Registration Dossier

Administrative data

Endpoint:
carcinogenicity, other
Remarks:
subcutaneous injections
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Justification for type of information:
The information has been assessed and approved by the European Medicines Agency

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2014

Materials and methods

Principles of method if other than guideline:
Carcinogenicty data generated according to the requirement for approval of medicines i.e. 2-years carcinogenicity studies in rats and mice and an additional study in monkeys

Test material

Specific details on test material used for the study:
liraglutide (API)

Test animals

Species:
other: rats and mice and monkeys

Administration / exposure

Route of administration:
subcutaneous

Results and discussion

Applicant's summary and conclusion

Conclusions:
Thyroid C-cell tumours have been observed in carcinogenicity studies using subcurtaneosu administration of liraglutide to mice and rats caused by a GLP1 receptor-mediated mechanism. As rodents are shown to be particularly sensitive to this type of tumours and as monkeys did not develop these tumors the fndings are considered of limited relevance to humans.
When using a read-across approach to liraglutide precursor the data is not considered conslusive and not sufficient for a cancer classificatioon according to the CLP criteria.
Executive summary:

Non-lethal thyroid C-cell tumours were seen in 2 year carcinogenicity studies in rats and mice using subcutaneous administration. In rats, a no observed adverse effect level (NOAEL) was not observed. These tumours were not seen in monkeys treated for 20 months. These findings in rodents are caused by a nongenotoxic, specific GLP1 receptor-mediated mechanism to which rodents are particularly sensitive. The relevance for humans is likely to be low but cannot be completely excluded. No other treatment-related tumours have been found.