The drug works by replicating in cancer cells, causing them to burst; it was also designed to stimulate an immune response against the patients cancer, which has been demonstrated by multiple pieces of data, including regression of tumors which have not been injected with talimogene laherparepvec.The drug was created and initially developed by BioVex, Inc. and was continued by Amgen, which acquired BioVex in 2011. It was one of the first oncolytic immunotherapy approved globally; it was approved in the US in October 2015 and approved in Europe in December 2015. Medical uses
Talimogene laherparepvec is delivered by injecting it directly into tumors, thereby creating a systemic anti-tumor immune response.In the US, talimogene laherparepvec is FDA approved to treat Stage IIIb-IVM1c melanoma patients for whom surgical intervention is not appropriate and with tumors which can be directly injected; the EMA approved population in Europe is for Stage IIIb-IVM1a.Talimogene laherparepvec has been shown to extend survival in patients with Stage IIIb-IVM1a melanoma and patients who have not received prior systemic therapy for melanoma. Adverse effects
Around half of people treated with talimogene laherparepvec in clinical trials experienced fatigue and chills; around 40% had fever, around 35% had nausea, and around 30% had flu-like symptoms as well as pain at the injection site. The reactions were mild to moderate in severity; 2% of people had severe reactions and these were generally cellulitis.More than 10% of people had edema, headache, cough, vomiting, diarrhea, constipation, muscle pain, or joint pain.
Between 1% and 10% developed cold sores, pain or infection in the lesion, anemia, immune mediated events (like vasculitis, pneumonia, worsening psoriasis, glomerulonephritis and vitiligo ), dehydration, confusion, anxiety, depression, dizziness, insomnia, ear pain, fast heart beating, deep vein thrombosis, high blood pressure, flushing, shortness of breath when exercising, sore throat, symptoms of the common cold, stomach pain, back pain, groin pain, weight loss, or oozing from the injection site. Pharmacology
Talimogene laherparepvec is taken up by normal cells and cancer cells like the wild type herpes simplex virus, it is cleared in the same way. Mechanism
Talimogene laherparepvec directly destroys the cancer cells it infects, inducing a systemic immune response against the patients cancer.The virus invades both cancerous and healthy cells, but it cannot productively replicate in healthy tissue because it lacks Infected cell protein 34.5 (ICP34.5). When cells are infected with a virus they shut down and die, but ICP34.5 blocks this stress response, allowing the virus to hijack the cells translation machinery to replicate itself. A herpesvirus lacking the gene coding for ICP34.5 cannot replicate in normal tissue. However, in many cancer cells the stress response is already disrupted, so a virus lacking ICP34.5 can still replicate in tumors. After the virus has replicated many times, the cell swells and finally bursts, killing the cell and releasing the copies of the virus, which can then infect nearby cells.While talimogene laherparepvec is using the cells translation machinery to replicate, it also uses it to make the cell create GM-CSF.