Novavax’s Robinson: Taking Vaccines to the World

JR: We compare our vaccines today based on the same amount of HA going into a dose. Ours shows the same or better immunogenicity than licensed product, but the only thing we can really compare with licensed product is hemagglutinin, which is 40% of our vaccine…the remaining 60% is made up of neuraminidase and matrix proteins both of which are highly conserved in flu (theydon’t change much as the strains change from year to year). We believe this will contribute to protection, but there’s nothing to compare those two components to.  In a way, we’re at a disadvantage because we can only measure the protective nature of one of our component proteins although we know historically that the other two will confer some level ofprotection.

In immunogenicity studies, which are how you license flu vaccines today, we are comparable.  In efficacy we believe we will be superior, but those studies are costly and may be part of our initial licensing.

PhM: Are you planning to partner with any pharma companies?

JR: We’re a small biotech and there are ways to get vaccines licensed by following the immunogenicity model, which costs about $50 million, but, eventually you want to do both immunogenicity and efficacy.

If we were partnering with a big pharmaceutical company, they would likely want to invest in efficacy studies because positive results would differentiate the product, giving it a marketing advantage. The market is already crowded. Currently, there are six or seven licensed vaccines, and each year more and more vaccine is being left unused, which will eventually drive people to price cutting, driving market value down. This could cause the market to collapse so that nobody wants to be in it again. We’ve been there before.

In addition to the clinical study cost required to license a product, there is also a tremendous amount of work in product characterization, process and analytical validation, quality system development, and infrastructure development that would certainly benefit from the help of a larger Pharma partner or collaborator.

PhM: What are the operating costs relative to those of traditional vaccines?

JR: About a year ago, we had demonstrated the yields to be less expensive than egg-based flu, which is more productive than cell based.  We believe that we will be the least expensive technology for flu vaccine manufacturing. However, it takes many million dollars to get licensed, so you have to consider what would be a fair rate of recovery of that investment. Then there’s the cost of setting up and underwriting all your capital, and the business risk involved.  You need to put a lot of money in before anything comes out.  Because of this its hard to say what the full cost of production will be relative to other established products, but we are confident it will be competitive.
 
It could also be a better product--we have yet to see results from clinical studies. We haven’t done a full-scale production study yet, but, if everything pans out, we will know the benefits of our vaccine as well as the cost.

PhM: What types of adjuvant are you evaluating?

JR: We’re not using adjuvants, although a lot of other companies use them to stretch antigen for pandemic, or to increase immune responses in older populations, One way to get a stronger and more cross-protected response is to use adjuvant, but it is also important to know if that higher response is specific to flu. The concern is what adjuvants do to human immune system after repeated use? Does it, after several years of using adjuvant, completely overwhelm the immune system to a point where it won’t respond anymore? Then you’d have a population that was once at risk that can’t be protected where at least you can give them some protection today.  I am not an immunologist by any means; this should be heard as a layman representing his understanding of the issues that are discussed extensively in many global meetings on influenza vaccine development and testing.

This is really a concern to FDA. Regulators are concerned about the fallout if they approve anything that turns out to be unsafe, not just out of concern for individual patients, but because of the current anti-vaccine climate.  If people stop believing in vaccines (there are already enough people that don’t get vaccinated who should. And  that has caused outbreaks of measles and other diseases).and yet there are enough anti-vaccine people who are trying to reduce the uptake of vaccine, FDA doesn’t want to put out any vaccine out there that has an unacceptable level of risk.

In the event of pandemic, for example, if it were H5N1, where mortality is as high as 80% of people infected, one would take the risk and use with adjuvant because it would be more important to protect people from immediate danger.

H1N1 does not have high mortality (although it’s highly infectious), so perhaps FDA doesn’t think it’s worth the risk of putting anything on the market without adequate safety data.  At this point, we do not plan to use adjuvant, although we do have adjuvant data in development, and our vaccine, when used with adjuvants, looks better than existing ones.  We’ll reserve its use as a backup plan.

PhM: Over the years, we have heard of so many quality disasters at vaccine plants. Are there any potential QA/QC risks with your system?

JR: There’s a lot of inherent risk in making flu in eggs. I think the most recent experience in reacting to the H1N1 pandemic shows the need for improvement of the technology for making flu vaccines. 

Chicken eggs are far from the ideal substrate for making a vaccine, but they have produced many billions of doses of vaccine that have protected many millions from disease while the new vaccines are being developed. Specific release tests for endotoxin and sterility are used to ensure that the egg-based process is safe and under control; but our process does not use a pathogenic organism (e.g., the flu virus)and it is free of biological contamination associated with eggs. Many of the risks with traditional systems are eliminated and others are minimized with the use of single-use systems. Of course we also have to manage the supply of our single-use components and suppliers to avoid an unplanned interruption in supply. However, managing those issues are expected to be a little less involved than managing the supply of 600,000 eggs per day.

In my professional life, I have probably made about 600 million doses of influenza vaccines in eggs; “the hard way”. This technology has many advantages in time, cost, expandability, and potentially protection, but it is expected to be safer, from both a manufacturing and a patient viewpoint as well.