NanoViricides Inc. (NNVC)

[changes_iv]

What happens after NanoViricides Submits (Jun 10, 2013) DengueCide™ Orphan Drug Designation Application to the US FDA for dengue and dengue hemorrhagic fever?

from Orphan Drug Designation
by Jeff Fritsch Debra Lewis Erica McNeilly Henry (Chip) Startzman
FDA Office of Orphan Products Development

NNVC is sent a letter acknowledging receipt of the application.

Reviewed by reviewer - designation Team Leader - OOPD director.

Expect less than 90 days to decision (for DengueCide® that is September 2013). A negative decision can always be readdressed.

Roughly 60-70% of applications result in granting orphan drug designation status.

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The Orphan Drug Designation program provides orphan status to drugs and biologics[1] which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug.

Orphan drugs generally follow the same regulatory development path as any other pharmaceutical product, in which testing focuses on:

1)pharmacokinetics - discover the fate of a drug from the moment that it is administered up to the point at which it is completely eliminated from the body

*** I could not find info on this

2)pharmacodynamics - study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect

A nanoviricide is constructed by chemically attaching virus-binding ligands to a polymeric micelle. The biomimetic ligands tend to have poor energies of interaction with the virus particle per ligand, yet a large number of ligands enable a successful interaction with the virus particle. Additionally, the nanoviricide competes with cells for binding to the virus particle, and must provide a substantially more efficient interaction than the cell-virus interaction, in order to achieve a therapeutic effect.

3)dosing - generally applies to feeding chemicals or medicines in small quantities into a process fluid or to a living being at intervals or to atmosphere at intervals to give sufficient time for the chemical or medicine to react or show the results

*** I could not find info on this

4)stability - A drug must remain potent and safe long after it leaves a manufacturing facility. Ensuring this safety requires a range of technologies and applications.

*** I could not find info on this

5)safety - companies must show evidence of their compound’s biological activity and provide data indicating that the drug is reasonably safe and effective before initial administration

from Dr. Diwan --- The nanoviricide also must be able to exercise its effect in the biological matrix, be it in the bloodstream, plasma, mucosa, or other extracellular spaces. Further, it should have minimal undesirable interaction with the matrix and host cells so that sufficient material is available for clearing out a fulminant viral infection from a patient's body. In addition, the nanoviricide needs to be able to distribute itself within the body, across various barriers, so that it can reach the spaces where the virus particles are present. NanoViricides, Inc. has demonstrated that highly effective antiviral treatments can be created against a large number of viruses, despite these design challenges.

6)efficacy - DengueCide has shown very high effectiveness in animal models of dengue virus infection and also in cell culture studies of dengue virus infection.

However, some statistical burdens are lessened in an effort to maintain development momentum. For example, orphan drug regulations generally acknowledge the fact that it may not be possible to test 1,000 patients in a phase III clinical trial, as fewer than that number may be afflicted with the disease in question.

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THE SCIENCE OF HOPE:
The need, the challenges and three proven strategies
for successful orphan drug development - from Premier-Research

Advantages of Orphan Drug Development

Developmental drivers such as government incentives, shorter development timelines and high rates of regulatory approval are making orphan drug development as economically viable as non-orphan drug development, even though the patient pool is smaller.

The time from Phase II to market is often shorter for orphan drugs due to shorter and smaller clinical trials and FDA Fast Track designation.

Once a compound has been granted orphan designation, the odds for approval are high (82%) compared to traditional drugs (35%).

Of note, orphan designation for the drug in the orphan indication is maintained regardless of follow-on indications. As a result, one model for development is based on lead development of a compound with a relatively quick-to-market orphan indication, followed by consideration of expansion to other indications. Orphan drugs also experience significant competitive advantage in being first to market. Recent research suggests that the higher
pricing, increased market share, lower marketing costs, longer exclusivity period and faster uptake of orphan drugs offset the smaller patient pool. For example, Soliris® (Alexion Pharmaceuticals), indicated for treatment of paroxysmal nocturnal hemoglobinuria (PNH), generated $541 million in sales in 2010, despite the fact that there are only an estimated 4,000-6,000 patients in the U.S. with PNH.

In Puerto Rico, U.S. territory: The most recent island-wide epidemic occurred in 2007, when more than 10,000 cases were diagnosed

The revenue-generating potential of orphan drugs is compounded in cases where drugs have multiple orphan disease indications, or go on to gain approval for larger, non-orphan disease indications. In addition, a high number of orphan drugs are biologics[1], which
are less likely to have generic equivalents, prolonging their value to sponsors, even after patent expiration.

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WEST HAVEN, CONNECTICUT -- June 10, 2013 -- NanoViricides, Inc. (OTC BB: NNVC) (the "Company") announced today that it has filed an Orphan Drug application with the Office of Orphan Product Development (OOPD) of the US FDA for DengueCide™, its drug candidate for the treatment of dengue and dengue hemorrhagic fever.

The Company previously engaged the consulting firm Cote´ Orphan Consulting (COC), headed by Dr. Tim Cote´, to assist with the orphan drug application. The Company, in consultation with COC, has determined that its current lead DengueCide™ drug candidate is eligible for orphan drug status application in the USA.

Tim Cote´, MD, MPH, was the Director of the Office of Orphan Product Development (OOPD) at the FDA, from 2007 to 2011. In this role heading OOPD at the Agency, he was responsible for the implementation of the Orphan Drug Act, a system of grants and drug development incentives designed to create therapies for 6,000+ rare diseases. After leaving the US FDA, Dr. Cote´ served as the Chief Medical Officer (CMO), National Organization for Rare Disorders (NORD), Washington, DC. He has held several other illustrious positions with increasing responsibilities during his career, including CDC Country Director for Rwanda, Senior Research Investigator in the Viral Epidemiology Branch of the National Cancer Institute, and Branch Chief, Therapeutics and Blood Safety, CBER, FDA. In addition to his role as the Principal at COC, Dr. Cote´ is currently Professor of Regulatory Practice at the Keck Graduate Center, Claremont, CA.
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I am confident we are going to get FDA approval. My reasons?

1)The Cides "...are agnostic as to the host.” and the efficacy of DengueCide* is unprecedented**. Feel free to add others, if you have the information.

* DengueCide™, our broad-spectrum drug candidate against all four types of dengue, has led to survival of 50% of mice in an ADE (antibody-dependent-enhancement) mouse model of dengue infection, clinically relevant for the high fatality rate dengue DHF/DSS manifestations.

Antibody-dependent enhancement (ADE) - occurs when non-neutralising antiviral antibodies enhance viral entry into host cells, leading to increased infectivity in the host cells. Some cells do not have the usual receptors on their surfaces that viruses use to gain entry. The antibodies bind to antibody Fc receptors that some of these cells have in their plasma membrane. The viruses bind to the antigen binding site at the other end of the antibody. ADE is common in cells cultured in the laboratory, but rarely occurs in vivo except for dengue virus. This virus can use this mechanism to infect human macrophages, causing a normally mild viral infection to become life threatening.

** DengueCide is a nanoviricide® that has shown very high effectiveness in animal models of dengue virus infection and also in cell culture studies of dengue virus infection. These animal studies as well as cell culture studies were conducted in the laboratory of Dr. Eva Harris, Professor of Public Health and Infectious Diseases at the University of California, Berkeley. Prof. Harris found that the special laboratory mouse strain AG129 infected with a dengue virus in a lethal challenge ADE-simulation protocol, when left untreated, suffered a 100% fatality rate. In contrast, in the same study, animals treated with NanoViricides' DengueCide achieved an unprecedented 50% survival rate.

2)Barring influence of "Big Pharma" , over the FDA, against us, we should get approval. But why would they be against us? For example, according to Mayo Clinic, "No specific treatment for dengue fever exists. Your doctor may recommend that you drink plenty of fluids to avoid dehydration from vomiting and high fever. Acetaminophen (Tylenol, others) can alleviate pain and reduce fever. Avoid pain relievers that can increase bleeding complications — such as aspirin, ibuprofen (Advil, Motrin, others) and naproxen sodium (Aleve, others)." Of the four viruses of Dengue, Nanoviricides picked the two worse (DHF***/DSS***) and there is currently no drug or specific treatment for them. Therefore "Big Pharma" doesn't have a competing drug or vaccine and to me this eliminates the possibility of their involvement.

*** When a person is exposed to dengue for the first time, the disease usually is not severe. When the same person is later infected by a different dengue serotype, the body produces antibodies against the previous dengue serotype. The new dengue virus uses these antibodies to infect more cells, thus leading to severe dengue disease. Such a secondary infection may lead to dengue hemorrhagic fever or dengue shock syndrome with high fatality rates. The ADE phenomenon has made development of vaccines and antibody therapeutics against Dengue a tremendous challenge. A vaccine works by creating antibodies against the included serotypes.

3)A very competent and reputable group, Cote´ Orphan Consulting (COC), was in charge of gathering all data, results (there is info about DengueCide-FDA requirements I could not find but I feel confident they do have it) and putting it all together in order to submit the application for Dengue Orphan Status to the FDA.

We should get the FDA approval for DengueCide® Orphan Status by September 2013 and another controlled/tracked race to the market will have begun. --- http://youtu.be/n4-uoUpN1c4 ---

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[1] biologics is a medicinal product such as a vaccine, blood or blood component, allergenic, somatic cell, gene therapy, tissue, recombinant therapeutic protein or living cells that are used as therapeutics to treat diseases. Biologics are created by biological processes, rather than being chemically synthesized.