Hemlibra (emicizumab): how was the first human dose set?

Precedia/Multispecific antibodies/Hemlibra/First dose

Hemlibra: how was the first human dose set?

emicizumab · FIXa x FX

First-in-human starting dose

Not stated in public reviews

Why it's blank

The public FDA and EMA reviews of Hemlibra 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 multispecifics

Use pharmacology data (target binding, receptor occupancy, in vitro human cells, PK/PD modelling) to estimate the lowest dose expected to have any biological effect (MABEL) and the active dose (PAD), and, for healthy volunteers, start at an exposure below the PAD unless robustly justified.

“these data should be used to determine the minimal anticipated biological effect level (MABEL) in humans and an estimation of the pharmacologically active dose (PAD) and/or anticipated therapeutic dose range (ATD) in humans.”

✓ VerifiedEMA 2017: Guideline on strategies to identify and mitigate risks for…, p. 11Source ↗

This product's starting point

NOAEL / key findings: NOAEL 30 mg/kg/wk SC (26-week), ~11x clinical AUC; findings limited to injection-site reactions and aPTT shortening (EMA assessment report, p. 35)

Full method, every step sourced →

NOAEL / key findings

NOAEL 30 mg/kg/wk SC (26-week), ~11x clinical AUC; findings limited to injection-site reactions and aPTT shortening

“This is approximately 11-fold above the clinical exposure in a 3 mg/kg QW dosing regimen which is the regimen that is anticipated to yield the highest exposure in patients.”

✓ VerifiedEMA assessment report, p. 35Source ↗

Summary across all 18 multispecifics →

Hemlibra: how was the first human dose set?

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