Anti-TSH receptor-mediated thyroid disease (Graves´ disease)

In Graves´ disease, auto-antibodies are directed against thyroid-stimulating hormone (TSH) receptors in the thyroid gland, which they activate like naturally occurring TSH. This mechanism leads to a chronic excess stimulation of these important regulatory receptors and consecutive hyperthyroidism.

Novel cyclic peptides effectively treat the auto-antibody-mediated propagation of hyperthyroidism. They reduce stimulatory antibodies by immune interference. In disease models, the cyclic peptides successfully improved goiters (thyroid enlargements) and hyperthyroidism and also cured eye symptoms (“auto-immune orbitopathy”) which frequently occur in this condition and are especially hard to treat, as recently published in the scientific journal “Thyroid” (Faßbender et al., Thyroid 2019; 29(2):258-267). Further preclinical investigations including a battery of high-dose safety tests have not revealed any safety issues, lack of immunogenicity, and favourable pharmacokinetic parameters. Submission of all documents (including investigator´s brochure and IMPD) to the European Medicine Agency´s (EMA) portal and BfArM has resulted in the confirmation that a first in man clinical trial is principally deemed possible by regulatory authorities, and can be started once final fill and finish of the existing good manufacturing practice (GMP)-compliant batch of TSHR peptide has been completed. This milestone corresponds to the US Food and Drug Administration´s investigational new drug (IND) status.