Influenza is a contagious and potentially fatal disease caused by a virus which infects the respiratory tract. Influenza viruses replicate in the cells lining the airways of the lungs and are generally spread directly to and from the respiratory tract by coughing and sneezing.
Influenza is typically characterized by the rapid onset of symptoms such as fever, chills, cough, sore throat, headache, muscle pains and extreme exhaustion. In the very young, the elderly and those suffering from chronic medical conditions, influenza may lead to pneumonia, severe complications of pre-existing diseases, hospitalization and even death.
Influenza can seriously affect anyone, but the people at highest risk of severe disease include young children, adults older than 65, and people of any age with underlying medical conditions, such as chronic heart, lung, kidney, liver, blood or metabolic diseases (for example, diabetes), or weakened immune systems.
Influenza spreads rapidly around the world in seasonal epidemics affecting between 5-15% of the population each year. According to the Centers for Disease Control and Prevention (CDC), in the U.S. alone, more than 200,000 people are hospitalized on average every year with influenza complications, and about 36,000 people will die because of the disease. The World Health Organization (WHO) estimates that annual influenza epidemics around the world cause between three and five million cases of severe illness, and between 250,000 and 500,000 deaths every year.
Influenza virus is changeable. As a result of minor genetic drift from year to year in circulating viruses a vaccine has to be changed on an annual basis and typically does not offer protection for more than a single season. Large, global epidemics called pandemics present a particular challenge and occur when the influenza A virus undergoes major genetic changes. The most infamous pandemic, the Spanish Flu in 1918-1919, killed 500,000 people in the U.S. and between 50 and 100 million worldwide, nearly half of whom were between 20 and 40 years old. The impact and frequency of pandemic influenza is inherently unpredictable but the risk of a serious pandemic has inspired global pandemic preparedness programs which include stockpiling of antiviral drugs, etc. The most recent pandemic occurred in 2009. Although by no means as severe as the 1918-19 pandemic and despite implementation of pandemic plans, including the use of stockpiled medication, the CDC has estimated between 2009 and 2010 there were approximately 61 million cases, leading to about 270,000 hospitalizations and approximately 12,500 deaths in the U.S. Notably, the use of antivirals as part of the pandemic response is estimated to have averted 8,000-13,000 hospitalizations in this population. Pandemic influenza can have a greater impact on different age and patient groups than seasonal influenza and a different disease progression. For example, in the 2009 H1N1 pandemic event some young and healthy people (eg. pregnant women) developed a severe form of primary viral pneumonia that is not typically seen during seasonal epidemics.
Influenza viruses are divided into groups A, B and C. Influenza A and B viruses are responsible for serious human disease including annual epidemics and, in the case of influenza A, pandemics whereas C is less common and causes a generally mild illness. Influenza A and B have two different spike-like protein components on their surfaces, called hemagglutinin (HA) and neuraminidase (NA). HA is responsible for attachment and infection of the host cell. NA is involved in the release mechanism the virus uses to subsequently shed from the lung cells.
NA is essential for the replication of all influenza A and B viruses. It is an enzyme which breaks down bonds that are holding new viruses to an infected cell, allowing viruses to be released and is likely to help the virus penetrate mucus. NA inhibitors block this activity, preventing the release of new viruses from infected cells and stopping the infection from spreading.
Biota originated the first NA inhibitor; zanamivir (marketed as Relenza®). Zanamivir (Relenza®) is delivered via an inhaler directly to the site of action, in the lung. By using this targeted delivery Relenza® is able to exert its antiviral effect very rapidly exactly where it is needed. Because targeted delivery allows a reduced dose and lower exposure to other organs it also reduces risk of systemic side effects.
Biota's second generation influenza products are long-acting neuraminidase inhibitors (LANIs). The "long acting" feature of the LANIs is designed to allow a unique once weekly or once only inhaled dosing profile which provides a big advantage over the twice daily doses required for first generation NA inhibitors.
LANI's high potency and reduced frequency of administration is particularly attractive for pandemic stockpiling and offers significant benefits for use during epidemics and pandemics. Biota and Daiichi Sankyo have cross-licensed intellectual property related the development and commercialization of LANIs. The lead LANI, known as laninamivir octanoate has completed clinical development in Japan and is marketed by Daiichi Sankyo as Inavir®.
In April 2011, Biota announced it had been awarded a contract from the Office of Biomedical Advanced Research (BARDA) within the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS) for up to an estimated US$231 million. The contract is designed to provide U.S. based manufacturing and for completion of clinical development. It is planned to culminate with a New Drug Application for laninamivir octanoate to the Food and Drug Administration for treatment of influenza A and B infections. The Company anticipates initiating a 636-patient, randomized, placebo-controlled Phase 2 clinical trial of laninamivir octanoate in mid-2013.