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Atlas/Oligonucleotides/Spinraza/First dose

Spinraza: how was the first human dose set?

nusinersen · SMN2 (ASO)
Check my plan vs. these
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
Monkey neurotoxicity NOAEL 0.3 mg/dose; hippocampal neuronal vacuolation/necrosis; no CSF-based safety margin
“The no-effect dose (0.3 mg) for neurotoxicity in the 53-week monkey study was associated with csf levels (12 ng/mL) generally less than that in SMA patients (7-35 ng/mL); therefore, there is no safety margin based on csf levels.”
✓ VerifiedFDA pharmacology/toxicology review, p. 89Source ↗

Same question, other oligonucleotides

Kynamro

mipomersen · APOB (ASO)
Applicant estimated safe starting dose from nonclinical results; method not specified

Zanvastro

zilganersen · GFAP (ASO)
Starting-dose rationale not stated; FDA capped clinical IT dose at 25 mg (~1/10 mouse/monkey NOAEL), later 50 mg Q12W

Amondys 45

casimersen · DMD exon 45 (PMO)
Not stated in public reviews

Amvuttra

vutrisiran · TTR (siRNA)
Not stated in public reviews

Dawnzera

donidalorsen · Prekallikrein / KLKB1 (ASO)
Not stated in public reviews

Exondys 51

eteplirsen · DMD exon 51 (PMO)
Not stated in public reviews

Givlaari

givosiran · ALAS1 (siRNA)
Not stated in public reviews

Izervay

avacincaptad pegol · C5 (aptamer)
Not stated in public reviews

Leqvio

inclisiran · PCSK9 (siRNA)
Not stated in public reviews

Macugen

pegaptanib · VEGF-165 (aptamer)
Not stated in public reviews

Onpattro

patisiran · TTR (siRNA)
Not stated in public reviews

Oxlumo

lumasiran · HAO1 (siRNA)
Not stated in public reviews

Qalsody

tofersen · SOD1 (ASO)
Not stated in public reviews

Qfitlia

fitusiran · Antithrombin / SERPINC1 (siRNA)
Not stated in public reviews

Redemplo

plozasiran · APOC3 (siRNA)
Not stated in public reviews

Rivfloza

nedosiran · LDHA (siRNA)
Not stated in public reviews

Rytelo

imetelstat · Telomerase (oligo)
Not stated in public reviews

Tegsedi

inotersen · TTR (ASO)
Not stated in public reviews

Tryngolza

olezarsen · APOC3 (ASO)
Not stated in public reviews

Viltepso

viltolarsen · DMD exon 53 (PMO)
Not stated in public reviews

Vyondys 53

golodirsen · DMD exon 53 (PMO)
Not stated in public reviews

Wainua

eplontersen · TTR (ASO)
Not stated in public reviews

Waylivra

volanesorsen · APOC3 (ASO)
Not stated in public reviews

Summary across all 24 oligonucleotides →