Money for something in RSV

GAITHERSBURG, Md.—A vaccine for one of the most common sources of respiratory tract infections may finally be on the horizon, with good news on both the preclinical/animal model and human clinical research fronts. In two separate mid-stage clinical trials ,the vaccine development company Novavax has found success at immunizing pregnant women and elderly patients with a vaccine for respiratory syncytial virus (RSV), an infection that primarily affects infants, the elderly and those with compromised immunized systems. Shortly after Novavax’s data from the study were released this fall, the company announced it had received an $89-million grant from the Bill & Melinda Gates Foundation to support Phase 3 trials of the vaccine in pregnant women.

 

This followed closely on the news in mid-September that its RSV F-protein recombinant nanoparticle vaccine candidate was shown to be highly immunogenic in a guinea pig model of maternal immunization.

 

“RSV is the leading cause of infant hospitalizations in the U.S. and a significant unmet need in full-term infants,” said Dr. Gregory M. Glenn, senior vice president of research and development at Novavax, of the animal study. “The placental architecture in guinea pigs reflects the anatomy found in humans, making them an appropriate model to evaluate placental transfer of antibodies. These preclinical data further support our RSV F vaccine maternal immunization program, and we look forward to announcing data from our Phase 2 clinical trial to protect infants via maternal immunization this quarter.”

 

That Phase 2 data, of course, as already noted above, has proved fruitful.

 

Currently, there is no vaccine for RSV, which is estimated to cause 57,000 hospitalizations of children under age 5 in the United States each year. The MedImmune drug palivizumab, a monoclonal antibody, is sometimes used to prevent RSV, but it is a relatively expensive treatment and is generally only used with very limited populations at high risk, such as premature infants.

 

Novavax has for many years been working to develop a vaccine inspired by the mechanism of action that makes palivizumab effective. Novavax’s vaccine under development targets the same F-protein that palivizumab targets. For this reason it is referred to as the RSV F vaccine.

 

Novavax is developing its vaccine to benefit three populations vulnerable to RSV: older adults, infants and pediatrics. “To date, we’ve run six clinical trials and across all of the participant populations in those trials we’ve showed a consistently robust immune response,” Barclay Phillips, CFO of Novavax, tells DDNews. “And we’ve also established a very robust safety profile.”

 

The $89-million grant from the Gates Foundation will be directed specifically for the late-stage trials of a vaccine for infants, which Novavax is developing to deliver through maternal immunization. It is difficult to directly immunize infants due to their immature immune systems that are unable to fight off viral infections. Fortunately, mothers transmit antibodies to their offspring through in-utero transplacental transfer of immunoglobulin G antibodies.

 

“If we immunize the mother and her immune system creates robust response, the mother will actually transfer her immune response through the placenta to infant,” Phillips says. “So that infant will be born with bolus of antibody that will protect them from infectious organisms.”

 

Novavax’s recent Phase 2 trial of this RSV F maternal immunization involved 50 pregnant women in their third trimester. The study found that those who received the vaccine had increased levels of antibodies, while those on a placebo had no significant change. Similar results were found in the babies of those mothers. Infants whose mothers had received the vaccine had elevated levels remaining in their bloodstream. The company said the data from the study was consistent with immune responses observed in previous trials in women of child-bearing age.

 

Phillips tells DDNews that the grant from the Gates Foundation will fund a significant portion of its upcoming Phase 3 trials, which will take place in both the Northern and Southern hemispheres to reflect the seasonal nature of the virus. In exchange for the funding, Novavax is promising to take steps to ensure that the vaccine reaches the developing world. The company has agreed to provide the vaccine—if it proves successful and becomes commercialized—at a discounted cost in certain developing nations where it would otherwise be out of reach for the vast majority of the population.

 

“RSV is the leading cause of pneumonia in infants, and currently there are no affordable approaches to protecting children in the developing world from this viral disease,” said Dr. Keith Klugman, director of the Bill & Melinda Gates Foundation’s Pneumonia Program, in a statement released to the press. “Maternal immunization may provide protective antibodies to infants during the first few months of life, and we hope this vaccine will protect infants from this disease to help them live healthy, productive lives.”

 

One key question that Novavax is attempting to answer in its preclinical trials is how long immunization passed on from mothers remains active in the infant. “We know that the antibody has a certain life cycle in the infant, so the question is how long will a relevant level of those antibodies offer protection,” says Phillips. “At least in the preliminary assessments, findings suggests that antibody protection of three to four months, and that timeframe is the period during which the majority of hospitalizations due to RSV occur in the U.S.”

 

Novavax has also released positive findings in recent months from Phase 2 trials focused on the use of the RSV F vaccine in adults age 60 and older. The study, which involved 1,600 participants at 10 sites in the U.S., found that the vaccine achieved statistically significant efficacy in prevention of all symptomatic RSV disease that was similar to or better than multiple recent effectiveness estimates for licensed respiratory vaccines tested in older adults for pneumococcal and standard-dose seasonal influenza.

 

“These efficacy data represent a historic advance for the field,” said Glenn in a statement announcing the findings last August. “This is also an important confirmation of the burden of RSV disease in older adults and highlights the high rate of lower respiratory tract symptoms in those infected by RSV in a large, prospective trial. It is clear that our RSV F Vaccine provided statistically significant efficacy in older adults, a population that historically has been difficult to protect.”