Disease | Compound | Therapeutic class | Endpoints in pivotal studies | Primary neurological endpoints | Biomarker endpoints | Regulatory precedent | Pivotal trial design | Ref. |
---|---|---|---|---|---|---|---|---|
MPS I | Laronidase | Enzyme | Forced vital capacity (% of predicted), 6 min walk distance | No | No | No | RCT, 26 weeks, N = 45, mean age 15.5 years (range 6 – 43 years) | [24] |
MPS II | Idursulfase | Enzyme | Forced vital capacity (% of predicted), 6 min walk distance | No | No | Yes | RCT, 53 weeks, N = 96, mean age 14.2 years (range 5–31 years) | [25] |
MPS VI | Galsulfase | Enzyme | 12 min walk distance, 3 min stair climb test (stairs/min) | No | No | Yes | RCT, 24 weeks, N = 39, (age range 5–29 years) | [26] |
Gaucher disease type I | Alglucerase | Enzyme | Liver and spleen volume change, Hematologic deficiencies, improved mineralization of bone, cachexia and wasting | No | Yes | No | OLT, 36 – 52 weeks, N = 13, mean age 20.3 years (range 7–42 years) | [27] |
Gaucher disease | Imiglucerase | Enzyme | Anemia and thrombocytopenia, liver and spleen volume change, decreased cachexia | No | Yes | Yes | RCT, 26 weeks, N = 30, mean age 32.7 years (range 12 – 69 years) | [28] |
Gaucher disease | Taliglucerase alfa | Enzyme | Hemoglobin concentration, platelet count, liver and spleen volume change | No | Yes | Yes | RCT, 36 weeks, N = 32, mean age 36.2 years (range 19 – 74 years) | [29] |
Gaucher disease | Velaglucerase alfa | Enzyme | Hemoglobin concentration, platelet count, liver and spleen volume change | No | Yes | Yes | RCT, N = 25, 52 weeks, median age 25 years, (range 4–62 years) | [30] |
Gaucher disease | Miglustat | Substrate reduction | Liver and spleen volume change, hemoglobin concentration, platelet count | No | Yes | Yes | OLT, 52 weeks, N = 28, mean age 44 years (range 22–69 years) | [31] |
Fabry disease | Agalsidase beta | Enzyme | Reduction of GL-3 inclusions in capillary endothelium of kidney, heart and skin | No | Yes | No | RCT, 20 weeks, N = 58, mean age 30.2 years (range 16–61 years) | [32] |
Pompe disease | Alglucosidase alfa | Enzyme (bioreactor size: 160 L) | Number of patients who died or needed invasive ventilator support | No | No | No | OLT, 52–106 weeks, N = 18, age range 1 month to 3.5 years | [33] |
Pompe disease | Alglucosidase alfa | Enzyme (bioreactor size: 4000 L) | Forced vital capacity (% of predicted), 6 min walking distance | No | No | No | RCT, 78 weeks, N = 90, mean age 44.4 years (range 10–70 years) | [34] |
Cystinosis | Cysteamine bitartrate IR | Small molecule | Serum creatinine, calculated creatinine clearance, growth (height) | No | Yes | No | OLT, N = 94, mean age 3.8 years | [35] |
Cystinosis | Cysteamine ophtalmic solution | Small molecule | Corneal Cystine Crystal Score | No | Yes | No | OLT, N = 283 (three studies) | [36] |
Cystinosis | Cysteamine bitartrate DR | Small molecule | White blood cell cystine | No | Yes | Yes | RCT, N = 43, mean age 12 years (range 6 – 26 years) | [37] |