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Precedia/Antibody-drug conjugates/Blenrep/Safety margin

Blenrep: what safety margin did regulators accept?

belantamab mafodotin · BCMA
Check my plan vs. these
Safety margin at NOAEL
Monkey mid-dose ADC AUC approximately equal to human exposure at 2.5 mg/kg (no margin)
“Although ADA formation was evident in monkey studies, the exposures were generally maintained at low and mid-dose animals and were approximately at the same level in mid-dose animals as the recommended human dose of 2.5 mg/kg, based on ADC area under concentration curve (AUC).”
✓ VerifiedEMA assessment report, p. 44Source ↗
NOAEL / key findings
Monkey HNSTD 3 mg/kg; kidney (dose-limiting), liver, lung, testes, bone marrow, cornea (rat), inflammation
“The highest non-severe toxic dose in monkeys was 3 mg/kg and the highest dose tested exceeded the clinical dose by 3.8 and 2.5 -fold (ADC and mAb respectively).”
✓ VerifiedEMA assessment report (EPAR EMEA/H/C/004935/0000, 23 July 2020), p. 44Source ↗

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Safety margin for Blenrep, each with the regulator's own words, the page and a link. Ready to paste into a briefing document or send to your team.

Same question, other ADCs

Adcetris

brentuximab vedotin · CD30
Monkey NOAEL serum exposure ~2 to 3x human exposure at the clinical dose

Besponsa

inotuzumab ozogamicin · CD22
No NOAEL for rat male reproductive effects, seen at ~0.3x human AUC

Datroway

datopotamab deruxtecan · Trop-2
Monkey NOAEL 10 mg/kg (lung, cornea, skin, liver, thymus): margin of exposure 0.25 (below human exposure)

Decnupaz

pivekimab sunirine · CD123
No NOAEL in 13-week monkey study: thymic atrophy at the lowest dose (0.01 mg/kg)

Elahere

mirvetuximab soravtansine · FRα
Monkey NOAEL 4 mg/kg: AUC margin 0.09 (AUC0-24 vs AUCtau) to 0.57 (AUC0-∞)

Enhertu

fam-trastuzumab deruxtecan · HER2
Monkey 30 mg/kg (3-month study) ≥7x human AUC at 5.4 mg/kg

Kadcyla

ado-trastuzumab emtansine · HER2
Monkey HNSTD 10 mg/kg (2040 µg DM1/m2) approximately equivalent to the clinical dose

Padcev

enfortumab vedotin · Nectin-4
Monkey ~3-fold and rat (MTD) ~2-fold human systemic exposure at recommended dose

Tivdak

tisotumab vedotin · Tissue factor
Monkey HNSTD 3 mg/kg ~1.35-2.56x human exposure (Cmax and AUC)

Trodelvy

sacituzumab govitecan · Trop-2
Monkey NOAEL/HNSTD 50 mg/kg: 6.4x (total antibody), 4.6x (total SN-38), 3.1x (free SN-38) human exposure at 10 mg/kg

Zynlonta

loncastuximab tesirine · CD19
Monkey 0.3 mg/kg ~3x human AUC at MRHD 0.15 mg/kg

Emrelis

telisotuzumab vedotin · c-Met
Not stated in public reviews

Mylotarg

gemtuzumab ozogamicin · CD33
Not stated in public reviews

Polivy

polatuzumab vedotin · CD79b
Not stated in public reviews

Summary across all 15 ADCs →