NanoViricides, Inc. (the "Company") announced today that the European Medicines Agency (EMA), has awarded orphan drug designation to DengueCide™, the Company’s drug candidate for the treatment of dengue and dengue hemorrhagic fever.
Dengue Fever is a mosquito-borne disease that, according to the WHO, affects approximately 400 million people per year. Dengue Hemorrhagic Fever, a subset of the disease that can occur after reinfection with another strain of the same virus, has a case fatality rate of up to 20%.
This orphan drug designation enables several benefits for the Company’s dengue drug development program. These benefits include “protocol assistance,” or specific scientific advice that can speed up the drug development program, as well as certain fee reductions, for drug approval(s) under EMA.
More importantly, an approved orphan medicine in the EMA countries is expected to benefit from ten years of marketing exclusivity protection. An additional two years of exclusivity can be obtained if the drug development has complied with an agreed pediatric investigation plan, with a total of twelve years of market exclusivity for a drug that is approved for both adult and pediatric usage. Further information on the incentives offered can be found at the EMA website http://www.ema.europa.eu.
Applications for orphan designation are examined by the European Medicines Agency's Committee for Orphan Medicinal Products (COMP), using a network of international experts. This designation is recognized by all 27 countries within the European Union.
The Company has previously reported that DengueCide was awarded orphan drug status by the US FDA. The Company has also recently reported the renewal of its evaluation agreement for DengueCide and next generation dengue therapeutics with the Dr. Eva Harris Laboratory at the University of California, Berkeley.
In the USA, orphan drug designation qualifies NanoViricides for certain tax credits and marketing incentives under the Orphan Drug Act. In addition, the Company will qualify for the waiver of certain FDA fees if and when it files the New Drug Application (NDA) for DengueCide with the FDA. Further, the Company will also be eligible for a “Priority Review Voucher” (PRV) from the US FDA when the Company files a NDA for DengueCide.
“Our dengue drug development programs have been accelerated in order to take advantage of these benefits,” said Eugene Seymour, MD, MPH, CEO of the Company. DengueCide is in pre-clinical development at present. If the pre-clinical development is successful, the Company will need to file an “Investigational New Drug” (IND) application to the US FDA and perform human clinical trials. If the human clinical trials are successful, then the Company has to file a NDA to the FDA to obtain approval to market the drug. There is no guarantee that DengueCide will successfully result in an NDA or a marketable drug product.
If the Company receives a Priority Review Voucher, it can be applied to accelerate the review of another one of our own drugs or it can be sold to another pharmaceutical company for a consideration. Priority review means that the FDA aims to render a decision on the NDA in 6 months. In contrast, the FDA aims to complete a standard review in about 10 months, and it often takes even longer. The estimated economic value of a PRV depends upon the drug class, and could be as high as a few hundred million dollars, according to Duke economists (Ridley et al. 2006; Grabowski et al. 2009). (https://faculty.fuqua.duke.edu/~dbr1/voucher/).
The Company engaged the consulting firm Coté Orphan Consulting (COC), headed by Dr. Tim Coté, to assist with our DengueCide orphan drug applications to both the US FDA and the EMA.
DengueCide is a nanoviricide® that has shown very high effectiveness in an animal model of dengue virus infection. These animal studies were conducted in the laboratory of Dr. Eva Harris, Professor of Public Health and Infectious Diseases at the University of California, Berkeley. Professor Harris has developed a mouse model of antibody-dependent-enhancement (ADE) of dengue infection that simulates dengue hemorrhagic fever (DHF/DHSS) using a special laboratory mouse strain called AG129. In humans DHF/DHSS is associated with a high fatality rate. In this model, infection with a dengue virus, when the mice are left untreated, is 100% fatal. In contrast, in the same study, animals treated with NanoViricides' DengueCide achieved an unprecedented 50% survival rate.
There is currently neither an effective drug treatment nor a vaccine for dengue virus infection. No vaccine or drug candidate has succeeded in clinical trials towards approval as of this date in spite of significant development efforts. Several dengue virus vaccine clinical trials are ongoing. Previously, a drug called poly-IC-lC received an orphan designation in 2003 for dengue treatment in the USA. This drug is supposed to act as an immune booster and is in several clinical trials. Three additional treatments for dengue fever are found in a search of the clinical trials database (http://clinicaltrials.gov/ct2/results?term=dengue&pg=5&show_xprt=Y). These include chloroquine, balapiravir (Roche), and celgosivir.
The Company continues to advance its injectable and oral FluCide™ broad-spectrum anti-influenza drug candidates towards clinical trials. Both of these drug candidates have shown extremely high effectiveness and substantial superiority to Tamiflu®, the standard of care, in the unrelated influenza virus types H1N1 and H3N2 in a high lethality animal model.
About Dengue and Dengue Hemorrhagic Fever
Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyper-endemicity (the co-circulation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 2013, this mosquito-borne disease is one of the most important tropical infectious diseases globally, with an estimated 400 million cases of dengue fever, over one million cases of dengue hemorrhagic fever, and 50,000-100,000 deaths annually. Dengue virus occurs in four primary serotypes although a fifth serotype has been reported recently in Indonesia. There have been recent outbreaks in both Florida and Texas. Puerto Rico had 30,000 cases of dengue this past summer. For the first time, the mosquito vector, Aedes Aegypti has also been found in California. Although the disease is endemic in many tropical parts of the world, it is considered an orphan disease in the USA and Europe. (From Clinical Microbiology Reviews).
NanoViricides is developing broad-spectrum anti-influenza drugs as part of its rich drug pipeline. The Company believes that its FluCide™ drug candidates will be effective against most if not all influenza viruses, including the H7N9 bird flu, H3N2 or H1N1 epidemic viruses, H5N1 bird flu, seasonal influenzas, as well as novel influenza viruses. This is because FluCide is based on the Company’s biomimetic technology, mimicking the natural sialic acid receptors for the influenza virus on the surface of a nanoviricide® polymeric micelle. It is important to note that all influenza viruses bind to the sialic acid receptors, even if they rapidly mutate. The FluCide drug candidates have already shown strong effectiveness against H1N1 and H3N2 influenza viruses in highly lethal animal models. The injectable FluCide drug candidates have shown 1,000X greater viral load reduction as compared to oseltamivir (Tamiflu®), the current standard of care, in a highly lethal influenza infection animal model. The Company believes that these animal model results should translate readily into humans.
NanoViricides has also developed an oral drug candidate against influenza. This oral version is also dramatically more effective than TamiFlu in the animals given a lethal influenza virus infection. This oral FluCide may be the very first nanomedicine that is effective when taken by mouth. In addition, NanoViricides has developed drug candidates against HIV/AIDS, Herpes, and Ocular Viral Diseases that have shown strong effectiveness in relevant animal and/or cell culture models.
About Cote Orphan Consulting - Expertly Guiding Orphans Through the FDA
COC was established by Tim Coté, MD, MPH, as a consulting service to pharmaceutical companies working in the area of rare and neglected diseases. Dr. Coté 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. He served as the Chief Medical Officer (CMO), National Organization for Rare Disorders (NORD), Washington, DC, after leaving the US FDA. 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. He is currently Professor of Regulatory Practice at the Keck Graduate Center, Claremont, CA, in addition to his role as the Principal at COC.