Elevidys
delandistrogene moxeparvovec
Species
MonkeyMouse
Longest study
24 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Mouse only (wild-type C57BL/6J and mdx disease model); NHP only in non-GLP supporting studies
“The following toxicology studies were conducted to evaluate the safety of ELEVIDYS following administration in WT and mdx mice.”
Why that species
Disease-model rodents (mdx mice, Dmdmdx rats) used to show micro-dystrophin expression and efficacy; no explicit species-relevance argument
“The pharmacology studies of ELEVIDYS were conducted in rodent models of DMD including mdx mice and Dmdmdx rats.”
Surrogate molecule
No surrogate; clinical vector (Process B) tested in WT and mdx mice
“A 12-week GLP toxicology and biodistribution study (Report No. SR-20-066) evaluated single IV administration of 1.33 × 1014 and 4.01 × 1014 vg/kg ELEVIDYS (manufactured by Process B at Catalent) in 7 to 8 weeks old C57BL/6J WT and mdx mice.”
Study lengthopen answer page →
Longest pivotal study
24 weeks
“A 6-month good laboratory practice (GLP) toxicology and biodistribution study (Report No. SR-19-050) evaluated single IV administration of 1.33 × 1014 and 4.01 × 1014 vg/kg ELEVIDYS”
Pivotal GLP studies
GLP single-dose IV mouse studies: 24-week (WT+mdx), 12-week (WT+mdx, Catalent lot), 13-week neonatal juvenile tox
“A 3-month GLP toxicology study (Report No. SR-20-015) evaluated single IV administration of ELEVIDYS (manufactured by Process B at Catalent) in neonatal C57BL/6J WT mice administered 1.33 × 1014 and 4.01 × 1014 vg/kg at post-natal day 1.”
Route in tox
Single intravenous injection (temporal vein in neonates)
“Dosing Regimen Single administration”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (low-frequency random AAV integration per literature)
“Per the applicant, genotoxicity studies have not been conducted with SRP-9001 because the literature thus far, supports random integration of AAV vector into the host genome at low frequencies”
Carcinogenicity
Not conducted (no cancers in AAV clinical trials; dystrophin possible tumor suppressor)
“Based on the indication of X-linked DMD which occurs primarily in males and lack of concerning findings in the completed toxicology studies, further assessment of developmental and reproductive toxicology, carcinogenicity/tumorigenicity, and genotoxicity are not warranted at this time.”
Reproductive & developmental
Not conducted (male population, no reproductive lesions); neonatal juvenile tox done; low germline signal in testes
“Animal reproductive and developmental toxicity and carcinogenicity studies were not conducted with ELEVIDYS, which is acceptable based on the patient population and lack of ELEVIDYS-related adverse findings in the toxicology studies.”
Safety pharmacology
Not conducted
“There were no safety pharmacology studies performed with SRP-9001.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
NOAEL 4.01x10^14 vg/kg (WT, mdx, neonatal mice); 1.33x10^14 in mdx 12-wk study (hydrocephalus); non-adverse minimal liver findings
“This study identified NOAELs of 4.1 × 1014 vg/kg in WT mice and 1.33 × 1014 vg/kg in mdx mice.”
Risksopen answer page →
Immune & cytokine safety
Anti-AAV antibodies in mice; NHP: capsid/transgene T-cell responses, liver enzymes, anaphylaxis on redosing with rituximab/sirolimus
“increased antibody titers against AAVrh74 vector capsid from Weeks 5 to 12, increased cellular immune response against AAVrh74 vector capsid and micro-dystrophin at Week 2 compared to baseline”
Biodistribution & persistence
Systemic; highest in liver, then adrenal, aorta, heart, muscle; low in testes; shedding in urine/feces/plasma cleared by Day 44
“Systemic ELEVIDYS distribution was observed, with the highest vector levels in the liver, followed by the adrenal gland, aorta, heart, muscle, and esophagus.”
Modality-specific risk
AAV capsid immunity and liver/muscle inflammation; germline transmission; AAV integration (deemed low)
“The potential for the histopathology findings in the liver, heart, and skeletal muscles to be related to test article could not be determined due to the lack of a control group.”