Stuart Sprague1, DO, FASN; Suresh Vayalakkada2, PhD; Guru Reddy3, PhD; Shalabh Gupta3, MD; Pramod Gupta3, PhD
1NorthShore University Health System; 2Formerly Unicycive Therapeutics, Inc; 3Unicycive Therapeutics, Inc
Background
- Elevated phosphate concentrations are associated with a significantly increased risk of cardiovascular events and mortality in patients with chronic kidney disease1
- Current KDIGO guidelines recommend lowering elevated serum phosphorus concentrations toward the normal range in patients with end-stage kidney disease on dialysis through restriction of dietary phosphorus intake, increase in clearance by dialysis, and the use of phosphate binders2
- However, 78% of patients are not adherent to phosphate binders3, possibly due to the phosphate binders’ large size and high pill burden4
- This high daily medication volume creates a barrier to adherence and can negatively impact the quality of life
- Thus, a phosphate binder that maintains efficacy with a lower daily medication volume could improve adherence, quality of life, and potentially clinical outcomes
OBJECTIVE
The goal of this study was to assess the volume of oxylanthanum carbonate required to bind 1 g phosphate and to compare it with other currently available phosphate binders, to determine which binder allows for the highest normalized potency with the lowest daily medication volume
Methods
- Six phosphate binders were assessed: ferric citrate (210 mg ferric iron), calcium acetate (169 mg calcium), lanthanum carbonate (500 and 1,000 mg lanthanum), sevelamer carbonate (800 mg sevelamer carbonate), sucroferric oxyhydroxide (500 mg ferric iron), and oxylanthanum carbonate (500 and 1,000 mg lanthanum)
- Table volume measurements were taken using fluid displacement in corn oil or water
- Mean daily dose volume was calculated as volume per tablet multiplied by the mean number of tablets taken per day
- Volume to bind 1 g of phosphate was calculated by dividing the volume per tablet by its in vivo binding capacity, based on NIH DailyMed website5
Results
- The daily dose volume of oxylanthanum carbonate was 2.3 cm3/day, and the range of volumes for all other phosphate binders was 5.5-9.7 cm3/day (Figure 1)
- Binding to 1 g of phosphate required 5.6 cm3 of oxylanthanum carbonate (7.5 pills) compared with lanthanum carbonate (19.8 cm3, 7.4 pills), calcium acetate binders (25.0 cm3, 33.3 pills), ferric citrate (46.5 cm3, 50.5 pills), and sevelamer carbonate (73.4 cm3, 68 pills) (Figure 2)
CONCLUSIONS
- Oxylanthanum carbonate and sevelamer carbonate had the lowest and highest daily dose volume, respectively
- The daily dose volume of oxylanthanum carbonate was 3- to 4-fold lower than other phosphate binders
- Oxylanthanum carbonate has the lowest volume to bind the same amount of phosphate compared to other binders
DISCUSSION
- With a low medication volume and high phosphate binding capacity, oxylanthanum carbonate, a novel investigational nanotechnology product, can be a welcoming choice for patients to manage their hyperphosphatemia
- The drug’s decreased size (making it easy to swallow) and tolerability have the potential to increase medication adherence and phosphate control
References:
1.Lopes MB, et al., Nephrol Dial Transplant.2020.
2.KDIGO. Kidney Int Suppl (2011). 2017.
3.Van Camp YP, et al. J Nephrol. 2014.
4.Arenas MD, et al. Nefrología. 2010.
5.https://dailymed.nlm.nih.gov/. Accessed 15 September, 2022.
Acknowledgments:
Writing support was provided by Xelay Acumen Group, Inc., and funded by Unicycive Therapeutics, Inc.