Cystadrops

Pharmacotherapeutic group: Ophthalmologicals, other ophthalmologicals; ATC code: S01XA21. Mechanism of action Mercaptamine reduces the accumulation of cystine crystals in the cornea by lowering cystine levels through conversion of cystine to cysteine and the formation of mixed mercaptamine–cysteine disulphides. Clinical efficacy and safety Three clinical studies have been conducted with Cystadrops: a single-arm clinical study in 8 children and adults (study OCT-1); a randomised, multicentre, open-label, active-controlled phase III clinical study (study CHOC) conducted in 32 patients; an open-label, multicentre, single-arm study (CYT-C2-001) conducted in 5 patients under 2 years of age. Study OCT-1 This study evaluated the safety and efficacy of Cystadrops over 5 years. Dose adjustments were made following ocular examination. None of the patients discontinued treatment during the 5-year follow-up. Efficacy was assessed using the in vivo confocal microscopy (IVCM) total score, which quantifies cystine crystals across 7 corneal layers. After 30 days of treatment, with a median frequency of 4 instillations per day, a mean 30% reduction in the IVCM total score was observed. The mean 30% reduction in cystine crystal deposits compared with baseline was maintained throughout the dosing regimen, with a median of 3 drops/eye/day (range 1–3 drops) in 7 of 8 patients. Photophobia tended to improve over time. Study CHOC This was a randomised, controlled study evaluating the efficacy and safety of Cystadrops over a 90-day treatment period at a dosing regimen of 4 drops/eye/day. The IVCM total score was the primary endpoint. Fifteen patients were exposed to Cystadrops. The mean IVCM total score was calculated in 11 patients. On day 30, a trend towards a lower IVCM total score was observed in the Cystadrops arm. On day 90, a mean reduction of 40% was confirmed in the Cystadrops arm. Superiority of Cystadrops over the control arm (mercaptamine hydrochloride 0.10%) was demonstrated, p<0.0001, 95% CI (2.11; 5.58). Superiority of Cystadrops was also demonstrated for investigator-assessed photophobia compared with the control arm (mercaptamine hydrochloride 0.10%), p=0.0048, 95% CI (0.23; 1.14). Paediatric population Clinical safety and efficacy data were collected across 3 clinical studies (OCT-1, CHOC and CYT-C2-001). A total of 20 paediatric patients were exposed to Cystadrops, of whom 5 were under 2 years of age. The youngest patient enrolled was 13 months old. Safety and efficacy outcomes were similar in adult and paediatric populations. Pharmacotherapeutic group: Ophthalmologicals, other ophthalmologicals; ATC code: S01XA21. Mechanism of action Mercaptamine reduces the accumulation of cystine crystals in the cornea by lowering cystine levels through conversion of cystine to cysteine and the formation of mixed mercaptamine–cysteine disulphides. Clinical efficacy and safety Three clinical studies have been conducted with Cystadrops: a single-arm clinical study in 8 children and adults (study OCT-1); a randomised, multicentre, open-label, active-controlled phase III clinical study (study CHOC) conducted in 32 patients; an open-label, multicentre, single-arm study (CYT-C2-001) conducted in 5 patients under 2 years of age. Study OCT-1 This study evaluated the safety and efficacy of Cystadrops over 5 years. Dose adjustments were made following ocular examination. None of the patients discontinued treatment during the 5-year follow-up. Efficacy was assessed using the in vivo confocal microscopy (IVCM) total score, which quantifies cystine crystals across 7 corneal layers. After 30 days of treatment, with a median frequency of 4 instillations per day, a mean 30% reduction in the IVCM total score was observed. The mean 30% reduction in cystine crystal deposits compared with baseline was maintained throughout the dosing regimen, with a median of 3 drops/eye/day (range 1–3 drops) in 7 of 8 patients. Photophobia tended to improve over time. Study CHOC This was a randomised, controlled study evaluating the efficacy and safety of Cystadrops over a 90-day treatment period at a dosing regimen of 4 drops/eye/day. The IVCM total score was the primary endpoint. Fifteen patients were exposed to Cystadrops. The mean IVCM total score was calculated in 11 patients. On day 30, a trend towards a lower IVCM total score was observed in the Cystadrops arm. On day 90, a mean reduction of 40% was confirmed in the Cystadrops arm. Superiority of Cystadrops over the control arm (mercaptamine hydrochloride 0.10%) was demonstrated, p<0.0001, 95% CI (2.11; 5.58). Superiority of Cystadrops was also demonstrated for investigator-assessed photophobia compared with the control arm (mercaptamine hydrochloride 0.10%), p=0.0048, 95% CI (0.23; 1.14). Paediatric population Clinical safety and efficacy data were collected across 3 clinical studies (OCT-1, CHOC and CYT-C2-001). A total of 20 paediatric patients were exposed to Cystadrops, of whom 5 were under 2 years of age. The youngest patient enrolled was 13 months old. Safety and efficacy outcomes were similar in adult and paediatric populations.