ChemRar Group is announcing a successful completion of a safety evaluation of a new-generation drug for the treatment of all influenza virus forms with a broad spectrum of action
ChemRar Group (ChemRar) has announced a successful completion of a safety and tolerability trial of a fundamentally new oral candidate drug АВ5080 (AV5080) with a wide range of anti-influenza activity, including the treatment of influenza type A and type B strains resistant to any existing first- and second-generation drugs.
The pharmacokinetics and safety of АВ5080 was evaluated in healthy volunteers, the drug was administrated at doses of 30 mg, 80 mg and 160 mg per day. The daily average concentrations during the five-day course were close to or significantly exceeded the ЕС50 for the inhibition of neuraminidases obtained for 10 influenza virus strains even at the dose of 30 mg. The study results demonstrated safety and good tolerability, no adverse events were observed.
Because of the ability of the influenza virus to mutate rapidly, leading to a risk of increased pathogenicity and severity of disease, the human body cannot produce absolute immunity to the pathogen. According to WHO, during flu and related epidemics up to 5 million people get ill, of whom 500 thousand people (most of them older than 65 years) die each year, in some years the number of deaths may reach a million. In addition to vaccines that are the primary means of preventing influenza infection, targeted therapy drugs are considered promising therapeutic agents against influenza virus types A and B.
The first generation of synthetic drugs for the treatment of influenza was ion channel blockers targeted against the M2 protein of influenza type A, which include amantadine and rimantadine. They however are not effective against influenza type B. Their use is accompanied by side effects and a risk of rapid development of resistant influenza virus forms.
The second-generation drugs currently include neuraminidase inhibitors, including Tamiflu (oseltamivir phosphate) for oral administration, inhalation drug zanamivir and intravenous peramivir. These drugs are effective against influenza type A and B. They prevent new viral particle release from infected cells and their spread throughout the body. However, Tamiflu has low efficacy in the treatment of many pandemic influenza strains and is characterized by the development of resistant forms. The disadvantage of zanamivir and peramivir is, correspondingly, the inhalation and intravenous methods of drug delivery.
A new oral second-generation drug АВ5080 is effective against influenza type A and B strains resistant to the existing first- and second-generation drugs, including rimantadine resistant (RR) and oseltamivir resistant (OR) strains.
Experiments with the use of selection pressure have demonstrated that the mutational profile of the virus surviving in the presence of АВ5080 had a much lower number of single nucleotide mutations than in the presence of oseltamivir or zanamivir. АВ5080 can suppress a much broader range of mutants that are resistant to the existing drugs, in particular, АВ5080 effectively inhibits neuraminidases with the ЕС50 in the range from 70 pM to 6.65 nM obtained from 12 different influenza strains.
In 2017 ChemRar Group continues the clinical trial program to evaluate the efficacy of АВ5080. The trials will be conducted in influenza-infected patients. In case of successful completion of clinical trials, АВ5080 may become the first innovative oral drug in Russia for treatment of influenza type A and B strains resistant to the existing first- and second-generation drugs.
The АВ5080 drug development is supported by the Ministry of Industry and Trade of the Russian Federation as part of the Federal Program Development of the Pharmaceutical and Medical Industries of the Russian Federation up to 2020 and Beyond.
About ChemRar Group
ChemRar Group unites R&D service and investment companies in the field of innovative pharmaceuticals for the development and commercialization of innovative medicines, diagnostics, preventive care and new treatments of life-threatening diseases in Russia and abroad. www.en.chemrar.ru