Cocaine Intoxication / Overdose
Mid-Phase II — Breakthrough Therapy Designation
Awarded Cooperative Agreement Grant from National Institute on Drug Abuse (NIDA)
TNX-1300 (recombinant T172R/G173Q double-mutant cocaine esterase 200 mg, IV solution) is being developed under an Investigational New Drug application (IND) for the treatment of cocaine intoxication. It has been designated a Breakthrough Therapy by the FDA. Currently there is no specific pharmacotherapy indicated for cocaine intoxication, a state characterized by acute agitation, hyperthermia, tachycardia, arrhythmias, and hypertension, with the potential life-threatening sequalae of myocardial infarction, cerebrovascular accident, rhabdomyolysis, respiratory failure, and seizures. Patients are currently managed only by supportive care for the adverse effects of cocaine overdose on the cardiovascular and central nervous systems.
TNX-1300 is a recombinant protein enzyme produced through recombinant DNA technology in a non-disease-producing strain of E. coli bacteria. Cocaine Esterase (CocE) was identified in bacteria (Rhodococcus) that use cocaine as its sole source of carbon and nitrogen and that grow in soil surrounding coca plants.3 The gene encoding CocE was identified, and the protein was extensively characterized.3-6 CocE catalyzes the breakdown of cocaine into metabolite ecgonine methyl ester and benzoic acid. Wild-type CocE is unstable at body temperature, so targeted mutations were introduced in the CocE gene and resulted in the T172R/G173Q double-mutant CocE, which is active for approximately 6 hours at body temperature7. In a Phase 2 study, TNX-1300 at 100 mg or 200 mg IV doses were well tolerated and interrupted cocaine effects after cocaine 50 mg IV challenge.1 TNX-1300 was well tolerated with the most frequently reported adverse events being gastrointestinal disorders (including dry mouth, nausea); nervous systems disorders (including headache, dizziness) and skin and subcutaneous tissue disorders (including hyperhidrosis, dermatitis).
By targeting the cause of cocaine intoxication, rather than the symptoms like other medicines in emergency usage, TNX-1300 may offer significant advantages to the current standard of care for cocaine overdose.