Entolimod Medicine 13 December 2018 Extended indication Acute radiation syndrome Therapeutic value No judgement Total cost Registration phase Withdrawn Product Active substance Entolimod Domain Oncology and Hematology Reason of inclusion New medicine (specialité) Main indication Oncology other Extended indication Acute radiation syndrome Current proprietary name Already available biosimilars / generics Proprietary name Entolimod TMC Manufacturer TMC Portfolio holder Mechanism of action Unknown Route of administration Intramuscular Therapeutical formulation Injection Budgetting framework Intermural (MSZ) Centre of expertise Additional remarks Recombinant protein that acts as an agonist of toll-like receptor 5 (TLR5). Entolimod activation of TLR5 triggers NF-kB signaling, mobilizing an innate immune response. Registration Registration route Centralised (EMA) Type of trajectory Normal trajectory Particularity Unknown ATMP Unknown Submission date November 2017 Expected Registration Orphan drug Yes Registration phase Withdrawn Reimbursement Medicine sluice Additional remarks Registratieaanvraag ingetrokken in september 2018. EMA: "Based on the review of the data, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Entolimod TMC could not have been approved to reduce the risk of death following exposure to potentially lethal amounts of radiation. The CHMP’s main concern was that there was insufficient evidence from studies, including the macaque study, to determine the effects of the medicine in humans and how it should be used. In addition, there were questions about whether the company had sufficient measures in place to ensure the manufacturing of Entolimod TMC was properly controlled. Therefore, at the time of the withdrawal, the CHMP was of the opinion that the benefits of Entolimod TMC did not outweigh its risks" Therapeutic value Current treatment options Geen Therapeutic value No judgement This assessment does not indicate any potential inclusion in the package. Substantiation Duration of treatment Frequency of administration Dosage per administration 0,4-0,6 μg/kg References Krivokrysenko et al. Predicting a human efficacious dose range for entolimod (CBLB502) based on biomarkers of its anti-radiation efficacy. Chemical and Biological Defense Science and Technology Conference, 2015. Additional remarks Eenmalige injectie Expected patient volume per year Patient volume < 17 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References EMA Additional remarks EMA orphan designation: "less than 0.01 in 10,000 people in the European Union (EU)." Voor Nederland zou dit uitkomen op 17 patienten per 17M inwoners. Expected cost per patient per year Cost References Additional remarks Potential total cost per year Total cost Total cost for sluice Additional remarks Off label use Off label use Unknown Indications off label use References Additional remarks Indication extension Indication extensions Yes Indication extensions Solide tumoren, vaccin adjuvant. References Additional remarks Een mogelijk probleem bij de indicatie-uitbreiding voor solide tumoren is dat de stralenbescherming die als het werkt, ook op de tumor werkt. Op dit aspect zijn de trials niet gericht. De werkgroep verwacht dat het gebruik van entolimod voor deze indicatie dan ook laag zal zijn. Other information Additional remarks