's principal question for its advisory panel: "Given the extent of subjects who withdrew from the study early ... and differential reasons for such early withdrawal, does the primary efficacy endpoint analysis adequately capture the benefit of the treatment?"

The committee will take up the issue Thursday, voting on whether to recommend approval for the intravenous drug. The FDA is not required to follow the opinions of its chosen experts, though it generally does, and the agency is scheduled to make a final decision on Triferic's application by Jan. 24.

- read the briefing (PDF)