Decnupaz (pivekimab sunirine): what was done before first-in-human, and what came after?

Precedia/Antibody-drug conjugates/Decnupaz/Tox package

Decnupaz: what was done before first-in-human, and what came after?

pivekimab sunirine · CD123

Before first-in-human

First-in-human: where

Not stated in public reviews

Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.

Repeat-dose tox before first-in-human

Not stated in public reviews

Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.

First-in-human starting dose

Not stated in public reviews

Why it's blank

The public FDA and EMA reviews of Decnupaz 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 ADCs

ADCs with cytotoxic payloads follow the S9 rules (1/10 STD10 or 1/6 HNSTD of the ADC, scaled by body surface area). For immune agonists, a MABEL-based start dose should be considered instead.

“For example, for cytotoxic payloads, the starting clinical dose can be determined using either 1/10th the Severely Toxic Dose (STD) in 10% of animals (STD10) in rodents or 1/6th the Highest Non- Severely Toxic Dose (HNSTD) in non-rodents, for the ADC based on body surface area, depending on which is the most appropriate and/or sensitive species.”

✓ VerifiedICH 2018: ICH S9 Guideline: Nonclinical Evaluation for Anticancer…, p. 15Source ↗

This product's starting point

NOAEL / key findings: FDA: no NOAEL in 13-week (thymic atrophy ≥0.01 mg/kg); single-dose max nonlethal 0.4 mg/kg; marrow, GI, skin, thymus (FDA multi-discipline review, p. 61)

Full method, every step sourced →

Longest repeat-dose systemic studies

Longest repeat-dose study and recovery

13-week GLP cynomolgus monkey IV study (every 3 weeks, five doses) with 8-week recovery

“a 13-week repeat-dose GLP study with pivekimab sunirine in cynomolgus monkeys (0, 0.01, 0.03, or 0.1 mg/kg administered once every three weeks for five doses) with an 8-week recovery period.”

✓ VerifiedFDA multi-discipline review, p. 42Source ↗

Pivotal GLP studies

GLP IV cyno single-dose (0.1-0.6 mg/kg, 28-day recovery) and 13-week Q3W (0.01-0.1 mg/kg, 8-week recovery); FGN849 rat studies

“The toxicity of PVEK has been characterized in single- and repeat-dose studies (up to 13 weeks in duration).”

✓ VerifiedFDA multi-discipline review, p. 50Source ↗

DART package

Species: DART

Not conducted (ICH S9 and FDA feedback)

“No reproductive and developmental studies have been conducted with PVEK, in accordance with ICH S9 and FDA feedback (Reference ID: 4704103).”