Abstract: SA-PO560
RP-103 Controls WBC Cystine Levels and Promotes Growth in Treatment-Naive Patients ≤6 Years with Nephropathic Cystinosis
Session Information
- Noncystic Mendelian Diseases
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Genetic Diseases of the Kidney
- 802 Non-Cystic Mendelian Diseases
Authors
- Langman, Craig B., Feinberg School of Medicine, Northwestern Univ., Chicago, Illinois, United States
- Ferreira, Juliana Caires, Instituto da Criança do HCFMUSP, São Paulo, Brazil
- Young, Kyleen, Lurie Children''s Hospital Chicago, Chicago, Illinois, United States
- Vaisbich, Maria Helena, Nephrology, Sao Paulo University Medical School, Sao Paulo, Brazil
Background
Nephropathic Cystinosis (NC) is a recessive disease in which the lysosomal cystine exporter is deficient, intralysomal cystine accumulates, and the biomarker, WBC ½ cystine/mg protein is > 1 nmol. Cysteamine bitartrate (Cys-Bi), is used to lower levels to <1 nmol. Previous trials of RP-103 have converted patients from an every 6h form of Cys-bi to this every 12h formulation.
Methods
We conducted a long-term, prospective, controlled, open-label study of RP-103 in 17 Cys-Bi naive patients with NC in the US & Brazil. The RP103 starting dose was gradually escalated (10%, every 2 weeks) until the WBC ½ cystine level was <1 nmol. We evaluated height and weight at each visit, and safety (incidence of TEAEs and SAEs). Data reported (mean±SD) below will be for 15/17 subjects < 6y of age.
Results
Age was 2.2±0.9y, range 1.04–4.53y. Ten were ♂. Prior to RP-103, the WBC cystine concentration was 3.1± 2.9 nmol ½ cystine/mg protein. At each subsequent time, the mean concentration was < than at Day 1: 2.2±3,Week(wk) 2; 1.1 ±1.3 wk 12; 0.73±0.64, Month(m) 18. By end of study, 76.9% of subjects had a WBC cystine <1nmol. On Day 1, standing height was in the 2.59 ± 4.00 %ile of the reference population, and increased to 3.27±5.69 at wk 2, 6.95±10.88 at wk 12, and 55.36±43.88 %ile at m18. Z-scores for height were –3.16±1.55 at Day 1 and increased to 0.11±1.96 at study end. On Day 1, weight was in the 3.46 ±11.13 %ile and increased at study exit to 32.85±35.58 %ile. All 17 subjects in the Safety Population had at least 1 TEAE, and 8 had at least 1 TEAE considered related to the study drug. Twelve had an SAE, 5 (29.4%) had a TEAE ≥ Grade 3, and 1 (5.9%) died (unrelated to study drug). No TEAEs led to permanent discontinuation of study drug.
Conclusion
RP-103 safely and effectively lowered the biomarker to target (<1 nmol) in young Cys-Bi naive patients with NC. Linear Growth and body mass increased into the normal range for age (z-score) for those ≤ 6y. Thus, Cys-Bi naive patients ≤ 6y with nephropathic cystinosis may safely and efficiently be started on cystine-reduction therapy with RP-103 (Procysbi).
Funding
- Commercial Support – Horizon Pharmaceuticals; Raptor Pharmaceuticals