title: Preclinical safety of a nucleic acid-targeted Helinx compound: a clinical perspective.
abstract: Helinx technology (Cerus Corp, Concord, CA) uses amotosalen HCl (S-59) and ultraviolet A (UVA) light in an ex vivo photochemical treatment (PCT) to inactivate viruses, bacteria, and leukocytes in platelet concentrates while preserving therapeutic function. A comprehensive preclinical safety program was conducted, which included carcinogenicity, single-dose and multiple-dose (up to 13 weeks' duration) toxicity, safety pharmacology (central nervous system [CNS], renal, and cardiovascular), reproductive toxicity, genotoxicity, vein irritation, phototoxicity, and toxicokinetic testing. The results of the toxicokinetic analyses indicated that the test articles provided large multiples of the clinical exposure to S-59, whether the comparison was based on dose, maximum plasma concentration, or area under the concentration-time curve. No specific target organ toxicity, reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS toxicity, electrocardiographic (ECG) effects, and phototoxicity at supraclinical doses. On the basis of the extremely large safety margins, the CNS and ECG observations (at >30,000-fold the expected clinical exposure) as well as the results of genotoxicity and phototoxicity studies are not considered to be of toxicological relevance. The results of an extensive series of studies have thus demonstrated no toxicologically relevant effects of platelets treated with Helinx technology.
authors.affiliation: Department of Preclinical Safety, Cerus Corporation, Concord, CA 94520, USA.
authors.forename: V
authors.initials: V
authors.lastname: Ciaravino
mesh_terms: D000818:Animals; D004247:DNA / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005363:Ficusin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D011564:Furocoumarins; D006801:Humans; D017053:Infection Control / Q000379:methods / Q000592:standards; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D017713:Platelet Transfusion / Q000009:adverse effects / Q000592:standards*; D014466:Ultraviolet Rays
chemical_list: D011564:Furocoumarins; D017319:Photosensitizing Agents; D004247:DNA; C118577:amotosalen; D005363:Ficusin