Regulatory Decision Summary for Procysbi

The safety and efficacy of Procysbi for the indication of nephropathic cystinosis, a rare disease, was evaluated based on two studies; RP103-03 and RP103-04.

Study RP103-03 was a randomized, 9-week, open-label non-inferiority trial, in 43 patients with nephropathic cystinosis (aged 6 to 26 years) who were tested in a crossover design comparing Procysbi to immediate release (IR) cysteamine (Cystagon). The primary efficacy results showed that both drugs met therapeutic target (1 nmol ½ cystine/mg protein) for mean peak white blood cell (WBC) cystine levels with a mean difference satisfying the non-inferiority criteria.

Study RP103-04, a separate ongoing, open-label, long-term (up to 3.75 years) study conducted in nephropathic cystinosis patients including 40 patients carried over from RP103-03, 13 patients ≤ 6 years of age, and 6 renal transplant patients, provided descriptive data to support the efficacy of Procysbi.

While efficacy was established with respect to decreased WBC cystine levels, no conclusions could be reached regarding disease outcomes (for example, delay in renal impairment, difficulty swallowing, or quality of life).

Procysbi demonstrated an acceptable risk profile. In Study RP103-03, treatment with Procysbi compared with IR cysteamine, resulted in a higher incidence of adverse events (AEs); mostly gastrointestinal (GI)-related. However, imbalances in GI-related AEs were heavily confounded. The most common treatment-related AEs were vomiting (33.9%), nausea (15.3%), abdominal pain (13.6%), breath odor (13.6%), and diarrhea (8.5%). No deaths were reported in either study.

Studies of cysteamine in rat dams demonstrated teratogenicity, fetotoxicity and growth retardation and decreased survival in nursing neonates. No long term carcinogenicity studies were provided in the submission.

Insufficient data was included for children under 2 years of age, adults over 65 years, patients with hepatic impairment, patients with severe or end stage renal disease, and pregnant or breastfeeding women. The Canadian Product Monograph (CPM) addresses these uncertainties.

Risk minimization tools in the Canadian Risk Management Plan (RMP) include a safety checklist for prescribing physicians, a 6-monthly follow-up safety check list and contact with treating physicians on a 6-month basis.

Overall, the evaluation of Procysbi indicated that long-term treatment was reasonably well tolerated, given its expected clinical benefit. No unexpected safety concerns have been identified to date. The benefit-harm-uncertainty profile for Proscysbi in the treatment of nephropathic cystinosis is considered favorable.