Transmitted by the same mosquitoes that spread Zika virus and dengue fever, the chikungunya virus is named for an African word meaning “to become contorted.” People infected with the alphavirus are afflicted with lasting joint pain that causes their backs to hunch over, according to the World Health Organization.
The virus, which has cropped up in Africa, Asia, Europe and the Caribbean, has no vaccine. Instead, the Centers for Disease Control & Prevention recommends that people traveling to countries with chikungunya virus use insect repellent and wear long sleeves and pants.
But Nima Farzan thinks a vaccine in his company’s pipeline could help change that.
The candidate was first developed at the NIH, where it was evaluated through a Phase IIa trial. Farzan’s company, PaxVax, in-licensed the product and is gearing up for 400-person Phase IIb study.
“The NIH’s approach was to go in and test it in clinical trials to see if there was safety and immunogenicity. They demonstrated that. But they had a process that was frozen and done at a lab scale – it was done at a 20-liter scale,” Farzan told Drug Delivery Business News. “So we spent a lot of time scaling it up, working on the formulation, purification – everything you need to be able to produce reliably and consistently at large scale. Now, we’re taking that forward into a Phase IIb.”
The company plans to conduct a dose-finding and regimen optimization study, assessing how often the product needs to be administered.
“The Phase IIa study was two doses, four weeks apart. What if we shorten the time between the doses? Could we still get the same response? What if we had a single dose? Could we still get the same response? What if we added alum as an adjuvant? Would that give us a better response? It’s really all about optimization, finding the minimal effective dose and the most effective and efficient dosing regimen,” he explained.
The vaccine, which PaxVax is developing in partnership with the NIH and the U.S. Dept. of Defense, makes use of virus-like particles, Farzan said. The goal is to create a product that can be efficiently administered in countries with limited resources.
“The ideal vaccine is single dose. Single dose, oral would be nice but injectable is acceptable. You would not want it to be reconstituted, to simplify the process for the offices. And you’d want it to be refrigerated [rather than frozen]. Some will say room temperature would be ideal, but we don’t have any room temperature vaccines today. So, realistically, you’re looking for a single dose, refrigerated, oral or prefilled syringe,” Farzan said.
There are immense challenges in developing vaccines for epidemic diseases, he noted. As demonstrated by the nightmarish Zika virus outbreak in 2016, sudden outbreaks of aggressive viruses can tear through communities since there is no established immune response.
“No one is immune to it, so everyone’s susceptible,” Farzan said. “You get this huge outbreak which makes the news and then, of course, the outbreak burns itself out a bit. Then you get a low-level endemicity of disease and in six or seven years when that immune response has waned and you have a new cohort of people who aren’t immune, you’ll get another outbreak.”
There are other challenges in developing vaccines to tackle diseases like chikungunya and dengue fever.
“These are often diseases of the developing world,” Farzan said. “They’re vaccines for niche populations and there hasn’t been a company that has the capabilities to do the R&D and the manufacturing and the commercialization but is also nimble enough and small enough to focus on those overlooked diseases.”
But as chief executive, Farzan sees PaxVax as doing just that. The company has two commercial products: a vaccine for typhoid fever that is available in several dozen countries, including the U.S., and a vaccine for cholera, which is only available in the U.S.
The company has encountered its own set of challenges in developing these two products. With its typhoid fever vaccine, PaxVax produces more than 1 million doses per year.
“So you can imagine the scale and the consistency of processes [that’s required],” Farzan said. “Vaccines are biologics and in some cases, when we’re talking about live-attenuated vaccines, we’re actually delivering a live organism, so it’s pretty complex.”
When PaxVax won approval for its cholera vaccine in June of 2016, the company was producing it at a 200-liter scale and the product was frozen – a formulation that Farzan described as “less than ideal.”
“We didn’t have the time or the money to spend several extra years improving on those characteristics. When you’re small, the goal is to get the product to market as soon as you can before you run out of money. So we went quick,” he said. “Now that we’ve gotten approval, we’ve spent the last two years going back and revisited it. Now, we’ve scaled up the process to 3000 liters and we have a refrigerated product.”
The company is preparing for a big year – Farzan is hopeful that its chikungunya vaccine, which won fast track status with the FDA in May, will be ready for a pivotal Phase III trial.
Farzan is aware of the competition looming from larger, well-funded pharmaceutical companies, but he believes his company differentiates itself with its focus.
“There is a handful of ‘Big Pharma’ companies that are doing vaccines and obviously they’re fully integrated – they’re doing R&D, manufacturing, sales and marketing. But they have been focused on very large opportunities,” he said. “Where we see our advantage is there’s a whole set of overlooked diseases. Diseases that maybe there could be a vaccine for, but they just haven’t been focused on by the big pharma companies because the opportunity may not be big enough.”
“We’re trying to build a vaccines company and a vaccines business,” he added.
Steve MacMillan took over as CEO of Hologic in 2013, drawing on his experience at medtech titans like Stryker and Johnson & Johnson. Since then, Hologic has grown into a $3 billion business.
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