The FDA has granted a priority review designation to a new drug application (NDA) for an oral targeted release formulation (TRF) of budesonide (TRF-budesonide; Nefecon) for the treatment of patients with IgA nephropathy (Berger's disease), according to Calliditas Therapeutics AB, the developer of the treatment.1
The NDA is based on data from the pivotal phase 3 NefIgArd study (NCT03643965), which achieved its primary end point of a significant proteinuria reduction versus placebo at 9 months, and met the key secondary end point of stabilization of the estimated glomerular filtration rate (eGFR) at 9 months. The application is also supported by data from the phase 2 NEFIGAN trial,2 which met the same end points as the NefIgArd trial.
Under the Prescription Drug User Fee Act, the FDA action date for a decision on the NDA is September 15, 2021.
"We are very excited about being granted priority review, which reflects the unmet medical need of IgA nephropathy. We look forward to engaging with the agency and work towards an accelerated approval later this year so that we will be in a position to provide the first approved medication for IgA nephropathy patients," Renée Aguiar-Lucander, CEO of Calliditas, stated in a press release.
The double-blind, multicenter, international phase 3 NefIgArd study randomized adult patients with IgA nephropathy to TRF-budesonide or placebo. Part A of the trial included 200 patients enrolled at approximately 146 locations in 19 countries.
Regarding the primary end point, the mean proteinuria reduction from baseline was 31% in the TRF-budesonide (16 mg) arm versus 5% in the placebo arm (P = .0005). With the key secondary end point of eGFR, TRF-budesonide led to a “a treatment benefit of 7% versus placebo at 9 months, reflecting stabilization in the treatment arm and a 7% decline of eGFR in the placebo arm (P = .0029).”1
The investigators considered the treatment to be well tolerated overall. No new safety signals emerged with TRF-budesonide as compared with the previously documented safety profile of standard budesonide.
The ongoing part B of the NefIgArd study is intended to be a confirmatory post-market observational trial to confirm the long-term efficacy of TRF-budesonide using eGFR as a metric over a 2-year follow-up period from the start of treatment. The second part of the trial accrued an additional 160 patients. Data are expected to read out in early 2023.
IgA nephropathy results from a buildup of the antibody immunoglobulin A in the kidneys.3 The buildup causes local inflammation that can eventually impair the proper function of the kidneys regarding the filtration of waste from the blood.
1. FDA grants priority review for Nefecon, for patients with IgA nephropathy. Published online April 28, 2021. Accessed April 28, 2021. https://prn.to/3t3pE8u.
2. Fellström BC, Barratt JB, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial.Lancet. 2017;389(10084):2117-2127. doi: 10.1016/S0140-6736(17)30550-0
3. IgA nephropathy (Berger's disease). Mayo Clinic. Accessed April 28, 2021. https://mayocl.in/3gMmaVC.