Vitravene (fomivirsen): how was the first human dose set?

Atlas/Oligonucleotides/Vitravene/First dose

Vitravene: how was the first human dose set?

fomivirsen · CMV IE2 mRNA (ASO)

First-in-human starting dose

Not stated in public reviews

Why it's blank

The public FDA and EMA reviews of Vitravene don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.

How it's usually set for oligonucleotides outside oncology

Find the highest dose with no adverse effects (NOAEL) in each animal species, convert it to a human equivalent dose, usually by body surface area, pick the most appropriate species, then divide by a safety factor (default 10) to get the maximum recommended starting dose.

“In general, one should consider using a safety factor of at least 10. The MRSD should be obtained by dividing the HED by the safety factor.”

✓ VerifiedFDA 2005: Estimating the Maximum Safe Starting Dose in Initial Clinical…, p. 7Source ↗

This product's starting point

NOAEL / key findings: Monkey 115 µg intravitreal with triamcinolone: no ocular alterations; transient IOP decrease in 3/6 (FDA review, p. 24)

Full method, every step sourced →

NOAEL / key findings

Monkey 115 µg intravitreal with triamcinolone: no ocular alterations; transient IOP decrease in 3/6

“Group 2 (115 ug of fomivirsen + triamcinolone) or in control animals had no ocular alterations. A transient decrease in IOP was identified in 3/6 Group 2 animals.”

✓ VerifiedFDA review, p. 24Source ↗

Summary across all 28 oligonucleotides →

Vitravene: how was the first human dose set?

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