dm+d

Unassigned

New Medicines

TrifericAnaemia in chronic kidney disease; prevention and treatment in patients who are undergoing haemodialysis

Information

Triferic
New molecular entity
Not Known
Rockwell Medical

Development and Regulatory status

None
None
Launched
Nov 20In its Q3 2020 presentation, the company indicates that European licensing discussions with potential partners are ongoing [18].

Mar 19: in its 2018 annual report, the company states that it will focus on the IV form for the European market due to its better fit with dialysis techniques used in Europe, Japan and China. Discussions with the EMA have produced guidance on clinical studies needed to file for the IV form in Europe, however the company does not intend to start these studies until a development partner has been found or further capital raised [17].


May 19: product launched in US. Company also developing an IV formulation and hopes to submit NDA to FDA later in 2019 [16].


Mar 19: product still not launched in US due to ongoing discussion over reimbursement; strategy outside US remains licensing / partnering [15].


Jan 18: Rockwell intends to license out Triferic for development in markets outside the US; as of Jan 2018, there is no indication of a European licensee [14].


Jan 15: US FDA has approved Triferic iron replacement for use by adult patients with hemodialysis dependent chronic kidney disease in order to maintain their haemoglobin [11].


Nov 14: FDA Oncologic Drugs Advisory Committee vote 8-3 that Triferic has benefits that outweigh its risks, recommending full approval [9].


May 14: The US NDA will be subject to a standard review and will have a Prescription Drug User Fee Act (PDUFA) action date of January 24, 2015. The PDUFA action date is the goal date for the FDA to complete its review of the NDA. [7]


Mar 14: New Drug Application submitted to the US FDA seeking approval for Triferic (soluble ferric pyrophosphate citrate) for treating iron deficiency in patients with CKD receiving haemodialysis [6].


Sep 13: Rockwell plans to file an NDA with the FDA in the next 4-6 months [5].


Dec 12: Currently in on-going phase III trials [1]

Category

Iron stimulants
12 December 2014Prevalence estimates of anaemia in patients with stages 3-5 CKD is 0.22% in England, however this does not include patients on dialysis [10].
Anaemia in chronic kidney disease; prevention and treatment in patients who are undergoing haemodialysis
Intravenous

Trial or other data

Jul 15: Rockwell Medical announced publication of Triferic PIII CRUISE studies (CRUISE 1 and 2). Both studies successfully met the primary endpoint (mean change in haemoglobin) with a treatment difference of 0.4 g/dL in favour of Triferic (P=0.011 for individual studies, 95% CI; 0.1 to 0.6 g/dL). During the randomised treatment phase, haemoglobin concentrations remained stable in the Triferic treated group while declined in the placebo group. The safety profile of Triferic was similar to placebo treated pts, with both groups experiencing similar proportions of adverse events. The most frequent adverse event was procedural hypotension which was present in 21.6% of Triferic pts and 19.2% of placebo treated pts. No serious adverse events or deaths were attributed to Triferic [12,13].


Nov 14: FDA Panel posted briefing of its assessment of Triferic based on the CRUISE studies. Notes suggest concerns around clinical usefulness of data given that half of the dialysis patients discontinued the study before 12 months.[8]


Sep 13: Rockwell announces their second PIII CRUISE-2 trial meets its primary and secondary outcomes [5].


Jul 13: Top-line results from the long-term PIII CRUISE-1 reported. The study met its pre-defined primary efficacy endpoint, which was change in Hb from baseline to end-of-treatment between the SFP and placebo groups. The mean difference was 3.6 g/L (95% CI 0.8, 6.3) in favor of SFP (p=0.011). The two groups had similar Hb levels at baseline (109.6 g/L and 109.0 g/L): mean adjusted change 0.6 g/L (95% CI -1.7, 2.8) in the SFP group and -3.0 g/L (95% CI -5.3, -0.8) in the placebo group. There were no differences in frequency or severity between the SFP and placebo groups with respect to AEs or serious adverse events.There were no events of anaphylaxis or hypersensitivity reported with dialysis administrations of SFP [4].


Feb 13: Rockwell Medical reports positive results from the PIII PRIME study. Regular administration of soluble ferric pyrophosphate (SFP)-iron via dialysate reduced use of erythropoietin stimulating agents (ESAs) during hemodialysis by 37.1% while maintaining iron balance & maximizing iron delivery [3].


Dec 12: Rockwell completed enrolment of 300 patients in each of the pivotal CRUISE 1 and CRUISE 2 trials in July 2012, (NCT01320202 and NCT01322347, respectively). CRUISE 1 is underway in the US and Puerto Rico, while CRUISE 2 is underway in the US and Canada. Both trials are investigating the efficacy and tolerability of its continuous iron therapy delivered via dialysate, in chronic kidney disease patients on haemodialysis. These double-blind trials randomised patients 1:1 to treatment with 11 µg/dL ferric pyrophosphate via dialysate or placebo for up to 12 months. The primary endpoint is the mean change in haemoglobin from baseline. Trial designs were finalised with guidance from the FDA. In March 2012, the independent Data Safety Monitoring Board found no safety concerns and recommended that the study continues without modification. A separate interim analysis of data showed that the sample size was appropriate. Completion of these trials is expected in mid-2013, with regulatory submissions planned in the fourth quarter of 2013 [2].