Novavax’s clinical pipeline includes vaccine candidates engineered to elicit differentiated immune responses with potential to provide increased protection. Our recombinant nanoparticles and Matrix™ adjuvant technology are the foundation for groundbreaking innovation that holds the promise of improving immune responses and protection from traditional seasonal infectious disease and the threat of infectious pathogens with pandemic potential.
Respiratory Syncytial Virus F-protein nanoparticle vaccine candidate (RSV F Vaccine)
RSV is a widespread disease that causes infections of the lower respiratory tract. While RSV affects individuals of all ages, it acutely impacts infants, the very young, the elderly and others with compromised immune systems. RSV is the number one cause of hospitalization in infants ages 0 to 12 months in the U.S. and is a significant cause of infant morbidity and mortality globally 1 . Current estimates indicate that RSV is responsible for over 30 million new acute lower respiratory infection episodes and between 150,000 and 200,000 deaths in children under five years of age 2 . In the U.S., nearly all children become infected with RSV before they are two years of age; it has been associated with 20% of hospitalizations and 15% of office visits for acute respiratory infection in young children 3 . In addition, it is estimated that between 11,000 to 17,000 elderly and high risk adults die of RSV infection or its complications annually in the U.S., and up to 180,000 are hospitalized for serious respiratory symptoms 4 . The World Health Organization (“WHO”) estimates that the annual global disease burden for RSV is 64 million cases. Because there is no approved prophylactic vaccine, an RSV vaccine has the potential to protect millions of patients from this far-reaching unmet medical need.
Novavax is developing a respiratory syncytial virus F-protein nanoparticle vaccine candidate (RSV F Vaccine) for the benefit of three susceptible target populations: the elderly, infants (receiving protection through antibodies transferred from their mothers who would be immunized during the last trimester of pregnancy) and pediatrics.
RSV Elderly Program
In October 2014, Novavax initiated and completed enrollment in a Phase 2 dose-confirmation clinical trial of our RSV F Vaccine in 1,600 elderly subjects (>60 years of age). In May 2014, we released one-year follow-up data from the Phase 1 clinical trial demonstrating that palivizumab-competing antibodies (PCA) levels were significantly elevated over baseline at day 180, with neutralizing antibodies that were considered protective for both the RSV A and RSV B strains. We believe these findings support the development of an annual RSV F Vaccine dose that can provide protection over the four to five month period of a typical RSV season.
RSV Maternal Immunization Program
In September 2014, we initiated a Phase 2 clinical trial of our RSV F Vaccine in healthy women in their third trimester of pregnancy. This trial, which is designed to enroll fifty 50 subjects, will evaluate the safety and immunogenicity of our RSV F Vaccine in pregnant women and assesses the impact of maternal immunization on RSV-specific antibody levels through the baby’s first six months of life and infant safety through its first year of life. In November 2014, we announced that the FDA had granted Fast Track Designation to our RSV F Vaccine for protection of infants via maternal immunization. The Fast Track Designation, established by the FDA Modernization Act of 1997, is intended for products that treat serious or life-threatening diseases or conditions, and that demonstrate the potential to address unmet medical needs for such diseases or conditions. The program is intended to facilitate development and expedite review of drugs to treat serious and life-threatening conditions so that an approved product can reach the market expeditiously. Fast Track Designation specifically facilitates meetings to discuss all aspects of development to support licensure and it provides the opportunity to submit sections of a Biologics License Application (BLA) on a rolling basis as data become available, which permits the FDA to review modules of the BLA as they are received instead of waiting for the entire BLA submission.
In April 2014, we announced positive top-line safety and immunogenicity data from a Phase 2 clinical trial in women of childbearing age that were similar to, or exceeded, immune responses seen in our previous clinical trials. This Phase 2 clinical trial evaluated the safety and immunogenicity of two dose levels of our RSV vaccine candidate, in one or two injections, with and without an aluminum phosphate adjuvant, in 720 healthy women of childbearing age. These positive data supported Novavax’ decision to progress to a Phase 2 clinical trial in pregnant women.
PATH Vaccine Solution Clinical Development Agreement - RSV Maternal Immunization Program
In 2012 Novavx entered into a clinical development agreement with PATH, an international nonprofit organization, to develop our RSV F Vaccine candidate for maternal immunization in certain low-resource countries.
RSV Pediatric Program
While the burden of RSV disease falls heavily on newborn infants, RSV is also a prevalent and currently unaddressed problem in pediatrics. This third market segment for our RSV vaccine candidate remains an important opportunity. In November 2014, we initiated a Phase 1 clinical trial of our RSV F Vaccine designed to evaluate the safety and immunogenicity of our RSV F Vaccine in 150 healthy pediatric subjects two to six years of age.
Influenza is a world-wide infectious disease that causes illness in humans with symptoms ranging from mild to life-threatening, notably in susceptible populations such as, pediatrics and the elderly, but also because of unique strains of influenza for which most humans have not developed protective antibodies. Influenza is a major burden on public health worldwide; estimates of one million deaths each year are attributed to influenza 5 . It is further estimated that, each year, influenza attacks 5-10% of adults and 20-30% of children, causing significant levels of illness, hospitalization and death 6 .
Seasonal Influenza Vaccine
We believe our influenza virus-like particle (VLP) vaccine candidates have immunological advantages over current available vaccines. Our influenza VLPs contain three of the major structural virus proteins that are important for fighting influenza: hemagglutinin (HA) and neuraminidase (NA), both of which stimulate the body to produce antibodies that neutralize the influenza virus and prevent its spread through the cells in the respiratory tract, and matrix 1 (M1), which stimulates cytotoxic T lymphocytes to kill cells that may already be infected. Our VLPs are not made from live viruses and have no influenza genetic nucleic material in their inner core, which render them incapable of replicating and causing the disease.
In recent years, trivalent influenza vaccines (three influenza strains: two influenza A strains and one influenza B strain) have been made generally available on a worldwide basis. With two distinct lineages of influenza B viruses circulating, governmental health authorities have advocated for the addition of a second influenza B strain to provide additional protection and it is expected that quadrivalent seasonal vaccines will ultimately replace trivalent seasonal vaccines in the global market.
In November 2014, under our contract with HHS-BARDA, we initiated a Phase 2 clinical trial of our quadrivalent seasonal influenza VLP vaccine candidate in 400 healthy adults. The primary outcomes of the trial will assess safety and tolerability of the seasonal influenza VLP vaccine candidate and quantify immune responses to each of the four influenza strains based on hemagglutination-inhibiting antibody (HIA) titers. Secondary outcomes will evaluate neuraminidase-inhibition antibody titers for all four influenza strains.
Pandemic Influenza Vaccine
In the aftermath of the 2009 H1N1 influenza pandemic, recognition of the potential devastation of a human influenza pandemic remains a key priority for both governmental health authorities and influenza vaccine manufacturers. In the U.S. alone, the 2009 H1N1 pandemic led to the production of approximately 126 million doses of monovalent (single strain) vaccine. Public health awareness and government preparedness for the next potential influenza pandemic are driving development of vaccines that can be rapidly manufactured against a potentially threatening influenza strain. Until the spring of 2013, industry and health experts focused attention on developing a monovalent H5N1 influenza vaccine as a potential key defense against a future pandemic threat; however, a significant number of reported cases in China of an avian-based influenza strain of H7N9 have shifted attention to the potential development of an H7N9 influenza vaccine.
In collaboration with HHS-BARDA, we have developed and delivered compelling safety and immunogenicity data on two pandemic vaccine candidates, H5N1 and H7N9, which provide the U.S. government with alternatives for dealing with future potential threats. In September 2014, we announced positive results from a Phase 1/2 clinical trial of our H7N9 influenza VLP vaccine candidate adjuvanted with Matrix-M in 610 healthy adults. Under our contract with HHS BARDA, the Phase 1/2 clinical trial was designed as a dose-ranging, randomized, observer-blinded, placebo-controlled clinical trial, to determine the contribution of Matrix-M to potential antigen dose sparing regimens. In October 2014, we announced that the FDA had granted Fast Track Designation to our H7N9 VLP Vaccine with Matrix-M.
Health and Human Services –Biomedical Advanced Research and Development Authority (HHS-BARDA)
In 2011, Novavax entered into a collaboration with HHS-BARDA that supports the development of both our seasonal and pandemic influenza VLP vaccine candidates.
Combination Respiratory Vaccine (Influenza and RSV)
Given the ongoing development of our seasonal influenza vaccine candidate and our RSV vaccine candidate, we see an important opportunity to develop a combination respiratory vaccine. This opportunity presents itself most evidently in the elderly, although we have not ruled out developing a combination respiratory vaccine for the non-elderly. Early pre-clinical development efforts have given us confidence that such a combination vaccine is viable and in animal models, provides acceptable immunogenicity. We intend to explore this development opportunity by conducting a Phase 1 clinical trial in such a combination vaccine.
Vaccines for Emerging Threats
Middle East Respiratory Syndrome (MERS)
1 Dawson-Caswell, D, et al., (2011) Am Fam Physician. 83:143 - 146
2 Nair, H., et al., (2010) Lancet. 375:1545 - 1555
3 Hall, CB, et al., (2009) N Engl J Med. 360(6):588-98
4 Falsey, A., et al., (2014) Infectious Disorders. 12(2): 98-102
5 Resolution of the World Health Assembly. Prevention and control of influenza pandemics and annual epidemics. WHA56.19. 28 May 2003
6 WHO. Vaccines against influenza. WHO position paper – November 2012 Weekly Epidemiol Record 2012;87(47):461–76.