The good news for Rockwell Medical Technologies is that most of the FDA’s advisers believe dialysis supplement Triferic is effective in arresting haemoglobin loss in patients with chronic kidney disease. The bad news is that the agency looks unpersuaded by the group’s argument that Triferic can reduce use of Epogen and other erythropoietin-stimulating agents (ESAs).
Given the pressure on regulators to enable safer substitutes to ESAs, Rockwell’s iron solution still could earn approval for the US markets, especially as many of the alternatives have struggled with hypersensitivity reactions. But without the ESA-sparing claim, the company may find it has limited ability to command a premium price and justify its place in bundled dialysis payments.
Is this the real life?
The 8-3 advisory committee vote in favour of Triferic was not as categorical a win as a unanimous decision, but is being taken as a sign of improved odds that Rockwell could have a drug approved for sale in the US by the PDUFA action date of January 23. Investors certainly took it that way – shares were up 15% to $10.73 in early trading.
Triferic is an iron compound mixed with sodium bicarbonate at kidney dialysis centres and then introduced into dialysate fluid to replace the iron lost during such treatments. It differs from such iron-supplement products as Injectafer, Venofer and Feraheme in that those treatments require a separate infusion – all of those products have warnings about hypersensitivity reactions.
FDA staff raised objections to Rockwell’s statistical analysis both on the change in haemoglobin levels contained in the pivotal Cruise programme against placebo as well as phase II ESA-sparing data. The problem with the Cruise trials was that the trial called for treatment of 48 weeks but just 18% completed the entire protocol. Thus “it is difficult to draw inferences about effects during the complete 48 weeks,” according to FDA staff.
These were withdrawals mandated by the study’s anaemia-management safety protocols, but it constitutes “missing data” that calls into question the robustness of the findings as well as the validity of the entire trial design, the FDA wrote in its briefing document.
As for the ESA claim, the FDA disputed the company’s claim that treatment with Triferic led to a reduction in ESA use. The company reported that Triferic patients in that trial saw their average prescribed ESA dose rise 7.3%, statistically less than the rise of 37.3% seen in a placebo group – however, the FDA reported that the actual ESA use rose 12.5% in the Triferic patients and 42.2% in the placebo group, a non-significant difference.
More work needed?
Showing that reduction in ESA use would make Triferic a much more exciting product, but as it stands it merely looks like it could be a safer offering without compelling efficacy data to back it up. Even the safety claim may not be a winner as there were six cases of suspected hypersensitivity among the 1,400 patients in the Triferic clinical trial programme. This does not necessarily count it out of the approval stakes, however.
History shows that positive FDA votes are by no means a guarantee of approval. The FDA reviewers must now decide whether the eight votes in favour reflect a clinical appetite for what Triferic has to offer or, instead, is a sign that the reviewers could find no reason to object to it. Given that products addressing this condition already exist, it could well be an easy decision for FDA to demand more rigorous data, and perhaps to provide better comparisons against current clinical practice.
In the event of approval, the group will still need to persuade dialysis providers why they should disrupt current clinical practice in order to work Triferic into the mix. Rockwell, a dialysis supply company, has well-established ties with clinic operators, but on the ground the clinicians may be a harder sell.