Rethymic (allogeneic processed thymus tissue): what was done before first-in-human, and what came after?

Precedia/Cell therapy/Rethymic/Tox package

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

allogeneic processed thymus tissue · Allogeneic thymus tissue

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 Rethymic 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 cell therapies

FDA expects preclinical proof-of-concept and toxicology studies to identify active dose levels and support the choice of starting dose and escalation. The 2013 guidance gives no numeric formula or scaling rule for the starting dose.

“Selection of potential starting dose level, dose-escalation schedule, and dosing regimen for clinical trials.”

✓ VerifiedFDA 2013: Preclinical Assessment of Investigational Cellular and Gene Therapy…, p. 7Source ↗

This product's starting point

NOAEL / key findings: No NOAEL; no toxicology studies; dose range from clinical use (FDA pharmacology/toxicology review, p. 2)

Full method, every step sourced →

Longest repeat-dose systemic studies

Longest repeat-dose study and recovery

No repeat-dose study (no nonclinical toxicology studies conducted)

“Per the applicant, based on the acceptable clinical safety profile of RVT-802 and the lack of relevant animal models, no nonclinical toxicology studies with RVT-802 were conducted.”

✓ VerifiedFDA pharmacology/toxicology review, p. 21Source ↗

Pivotal GLP studies

No toxicology studies; pharmacology only (in vitro thymus organ culture, nude rat transplants to 9 months)

“no nonclinical toxicology studies with RVT-802 were conducted.”

✓ VerifiedFDA pharmacology/toxicology review, p. 21Source ↗

DART package

Species: DART

Not conducted; published mouse thymectomy literature reviewed instead

“No DART studies were conducted. To assess the DART potential of RVT-802, the applicant examined published assessments of DART outcomes in mice following thymectomy.”

✓ VerifiedFDA pharmacology/toxicology review, p. 21Source ↗

Reproductive & developmental

Not conducted; published thymectomy literature suggests minimal risk

“No DART studies were conducted.”

✓ VerifiedFDA pharmacology/toxicology review, p. 21Source ↗

PPND / ePPND: when

Not conducted and not indicated

“In vitro or in vivo genotoxicity, carcinogenicity, or developmental and reproductive toxicity studies were not conducted with RETHYMIC, nor were they indicated.”

✓ VerifiedFDA summary basis for approval, p. 12Source ↗

Carcinogenicity

Species: carcinogenicity

Not conducted; published mouse thymus-transplant literature reviewed instead

“No carcinogenicity/tumorigenicity studies were conducted. To assess the carcinogenicity/tumorigenicity potential of RVT-802, the applicant examined published assessments of carcinogenicity outcomes in mice following thymus transplantation.”

✓ VerifiedFDA pharmacology/toxicology review, p. 22Source ↗

Carcinogenicity model

Not conducted; literature on thymus transplantation in tumor-bearing mice reviewed; risk considered minimal

“Although the thymus products administered were not identical to RVT-802 and the studies were conducted in tumor-bearing mice (which does not reflect the clinical scenario), these data combined with the existing clinical safety data for RVT-802, indicate that the risk of carcinogenicity after RVT-802 transplantation in humans appears to be minimal.”

✓ VerifiedFDA pharmacology/toxicology review, p. 22Source ↗

Carcinogenicity timing

Not required: carcinogenicity studies not conducted and not indicated

“In vitro or in vivo genotoxicity, carcinogenicity, or developmental and reproductive toxicity studies were not conducted with RETHYMIC, nor were they indicated.”

✓ VerifiedFDA summary basis for approval, p. 12Source ↗

Summary across all 27 cell therapies →

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

Before first-in-human

Longest repeat-dose systemic studies

DART package

Carcinogenicity

Email me this as a cited memo

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