WEST HAVEN, CONNECTICUT -- April 22, 2013 -- NanoViricides, Inc. (OTC BB: NNVC) (the "Company") said it anticipates that the oral and injectable FluCide™ drug candidates would be effective against the novel H7N9 strain that has caused human fatalities in China in recent months.
Both the injectable FluCide drug for use in severely ill patients with influenza, and the oral FluCide drug for less sick out-patients bear a virus-binding ligand that mimics sialic acid. Moreover, this ligand is capable of substituting for both the mammalian form (sialyl-alpha2,6-gal-) or the avian form (sialyl-alpha2,3-gal-). Since the novel H7N9 (2013) virus is transitioning from avian to human host, the dual biomimetic capability of our FluCide ligand should have a favorable impact.
CDC, and scientists from China and Japan have reported, based on the genetic structure of the novel H7N9 virus, that this virus is likely to bind well with the mammalian form of sialic acid. This virus is also reported to bear other mutations that enable it to infect mammalian hosts effectively. Existing H7-vaccine viruses are not well matched to this novel H7N9 virus, and new vaccine development will take some time. This H7N9 is resistant to amantadine and rimantadine, as are most US and European Influenza A virus strains. It is suggested to be susceptible to neuraminidase inhibitors such as oseltamivir (Tamiflu®) and zanamivir (Relenza®), but certain mutations suggest resistance to these drugs. CDC authors Dr. Uyeki and Dr. Cox note that clinical research is urgently needed on new antiviral agents, including drugs with different mechanisms of action.
Both the oral and the injectable FluCide drug candidates have shown extremely high effectiveness in highly lethal mouse models of two distinctly different influenza A virus infections, viz. H1N1 and H3N2, indicating that FluCide drugs indeed have a broad-spectrum effect against influenza viruses, irrespective of the subtype or strain.
In these highly lethal studies, FluCide drug candidates have achieved complete survival (22+ days), while in contrast, Tamiflu® (oseltamivir) resulted in only 8-9 days survival, and the untreated animals die within 5 days. The FluCide oral and injectable drug candidates also protected the lungs of the animals much better than did oseltamivir, indicating a clear benefit. The protection from influenza virus was clearly reflected in the strong increase in survival time in the FluCide-treated animals as compared to oseltamivir. The FluCide drugs were seen to be far superior to Tamiflu also in terms of viral load reduction. The FluCide drugs were extremely well tolerated, in contrast to oseltamivir. No dose-limiting side effects have been seen for our FluCide candidates as yet, indicating that in a severely ill patient, the dosage of FluCide can be increased even further. In these animal studies, the mouse serves only as a “test tube” and FluCide is designed to attack the virus (not the host). Thus the results are expected to correlate well with the impending human clinical studies.
Binding to sialic acid on the cell surface is a completely conserved property of all influenza viruses. The avian influenza viruses tend to prefer binding to the a-2,3- variant of sialic acid, whereas those causing disease in humans tend to prefer binding to the a-2,6- variant. Pigs and some other species serve as “mixing species” where both the avian and mammalian viruses can grow, and further, avian viruses can mutate to mammalian viruses.
The Company has previously reported that it is enabling cGMP production of the FluCide drug candidates in the near future. The Company reports further that the design phase of the cGMP clinical batch production and laboratory facilities is completed and bidding phase for subcontracts has begun.
The Company has held a pre-IND meeting with the US FDA at the end of March, 2012, for the injectable FluCide drug candidate, and has been working on the IND enabling studies for this drug. The Company has previously reported that it has successfully developed the very first orally bio-effective nanomedicine. This development has added the oral FluCide as an additional drug candidate to the Company’s pipeline. Oral anti-influenza drugs have estimated market size of $4B to $7B at present, which could expand substantially if a highly effective anti-influenza drug such as FluCide is developed.
ref: 1. Uyeki TM, Cox NJ. Global Concerns Regarding Novel Influenza A (H7N9) Virus Infections. N Engl J Med. 2013; doi:10.1056/NEJMp1304661. 11 April, 2013. 2. Kageyama T, Fujisaki S, Takashita E et al. Genetic analysis of novel avian A (H7N9) influenza viruses isolated from patients in China, February to April 2013. Eurosurveillance 2013; 18(15). 3. Gao R, Cao B, Hu Y, et al. Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus. N Engl J Med. 2013; doi:10.1056/1304459.