Nonclinical safety assessment of epigenetic modulatory drugs: Current status and industry perspective.
Regul Toxicol Pharmacol
; 117: 104746, 2020 Nov.
Article
en En
| MEDLINE
| ID: mdl-32911461
ABSTRACT
Pharmaceutic products designed to perturb the function of epigenetic modulators have been approved by regulatory authorities for treatment of advanced cancer. While the predominant effort in epigenetic drug development continues to be in oncology, non-oncology indications are also garnering interest. A survey of pharmaceutical companies was conducted to assess the interest and concerns for developing small molecule direct epigenetic effectors (EEs) as medicines. Survey themes addressed (1) general levels of interest and activity with EEs as therapeutic agents, (2) potential safety concerns, and (3) possible future efforts to develop targeted strategies for nonclinical safety assessment of EEs. Thirteen companies contributed data to the survey. Overall, the survey data indicate the consensus opinion that existing ICH guidelines are effective and appropriate for nonclinical safety assessment activities with EEs. Attention in the framework of study design should, on a case by case basis, be considered for delayed or latent toxicities, carcinogenicity, reproductive toxicity, and the theoretical potential for transgenerational effects. While current guidelines have been appropriate for the nonclinical safety assessments of epigenetic targets, broader experience with a wide range of epigenetic targets will provide information to assess the potential need for new or revised risk assessment strategies for EE drugs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
/
Encuestas y Cuestionarios
/
Epigénesis Genética
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Control de Medicamentos y Narcóticos
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Industria Farmacéutica
Tipo de estudio:
Etiology_studies
/
Guideline
/
Qualitative_research
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Regul Toxicol Pharmacol
Año:
2020
Tipo del documento:
Article