NanoViricides Looks to Revolutionize How We Approach Flu. Can They Do So, and Justify the Financial Burden?
During an interview with OneMedPlace, President and Chairman of NanoViricides (NNVC) Anil Diwan summed up the influenza treatment market in just a few words.
“It’s like trying to hit a moving target”.
Looking at the estimated $4.5-7 billion influenza market that encompasses both human and avian strains of numerous types – such as H1N1 (Bird Flu) or the recent H7N9 strain – Diwan’s “moving target” statement makes sense: the genetic structure of the influenza virus constantly mutates, thus making an effective, lasting vaccine is extremely difficult, if not impossible.
Influenza, therefore, is considered one of the toughest, riskiest, and costliest subsectors of healthcare. Still, as evidenced by the 30 deaths in China caused by H7N9 – influenza represents a significant unmet medical need.
Dr. Diwan further discussed logistical issues – that influenza vaccines in particular rely heavily on highly specialized antibodies and tight quality control standards for manufacturing. As these antibodies are highly specific to a particular strain, tailoring an effective vaccine to a specific strain is a very expensive – and some would argue, quixotic challenge – that brings minimal benefit and renders many of the vaccines useless.
For example, a vaccine being developed must demonstrate efficacy against four “type zero” strains and four “type one” strains. According to Dr. Diwan, this is easier said than done: each type zero and type one is different, and thus the likelihood to demonstrate success among all eight is rare.
Dr. Diwan estimated the cost of influenza vaccine R&D and production to be between $1.7-2 BN per candidate over 10 years.
“If you are lucky, one passes”, Dr. Diwan said, referring to one of only two commercially available influenza treatments, but more importantly, to the countless failed treatments over the years.
Failed, or ‘useless’ does not simply mean therapies that do not reach market. Many vaccines produced are purchased for government stockpile, and go unused – only 2-3% of vaccines purchased are actually used, according to Dr. Diwan.
Clearly, there exists a need for a new approach that can be more easily adapted to new strains.
Changing Perceptions & Theories Concerning Influenza Treatment
NanoViricides is named after the company’s proprietary flexible Biomimetic Polymer glob that wraps around a virus and traps it, with the virus losing its coat of proteins, needed to bind to a cell. Thus, the virus is neutralized, and effectively destroyed without immune system assistance.
NanoViricides President and Chairman Anil Diwan stated the company’s flagship influenza treatment is based upon the premise that most viruses share the same basic genetic layout, the same way that most cars share the same layout.
NanoViricide’s FluCide is based on a novel mechanism of action wherein the drug micelle is designed to attract and bind itself to the virus via multi-dentate interactions, and then into the virus surface via lipid-lipid interactions with the viral lipid coat. With a mechanism similarity to natural antibodies, in which antibodies bind and cover the virus, FluCide can be designed to have as many as twenty or more virus-binding ligands, uniformly spaced along the chain. The FluCide compound is designed to attack the flu virus to both kill it and protect against future infection, according to company CEO Eugene Seymour.
As discussed earlier, an antibody alone is generally not enough for destruction of the virus. The antibody-coated virus particle or a resulting immuno-precipitate must be engaged by the human immune system in various ways for the virus infection to be controlled and eventually overcome.
In contrast, a Nanoviricide agent is designed to perform its antiviral effect even if the immune system is compromised. Further, antibodies are highly specific to a virus strain, and since influenza virus can mutate rapidly it can escape the antibody. In contrast, the virus-binding ligands on FluCide are chosen to mimic the sialic acid. Binding to sialic acid is an absolutely required first step for any influenza virus to infect a human host.
In effect, FluCide tricks (or “trolls”) the virus into thinking it is a healthy cell.
FluCide is being developed in two forms: the injectable FluCide drug designed to be used in severely ill patients with influenza, and the oral FluCide for less serious out-patients. FluCide consists of a Nano-sized ligand that mimics sialic acid capable of substituting for both the mammalian and avian forms. The company hopes that the dual biomimetic capabilities of the FluCide ligand will have a favorable impact.
Real-life Application
The CDC and scientists from China and Japan reported that the genetic structure of the novel H7N9 virus allows it to bind well with the mammalian form of sialic acid, along with other mutations that enable it to infect mammalian hosts effectively. Since existing H7 type-vaccines are not effective against the novel H7N9 virus, new vaccine development will take time.
It is suggested that the new strain is susceptible to neuraminidase inhibitors such as oseltamivir (Tamiflu) and zanamivir (Relenza), but certain mutations demonstrated resistance to these drugs.
In the interview with OneMedPlace, Dr. Diwan suggested FluCide would not encounter resistance.
Data, Upcoming Trials, and Optimism
The company also believes that by moving away from a vaccine-type approach, treatment can also become far more cost efficient. In an extended trial, FluCide was shown to be 1,500 times more effective than TamiFlu in a lethal animal model.
Dr. Seymour said that further trials of FluCide will take place in Australia because the Australian government reimburses 45 percent of research and development expenses, and also favorable conditions for certifying their drug manufacturing facilities.
A Phase 1 and 2a trial is planned to commence in the fall of 2014, after construction work to expand a leased research lab in Shelton, Connecticut is completed. Dr. Seymour said the timeline on the trials is short: a Phase 1/2a trial involving 24 patients would take about four to six weeks, followed by a Phase 2b trial with 100 patients, which would take about another month, and then a Phase 3 trial with a sample size of about 500 patients would take two more months.
The company plans to seek approval abroad first. However, as Seymour noted, the recent “Pandemic and All-Hazards Preparedness Reauthorization Act of 2012” bill could mean that FluCide’s approval in Australia could lead to marketization in the United States in as little as two years.
“We could have material available in the U.S. for the 2014-2015 flu season.” Dr. Seymour said. “Definitely a year later, we would have a hell of a lot more.”