Allocation of talimogene laherparepvec (Imlygic®) and JS1/34.5-/47-/mGM-CSF to risk group 1

Human alpha herpesvirus 1 (also known as herpes simplex virus 1, HSV-1) is a globally distributed obligate pathogen of humans. However, other species such as rabbits and rodents can also be infected experimentally. The virus, with a double-stranded DNA genome, is usually transmitted in childhood or through sexual contact in young adults. Infection occurs through direct contact, but transmission via droplets is also possible. After the initial infection, the virus remains latent in neuronal cells or ganglia and can be reactivated. Common clinical symptoms of HSV-1 infection include infections of the mucous membranes, other skin areas (e.g., the fingers), the eyes, and the genitals. In rare cases, severe neurological damage can occur after HSV-1 replication in the brain. HSV-1 has been classified as risk group 2 by the Central Committee for Genetic Engineering (ZKBS) as a donor and recipient organism for genetic engineering work.

The statement can be accessed under the reference number 45242.0134.

Talimogene laherparepvec (JS1/ICP34.5-/ICP47-/hGM-CSF) is based on the HSV-1 strain JS1, which was isolated from a cold sore swab of an otherwise healthy individual. Talimogene laherparepvec is attenuated by various gene deletions and replicates almost exclusively in tumor cells. For clinical use, the gene for human granulocyte-macrophage colony-stimulating factor (hGM-CSF) was inserted into the genome of talimogene laherparepvec. hGM-CSF is involved in the proliferation and differentiation of granulocyte and macrophage precursor cells and is approved as a drug under the name Leukine®. Talimogene laherparepvec is genetically stable; reversion to the more virulent wild type is considered very unlikely. JS1/34.5-/47-/mGM-CSF is a variant of talimogene laherparepvec that contains the murine variant of this gene (mGM-CSF) instead of human GM-CSF and was developed to study the effect of talimogene laherparepvec in mice.

In December 2015, talimogene laherparepvec was approved in the EU under the name IMLYGIC® for the treatment of melanoma in adults. In preclinical studies, talimogene laherparepvec was previously shown to be safe when administered to mice, rats, and dogs at doses up to 60 times the human dose. Some of the preclinical data were collected using JS1/34.5-/47-/mGM-CSF in mice. Clinical studies showed that talimogene laherparepvec was generally well tolerated. Common side effects of treatment with talimogene laherparepvec included nausea, vomiting, diarrhea, fever, fatigue, influenza-like symptoms, pain or reactions at the injection site, and muscle pain. Rarely, severe side effects have been reported, including cellulitis, glomerulonephritis, vasculitis, pneumonitis, and venous thrombosis. The recommendation can be accessed under the reference number 45242.0134.